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Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach.
Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment.
A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed.
Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation.
In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target “large” dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication.
Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment administered systemically or intrathecally (10%) and thus all other conventional methods to find relief [1-3]. Current pain management with opioids especially at the high amounts that might be needed as breakthrough, or rescue doses is associated with important secondary effects that include gastrointestinal symptoms, respiratory depression, and lethargy. Since its origin, radiosurgery was conceptualized and has been used for pain relief in non-oncological and oncological pain with various success rates, the classical approaches have been single target and a few dual target irradiation using ablative doses (>130 Gy) to achieve different degrees of pain relief [4-14]. For bone-derived pain, mainly in hormone-mediated cancers such as breast and prostate, a high dose of radiation to the hypophysis has been described as successful in most patients (>70%) [7-11,14]. In our experience, this approach may not be as effective in abdominal or pelvic pain from histology such as ovarian and pancreatic cancer or neuropathic pain derived from brachial plexus involvement in Pancoast syndrome . Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric and/or central mediated pain circuitry, ideally with a sub ablative dose, although the clinical importance of lesser doses in oncological pain in terminally ill patients remains to be proven.
Recently our group published a novel, dual-target approach for pain crisis management in trigeminal neuralgia where all other approaches had failed, the main objective of this approach was to consistently provoke radiomodulation. The dual targets irradiated were the affected trigeminal nerve with 90 Gy and the contralateral structures of the medial thalamus, which encompass in part the perifascicular complex (PFc) and centromedian nucleus (CM) with 140 Gy, a dose considered ablative. In this communication, the last patient treated with success was using a dose of 80 Gy to the nerve and 120 Gy to the thalamus, in this series radiomodulation was achieved in 100% of the population leading to pain relief of at least 50% in less than 72 h . More recently, patients have been treated with 80 Gy to the nerve and 90 Gy to the thalamus with the same success [unpublished data], demonstrating that lower doses could be effective when multi-target radiosurgery is performed for pain.
We present preliminary clinical evidence in three patients with refractory pain that were treated with triple target irradiation with what might be considered low doses of radiation in comparison to the more traditional single target, ablative dose approach.
Materials & Methods
From January to March 2022, three terminally ill oncological patients experiencing mixed pain from bone, abdomen, thorax, and brachial plexus, refractory to opioids were treated with triple target irradiation. This approach consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (CK) (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. These patients were referred by palliative and pain medicine specialists as they were deemed refractory to all other treatments available and despite best efforts, their perceived pain scale was 10 in the visual analogue scale (VAS). Their cases were discussed and approved by a multidisciplinary team of algologists, radiation oncologists, and neurosurgeons. All patients and caregivers signed informed written consent. This treatment protocol was approved by the International Cancer Center Group ethical committee board. We correlate the isodose curves of 45 Gy and 20 Gy of two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia, for further understanding of dose distribution three-dimensional reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed, lastly, we carried out a review of the literature of radiosurgery for oncological pain.
On the day of the procedure, under local anesthesia and slight sedation a stereotactic frame was placed by a neurosurgeon with the aid of ear bars searching for a frame parallelism to the anterior and posterior commissure line or the intercommissural line (ICL) for the Infini. For CK a thermoplastic mask was configured seeking the ICL parallelism with the CT lasers. For Inifni an MRI acquisition was performed with a 1.5-Tesla Avanto (Erlangen, Germany: Siemens Corporation) of the full head, a T1 and T2 constructive interference in steady state of 1 mm slice thickness with no spacing covering the thalamus until the superior border of the corpus callosum; for both patients treated with CK they were implanted with intrathecal or peripheral drug delivery pumps that made MRI studies not possible thus CT of 0.625 mm thickness with no spacing was done of the whole head including the jaw. Images were later transferred to the treatment planning stations (Superplan for Infini and Multiplan for CK). For treatment planning, the anterior commissure (AC) and posterior commissure (PC) were identified in the axial plane, then images were transformed into a sagittal plane using fusion tools and the ICL was drawn. The distance from the PC was taken anteriorly along the ICL (usually 4 mm); this measure was tagged as Y. A 90º angle was traced from the PC to the Y along the ICL and Z was determined usually 4 mm above the ICL. Images were then reoriented to axial views, and X coordinates were 4 to 5 mm lateral from the thalamic border on each side. Using a 4 mm collimator with Infini and a 5 mm cone with CK, a single shot was placed in each region of the thalamus prescribing 90 Gy as Dmax bilaterally, the 20 Gy isodose line was plotted as a possible “area of influence” of radiation (Figure 1).
For the hypophysis target efforts were made to identify the neurohypophysis and define this as the isocenter of the shoot, using an 8 mm with Infini and a 7.5 mm collimator with CK 90 Gy Dmax was delivered, the complete optic pathway and brainstem were defined as an organ at risk so that in any case the dose would not be superior to 8 Gy in the optic pathway or 15 Gy at a focal point in the brainstem. For the CK the plan was isocentric with 90 Gy to 97% using a short path and Monte Carlo algorithm at high resolution for dose calculations, as it is standard for this machine 6D skull tracking was used.
Patients were contacted 24, 48, 72, and 96 h after treatment and every week thereafter until the time of death. Radiomodulation effect was defined as a prompt relief of pain (reduction in VAS of at least 50%) specifically within the first 72 h after stereotactic radiosurgery (SRS). Morphine rescue as an additional parenteral administration of morphine over the basal needs of pain medications was considered a more objective indicator of pain relief. Patients were asked to level their pain during every follow-up call and to report any increase in pain not responding to their usual medication as well as the amount of morphine rescues required per day.
For Infini and CK, isodose correlation was approximated as much as possible to the Anne Morel stereotactic atlas of the thalamus and basal ganglia (Morel atlas) by measuring the anterior to posterior diameter of the 45 and 20 Gy isodose line as well as its medial to lateral diameter, distance from the thalamic border (TB) was considered in reference to the isocenter of the shoot that was 4 mm anterior to the posterior commissure, for the CK due to its irregular shape the maximal distance from the TB to the 45 and 20 Gy isodose lines was considered as well as the distance from the TB to the most anterior and posterior point and extrapolated to the atlas. With regards to cephalocaudal (Z) direction from the anterior commissure and the posterior commissure (ACPC) line, Infini was taken every 1 mm and for CK every 1.25 mm and correlated to the closest image on the atlas (Figures 2-5).
For an additional validation and greater three-dimensional comprehension of the areas affected by radiation, thalamic nuclei were segmented according to Hassler's cytoarchitectonic criteria in histological plates and registered into a post-mortem MRI and normalized to a stereotactic space (ICBM 152 MNI space) as part of the São Paulo-Würzburg atlas of the Human Brain Project. The average coordinates of the isodose correspond to the 45 Gy and the 20 Gy isodose line for the Infini and the 45 Gy isodose line for the CK were centered and plotted into the histological atlas to illustrate the structures affected by radiation, the 20 Gy isodose line for CK could not be accurately reconstructed due to its irregularities in comparison to the Infini (Figures 6, 7).
Review of literature
Lastly, we carried out a review of the existing literature to date regarding the use of stereotactic radiosurgery for the treatment of oncologic intractable pain. PubMed was the primary database for electronic article searching using the medical subject headings (MeSH) terms “radiosurgery” AND “intractable pain”; there was no restriction on language or publication date; publication dates ranged from 1970 to 2022. Peer-reviewed articles reporting clinical outcomes and containing follow-up information regarding the safety of SRS for oncologic pain targeting either the pituitary gland and/or thalamus were considered inclusion criteria; precise target definition was also an important aspect to consider. Cases where radiosurgery was performed due to chronic pain originating from trigeminal neuralgia or other cranial nerve neuralgia and where SRS was used for other conditions than pain were excluded. Follow-up time was not a criterion for exclusion given the prognosis of the disease in patients included in this series. After title and abstract reading, only 14 studies remained eligible for full-text evaluation and after full-text reading, only nine studies met with inclusion criteria (Figure 8). Table 1 summarizes our findings regarding pituitary and/or thalamic radiosurgery for the management of oncologic intractable pain.
The first patient was a 65-year-old Latin male with known hypertension and benign prostatic hyperplasia. The patient was being studied for an unknown metastatic disease that proved to be a pulmonary adenocarcinoma. When the patient was referred to our center in February 2022, he presented with thoracic and lumbar metastatic pain, as well as pain in the hips and lower extremities, he could not adopt a supine position since November 2021 due to intolerable pain. Regarding previous therapeutic interventions, he had gone through radiofrequency (thoracic T10, T11, T12 and lumbar L3, L4, L5, S1) bilaterally, T11 vertebroplasty due to a pathologic fracture as well as stereotactic body radiotherapy (SBRT) with a dose of 24 Gy in three sessions (8 Gy per fraction) but was considered non-effective in either ameliorating pain or decreasing the amount of medication used. Baseline treatment for pain included extended-release morphine 30 mg every 8 h, paracetamol 750 mg every 8 h, ketorolac, and rescue morphine up to 12 times a day. Daily pain reported was VAS of 10 and after rescue morphine, he reached VAS of 3 but the effect only lasted between 30 minutes and 1 h.
The second patient was an 18-year-old Latin female with a relapsing Ewing sarcoma. She went through surgery for tumor resection in her left hemithorax along with chemotherapy and adjuvant radiotherapy (3D technique) to the tumor resection site receiving 54 Gy in 27 fractions. A second radiotherapeutic session of 8 Gy/1 fraction at a supra and infraclavicular level was delivered in April 2021 with a palliative intention due to tumor recurrence and increasing amounts of pain. In November 2021, a third radiotherapeutic session using lattice technique was given to the recurring left hemithorax mass, and in this case, two targets were considered: planning target volume (PTV)1 (whole mass) receiving 9 Gy/3 fractions and PTV2 (mass vertex) receiving 24 Gy/3 fractions; only partial relief of pain was achieved. During progression, the patient was referred to our center because of increasing pain in her shoulder, left arm, and left chest wall due to extensive intrathoracic tumor growth and malignant brachial plexopathy.
Previous pain treatments included multiple brachial plexus blocks with local anesthetic, steroids, botulinum toxin, and considering multifocal pain distribution she had a tunneled continuous interscalene brachial plexus and an epidural catheter at T5 delivering local anesthetic. The patient required a continuous IV morphine infusion (285 mg daily), 15 mg boluses as needed every 2 h, 1800 mg daily gabapentin, and venlafaxine 75 mg. She was considered unfit for implantation of an intrathecal drug delivery system. Despite multimodal analgesia, the patient had a VAS of 10 and continued need of rescue morphine to achieve a VAS of 5.
The third patient was a 66-year-old Latin male with stage IV pancreatic adenocarcinoma metastatic to liver, peritoneum, and bone. In June 2021, he received palliative radiotherapy to the dorsal spine (25 Gy/5 fractions), but response to treatment was only partial. The patient was referred to our center in March 2022 due to refractory oncologic pain presenting at an abdominal, thoracic, and lumbar level. Baseline pain treatment for this patient included an intrathecal pump (Synchromed II; Minneapolis, MN: Medtronic) delivering morphine 4.6 mg/24 h and bupivacaine 1.5 mg/24 h, 100 ug/h transdermal fentanyl, and intrathecal morphine rescue every 2 h through a patient controller (average of 12 rescues per day). A previous celiac plexus neurolysis was performed but deemed unsuccessful.
Patient 1 was followed at 24, 48, 72, and 96 h after treatment and every week thereafter. At 24 h, he reported a VAS of 7 and required only three morphine rescues, at 72 h his VAS had decreased to 4 and required only two morphine rescues (only 16% of requirement). Six days after treatment the patient had pulmonary thromboembolism, which required hospitalization; during his hospital stay, he tolerated a supine position at 30 degrees without any sedation or morphine rescues. The blue line shows the VAS progression of patient 1 during the first 96 h (Figure 9) and after treatment and until his death (Figure 10).
Figure 11 shows the number of rescues needed per day after SRS. During these 21 days, his VAS varied between 0 and 5, and his pain responded to baseline treatment, decreasing the number of morphine rescues he usually required; from 12 morphine rescues in a day, he was then able to spend a day without any rescue requirements to reduce pain (84% reduction in morphine rescues).
Patient 2 is represented as the orange line in Figures 9-11. At 24-h follow-up, her VAS was 8 and required only three morphine rescues (25%). Forty-eight hours after treatment, her VAS had reached 4 and only 16% of her basal morphine rescues were required. During her follow-up, the patient reported up to four days without any need for morphine rescues (0%) with only baseline treatment ameliorating her pain; other days she reported pain crisis, reaching VAS of 7 but responded to baseline treatment or required only small amounts of morphine rescues (16%). The patient died 29 days after treatment due to primary disease progression and an allergic reaction to chemotherapy; her need for morphine rescue was reduced by 84% during this period.
Patient 3 is represented by the gray line in Figures 9-11. Twenty-four hours after SRS, the patient reported a VAS of 7 requiring only two morphine rescues. At 72-hours, he had a VAS of 4 and needed only one morphine rescue. The first eight days after SRS, VAS varied between 3 and 6 and reported feeling more sleepy than usual. At his next follow-up, his VAS increased between 6 and 9, but his morphine needs were between 16% and 41%, never requiring the initial dose to manage the pain crises. VAS average for this patient in his 30 days of follow-up was 6 and during this time his morphine rescue requirements decreased up to 70%. Overall there were no adverse effects to treatment although excessive sleepiness was reported by patient 3.
The rationale for choosing a multiple target approach to these complex cases was that we had failed in similar cases before when we just irradiated the hypophysis . Irradiating the thalamus bilaterally might have worked alone but published data at higher doses was not effective in the majority of patients . Also, in our experience, irradiating this area alone is that the effects could be short-lived and be as brief as only one week as seen in non-oncological pain . Thus, a triple target strategy with substantially lower doses seemed to be safe and hopefully a successful clinically approach.
Refractory oncological pain imposes a high burden on patients and caregivers worldwide, the earlier reports of radiosurgery to the hypophysis have shown high grades of quick pain relief practically in all series, nevertheless, the experience is extremely limited, and the numbers are very small as can be appreciated in the scoping review of literature of the last 50 years. From the clinical point of view, this might be the preferred approach for pain derived from extensive metastases to the bone mainly in breast and prostate cancer patients, modern doses with a single target approach have been in the magnitudes of 140-150 Gy and most series do not report clinical adverse endocrine events such as diabetes insipidus. In our initial experience, it was clear that this treatment alternative was highly effective in reducing pain but by no means does it eliminate pain and in most cases, flairs of pain are to be expected especially days or weeks close to the death of the patients . As in all complex pain, a multiple drug-intervention approach is needed, and active surveillance and assistance from pain medication when necessary. Our current understanding of the underlying mechanisms of pain relief when a high dose of radiation is delivered to the hypophysis is merely speculative but the redirection of oxytocin is suspected, thus a possible radio-endocrine-modulatory effect as opposed to a radiomodulatory effect can be obtained by irradiation of a peripheric nerve or a central pain relay center, where no hormones are produced or stored .
For medial thalamus irradiation for oncological pain, the evidence is even more inconclusive, in our initial series, we treated only one terminally ill oncological patient that experienced pain alleviation from an advanced head and neck cancer . This anatomical area has been better studied as a central pain relay center, the main area of irradiation being the PFc and CM are believed to serve a "gate control" function, propagating only salient noxious stimuli and suppressing certain other stimuli. Also, the CM serves as a relay for the paleospinothalamic tract as some of its afferents are to the cingulum and fornix, it is alleged that this mediates and processes the affective component of pain . Although the least amount of dose capable of radiomodulation in humans is unknown, doses as low as 13 Gy have been reported as capable of inducing cessation of epileptic seizures . Animal models show that in the immediate phase after radiosurgery there might be a lesser focal consumption of glucose, in the median term (days) lesser dose (10-40 Gy) produces an excitatory effect, and higher doses of 50-120 Gy produce an inhibitory effect . Thus, we hypothesize that the area of influence between 12 and 20 Gy isodose might also be important for radiomodulation purposes.
As can be seen in the correlation with the coordinates that we used in the Morel atlas, there are also important differences in areas covered by the 45 Gy isodose line but become more relevant in the 20 Gy isodose line when a Dmax of 90 Gy is delivered either by gamma ray (Knife), Infini technology as opposed to Cyberknife, the physical reasons are mainly due to a different size collimator, a different source-axis distance (SAD), and energy levels that favor gamma ray for a stepper dose fall off. When Infini is used the 45 Gy isodose line covers small parts of the PFc, CM, and the medial dorsal parvocellular (MDpc), with regards to the 20 Gy isodose line we can see a much larger involvement of the PFc and CM as well as the MDpc and the medial dorsal magnocellular (MDmc) and the mediodorsal paralaminar (MDpl) portions of the MD nucleus. For Cyberknife and the 45 Gy isodose line, there is much wider coverage of the PFc and CM as well as the MDpc, MDcm, and MDpl. When the 20 Gy isodose line is concerned most of the PFc and CM are covered also the majority of the MD (mediodorsal) nucleus in its three components. We also can expect involvement of the thalamic nucleus in the lateral group such as the ventroposterolateral (VPL) and the ventroposteromedial (VPM) that are considered part of the spinothalamocortical pathway, these are well known primary sensory nuclei that relay directly to the primary sensitive cortex . The MD, especially its medial portion or the MDpc, is influenced by the 45-20 Gy isodose lines with both Gamma and Cyberknife; these portions of the MD, as well as CM, are part of the anterior nuclei limbic group and the sensorimotor/limbic also known as the bridging nuclei that would include the more medial nucleus, the PFc as well as the central and lateral parts of the MD are considered part of the limbic areas of the thalamus and thus serve a direct role in limbic-associated with affective function [21,22].
Although originally thought that doses below 130 Gy were sub necrotic, evidence in animal studies for epileptic models suggests that a high dose of radiation delivered with a gamma knife has shown a decrease of up to 55% of neuronal firing compared to the control animals, and rats receiving <50 Gy had no signs of necrosis [23,24]. Additional information suggests that in gray matter 100 Gy might be sufficient to cause necrosis and as low as 60 Gy in white matter . Another study using a single dose of 40 Gy did not cause apparent necrosis in minipig's brain thus when a Dmax of 90 Gy is delivered less than a 1.5 mm diameter inside the target might receive a dose equal and superior to 80 Gy . A smaller dose (i.e., 20 Gy the area of influence) and a higher dose of 40-80 Gy might slow neuronal transmission at first, while higher dose might impair neuronal activity posteriorly. The RM effect might be due to both phenomena, with an initial almost immediate decrease in neuronal transmission of pain (thus a favorable clinical outcome) and a later (possible) impairment of neuronal activity.
Recently, successful clinical evidence of SBRT irradiation of the celiac plexus for abdominal pain is emerging, dose is 25 Gy to a relatively large target around the abdominal aorta . Their success rates are high which is very promising, nevertheless, it seems to take time and the patients selected were in a favorable ECOG 1 and intermediate levels of pain VAS six, which is most contrasting with the patients we report with abdominal pain. Based on neuroanatomical knowledge of main pain relay centers and scarce clinical evidence such as the one we present; it might be possible that a peripheric (celiac plexus) and bilateral irradiation to the thalamus (central) might provide a faster radiomodulation (RM) effect in patients in more delicate conditions with higher pain levels (7-10) that merit a faster pain response. There is enough evidence to understand that unilateral irradiation of the mesial structures of the thalamus with ablative dose is safe, in our three patients' bilateral irradiation with a mostly suspected sub ablative dose also seemed safe, there was one patient that reported feeling more sleepy than usual, left to neuroanatomy alone this could be the PFc bilateral inhibition as PFc is associated with sleep, change in patterns, and arousal and also the paraventricular nuclei (Pv) as it is linked and interconnected to the hypothalamic suprachiasmatic nucleus considered the pacemaker of the circadian rhythm with sleep and awake regulation [28,29]. As seen in the 20 Gy isodose line and the correlation to the Morel atlas these two areas can be, especially the latter, encompassed by significant radiation, especially with Cyberknife with the current treatment strategy. Nevertheless, under the context of advanced disease progression and medicine side effects and this being a single patient in this small patient case series, the underlying explanation is inconclusive and larger clinical evidence with this approach is necessary.
These initial case reports provide a proof of concept that the use of smaller doses of radiation in a multiple target approach for the management of complex, refractory oncological pain might potentially be useful where all other alternatives have failed. These patients exemplify diverse and complex pain syndromes emerging from different areas of the body where a single target approach might be otherwise ineffective, multiple neuronal circuitry intervention with lesser and hopefully true sub ablative doses could represent an alternative for treatment. There is animal evidence that 60 Gy or less might be “the true” sub ablative dose, further clinical case series might explore even lesser doses than the ones here reported under a multiple target tactic . Although in terminally ill oncological patients we might reach a thin line between effectiveness such as that demonstrated in the classical series of irradiation of the hypophysis with ablative doses and not being effective with lesser doses, however, it seems worthwhile that an effort must be made to understand the minimal effective dose.
Despite advances in interventional pain medicine and drug delivery, there is a substantial number of patients that suffer quite dearly in their end-of-life phase, efforts are needed to find other alternatives that ameliorate their grieving and improve their quality of life.
In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population as expressed in the VAS and morphine rescue consumption. Further studies are needed with larger case series to demonstrate an improvement in quality of life of these patients and their family members in this critical stage in their lives.
The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy was needed as opposed to single target “large” dose approach that has been tried in the past and at least in our experience has proven ineffective in mixed, refractory oncological pain. By no means, in our experience these treatment strategies either single, dual, or triple target irradiation traduce in elimination of pain in most oncological patients, clinical results have allowed an unmanageable intense pain to be more bearable and to respond better to basal pain medication.
There is very little available published evidence regarding the use of radiosurgery for the management of oncological pain, it seems that minute efforts are being made to innovate in pain management. If 'low doses' of focal radiation can effectively reduce pain significantly in a brief timespan, radiosurgery might prove to be the safest noninvasive alternative available in the management of refractory oncological pain at this moment.
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- Zaer H, Glud AN, Schneider BM, et al.: Radionecrosis and cellular changes in small volume stereotactic brain radiosurgery in a porcine model. Sci Rep. 2020, 10:10.1038/s41598-020-72876-w
- Zaer H, Fan W, Orlowski D, et al.: Non-ablative doses of focal ionizing radiation alters function of central neural circuits. Brain Stimul. 2022, 15:586-97. 10.1016/j.brs.2022.04.001
- Hammer L, Hausner D, Ben-Ayun M, et al.: Single-fraction celiac plexus radiosurgery: a preliminary proof-of-concept phase 2 clinical trial. [In Press]. Int J Radiat Oncol Biol Phys. 2022, 10.1016/j.ijrobp.2022.02.038
- Warren S, Capra NF, Yezierski RP: The somatosensory system I: tactile discrimination and position sense. Fundamental Neuroscience for Basic and Clinical Applications. Fifth Edition. Elsevier, Amsterdam, Netherlands; 2013. 243-57.
- Colavito V, Tesoriero C, Wirtu AT, Grassi-Zucconi G, Bentivoglio M: Limbic thalamus and state-dependent behavior: the paraventricular nucleus of the thalamic midline as a node in circadian timing and sleep/wake-regulatory networks. Neurosci Biobehav Rev. 2015, 54:3-17. 10.1016/j.neubiorev.2014.11.021
Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience
Ethics Statement and Conflict of Interest Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. International Cancer Center, Diagnostic Hospital Ethics Committee issued approval N/A. All safety precautions were reviewed and met for adequate patient selection, and radiation protocols were in a lower dose of radiation with what has been described as safe, guaranteeing that the doses at all targets, as well as organs at risk, would be compliant with international standards, previous experience. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
Cite this article as:
Lovo E E, Moreira A, Cruz C, et al. (May 28, 2022) Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience. Cureus 14(5): e25430. doi:10.7759/cureus.25430
Peer review began: May 14, 2022
Peer review concluded: May 22, 2022
Published: May 28, 2022
© Copyright 2022
Lovo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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Popular Mzansi singer and songwriter Kaylow has returned to the scene with a new song titled “In Love.”
Trust Kaylow to make us all feel loved and also fall in love with his beautiful vocals. The Mzansi singer has always given fans good reason to love him. He continues to do this with his latest song, that is immersed in love and affection.
Earlier on, Kaylow released the song “Ngena” as his first single for the year. Last year, a released a few entries including “Promises”, “24 Hours”, and “Intombi”. The songs were well-received. We still cannot shake off his massive hit “The Soul Cafe”.
Kaylow is out now with a new entry which he titles “In Love”. This is perfect for confessing your feelings to the one you love. Do check the song out below to listen to it. Also, add it to a playlist of your choice this weekend.
Kaylow – In Love
File removed on 20th September, 2023. Click for new music

domain: celebrity


text: Cute baby alert! Loved this session with the Zellmer family. It’s amazing how fast time flies by, it feels like yesterday that I was photographing Jessie & Roy’s fall wedding, which you can view here – it’s so great to watch these two with their sweet little girl. Miss Hattie stole the show with her perfect round cheeks and beautiful baby blue eyes. She has such a variety of expressions, and I think would win any adorable baby contest…take a look at some of my favorite images from their session and I think you’ll agree!

domain: photo


Landscaping is an art that makes use of the medium of nature. The landscaper’s palette includes trees, shrubs, flowers, stones and groundcover.
You do not have to be a professional landscaper, and you do not have to have an artistic knack to beautify your outdoor space. Keep these five essential beginner landscaping ideas in mind, and get started making your outdoor area a place in which you want to linger.
1) Consider Your Needs Before Your Wants
First, consider what you need from your outdoor space. If you have children, will you need play sets such as swings, slides or jungle gyms? Are you planning to install a pool, or do you already have one? Do not forget about the family pets, some of whom may spend a good deal of warm-weather days enjoying the outdoors.
Keep in mind who uses the outdoor space and how they use it. Then figure out how to incorporate those things you want from your landscape into your plans.
Other essential needs to consider are the actual amount of space you have. If you live in a planned unit development or condominium, you do not have to give up your dream of improving any outdoor space that belongs to you. Just adapt your plans to the space you have.
Also, consider the kind of weather your home and yard have to put up with throughout the year. For hot climates, drought-tolerant plants and grasses, as well as gravel can make saving water and money an added boost to your new landscape. Or, if you live in a climate where snow and rain are common, you may want to consider adding groundcover in the form of mulch or gravel to various spots in your yard to keep mud from being tracked indoors.
These are just a few pointers to get you started thinking about what you need from a landscape before you delve into what you want from it.
2) Determine Your Budget
You do not have to go all-out and splurge on your landscape. In fact, since you are a beginner you may want to avoid doing this at all. Plants look different when grouped together in your yard or outdoor area and may change more than you thought after a few months as they fill out.
Have a general budget in mind, but try starting out slow for the first time. You can always add new plants and landscaping features to your yard as you get more adept at landscaping. Remember, trying to take an element, like a full-grown tree or pond feature out is not as easy, or as cheap, as you would expect.
3) Variety Is the Spice of Landscaping
Work to have your trees, plants and flower add dimension and visual appeal by arranging them in strategic ways. Add a circle of impatiens around a favorite tree, or have taller grasses planted in front of a row of trees in your yard. Adding smaller plants in front of taller plants creates more dimension.
Color is important as well. Which flowers will you have blooming during the spring Will you need to replant them each year, and do you want to have this flexibility?
The variety of shrubs and trees you have will also be key in attracting various birds or butterflies, which can add even more spice to your outdoor space’s appeal.
Creating borders with the help of small retaining or garden walls is another way to add visual impact to your landscape. You can hide a vegetable garden by segmenting it off with a low stone garden wall, or if you prefer, you can accentuate it using that same type of garden border depending on its placement.
If you are living with a small outdoor space and have a limited area with which to work, you can still create visual dimension and appeal by getting creative, recycled planters to hang in a pleasing arrangement on your garden or patio wall. Anything from old mason jars to watering cans can make for a perfect planter for a landscape arrangement you create and hang right outside your door.
4) Be Patient
Be patient with your beginner landscaping ideas. You want to give your plants a chance to grow or fill out for a season or two, before you commit to them or give up on them.
You may decide you have changed your mind halfway into beginning the installation of a deck around your garden. Whatever the case, start your project off with an intent to give everything time to come together.
5) Be Flexible with Beginner Landscaping Ideas
Trees will look different as they mature and as seasons change, so be flexible as well as patient with your landscape. Continue to learn and experiment. Soon, you will become a proud, advanced beginner landscaper.


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On 12 May, Luxembourg celebrated their annual Diversity Day. This year the date coincided with the Mental Health Awareness Week, so we decided to focus this year’s theme on mental health.
The day kicked off with a webinar hosted by our Managing Director Frederik Raymond Benoit and Nele Segers, HR Business Partner, who announced the interesting activities we had lined up for the day.
We hosted three workshops on the concept of ‘bringing your whole self to the workplace’, where employees were encouraged to complete their ‘Be your whole self profile’. Afterwards, we organised a lunch on the theme of 'flavours of the world' which was a great opportunity to interact and discuss diversity and inclusion (D&I) topics with our colleagues. Finally, to close the day, we hosted a webinar with our guest speaker Thomas Dunning, who shared his own experience on overcoming mental health issues and how he rebuilt himself while staying true to his authentic self. Thomas is a passionate mental health activist, fuelled to break the stigma that surrounds mental illness. Having suffered with mental health himself, diagnosed with Borderline Personality Disorder, Social Anxiety Disorder and PTSD, Thomas is making it his mission to ensure that no one struggling with their mental health feels alone. It was very inspiring to hear his journey!
The cherry on the cake was the announcement of the upcoming visit of Madame Corinne Cahen, Minister for Family Affairs and Integration in Luxembourg, who came to our office on 18 May to discuss our D&I agenda.
Madame Cahen gave a very insightful speech about the engagement of the Luxembourg government on Diversity and Inclusion and she acknowledged the importance of breaking the bias. Frédérik covered all of the actions that have been taken since Luxembourg signed the Diversity Charter last year. Our unconscious bias training programme that all employees completed is now part of our new-starter pack. We've focused on implementing gender diversity across all our people processes such as hiring, talent management, development, promotions, bonuses and salary increases.
Both Frédérik and the Minister highlighted the importance of mental health in the workplace and how being one’s whole self is so much better for your mental health balance. Frédérik reminded everyone in the Luxembourg office about the five employees who are trained mental first aiders and who are available for anyone when needed.
We’re really proud that Madame Cahen chose to visit IQ-EQ for the Diversity Day and that she participated in our celebration activities. We’re also proud of our very diverse workplace. Our Luxembourg employee population has 38 nationalities, out of which 52% are women and 48% are men.
We’re already looking forward to next year's Diversity Day. In the meantime, don’t forget to bring your whole self to the workplace!

domain: psychology


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Low carbon steel shot has a lower hardness than high carbon steel shot. Because of its microstructure it resist impact well until the moment it suddenly scatters and turns into dust. It is often used for flash descaling. Since low carbon steel shot is softer it not possible to crush it into grit, which is therefore not available.
Grain shape : Spherical
Hardness : 40-45 HRC
Microstructure : Bainitic
Density : ≥ 7.5 g/cm³
Bulk density : Approx. 4.4 g/cm³

domain: chemistry


The Central government said on Thursday it is considering a model legislation on regulating real estate in Delhi.
In reply to a written question in the Rajya Sabha, Minister of State for Urban Development Saugata Roy said "the Delhi Real Estate Management (Regulation and Control) Bill" could serve as reference for other states.
The minister, however, ruled out the constitution of a regulator for the real estate sector for the entire country, saying matters pertaining to local governance and land falls in the list of state subjects as per the Constitution.
CWG stadiums will be ready in time: Govt
The government on Thursday said all stadiums to be used for the next year's Commonwealth Games in Delhi would be completed before the due date.
In a written reply in Rajya Sabha, Minister of State for Urban Development Saugata Roy said that the Jawaharlal Nehru stadium and IG stadium would be completed by March 2010 and SPM swimming pool complex by January next year.
Similarly, the MDC National Stadium would be completed by November 2009 and the Dr Karni Singh shooting range by December 2001.


Ferrari is finalizing the development of an extreme version of the Ferrari SF90 Stradale more oriented towards the track. Until recently it was thought that this model could be called the Ferrari SF90 Special Version. It seems, however, that it will be called; SF90 LM, short for ''Le Mans''. It is, therefore, a reference to the fact that Maranello will race at the same time. at Le Mans with the 499P in the premier class of the WEC. Indeed, it is speculated that this model could be presented precisely on the occasion of the 24 Hours of Le Mans which will be held in 2016. in a few days.
The model that is now available; been intercepted on the road during a test session. In the spy photos, the Maranello supercar still appears disguised with films that cover the bodywork in order to hide the details of the design. Despite the camouflage, however, several interesting things can be observed.
From the images it can be seen; note that Ferrari is; intervened a lot on the aerodynamics of the SF90. In particular, the large rear wing stands outwhich appears to be fixed. Even the diffuser & egrave; all new. Up front, it seems that the technicians have revised the shape of the air intakes. The splitter also seems to be smaller. pronounced.
Obviously, Ferrari shouldn't just have limited itself to intervening on the aerodynamics to improve the load available to its supercar. It is possible that Maranello has worked on the weight, to reduce it and on the setup to further improve driveability. of its SF90.
As regards the powertrain, we remind you that the SF90 Stradale has a 4-litre biturbo V8 engine combined with 3 electric motors. Overall, there are 1,000 hp available. It is possible that for the LM version, the entire powertrain could arrive at delivering greater power.
Therefore, all that remains is to wait for the new features. on the launch of this new supercar from Maranello which will probably be launched; made in a limited number of copies.
[Spy photo: CarScoops]
Limited budget? Redmi Note 12 4G, buy it at the best price from eBay at 154 euros.


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It was an all-around great day for the Brewers. The offense was swinging and the pitching was dominant.
The Brewers didn’t take long to get going. Kolten Wong was hit by a pitch to start the game, and Luis Urias walked to put two runners on in the first. After Rowdy Tellez lined into a double play, Pedro Severino homered to give the Brewers the early 2-0 lead. From there, the Brewers tacked on in the third. Wong doubled to lead off the inning, and Urias drove him in for the 3-0 lead. Severino doubled to move Urias to third, but Urias left the game with an injury. Tyrone Taylor brought in pinch-runner Brice Turang on a sacrifice fly for a 4-0 lead. Tellez brought in another run with an RBI single in the fourth for the 5-0 lead.
The sixth inning blew the game wide open. David Dahl led off with a ground-rule double, and Jonathan Davis moved Dahl to third on a groundout. Andruw Monasterio then hit a ball to Rangers shortstop Yonny Hernandez, but Hernandez had a throwing error that allowed Monasterio to reach second and scored Dahl. Turang moved Monasterio up to third witha a single, and then another throwing error from Hernandez let Monasterio scored and moved Turang to third. Brett Sullivan doubled to drive two more runs in, then Garrett Whitley singled. After a pitching change, Corey Ray brought in a run with a lineout to make it a 10-0 game. In the sixth, the Brewers scored five runs (all charged to Rangers pitcher Nick Tropeano), but all were unearned.
A late home run from Weston Wilson in the eighth brought the scoring to a conclusion for the day. It was an 11 run, 11 hit performance by the offense. 10 different players had a hit in the game, with Pedro Severino the only player to record two. Six Brewers also drew a walk.
Meanwhile, the pitching staff was dominant all day. Luis Perdomo pitched two scoreless innings in his Brewers debut. J.C. Mejia worked around a walk with two strikeouts in an inning of work. Connor Sadzeck worked around a hit and struck out two in a scoreless fourth. Trevor Kelley had a strikeout in the fifth, Hobie Harris worked around a walk for a scoreless sixth, and Thomas Jankins had two strikeouts in a scoreless seventh. Lucas Erceg took the eighth and allowed nouthg, and Nash Walters finished the game in the ninth. Walters did get into a bit of trouble allowing two hits, but got Steele Walker to ground into a double play to end the game and preserve the shutout. In total, the Brewers pitching staff allowed three hits and two walks while striking out eight.
One unfortunate note from the game is Luis Urias’ injury. Report is that he strained his left quad. No word on the severity at this point, Craig Counsell said that the team would have more information tomorrow.
The Brewers return home to Maryvale tomorrow for their home opener against the Padres. Freddy Peralta is on the mound for the Brewers, facing off against Chris Paddack to start. First pitch is at 3:10 pm, and it will be on radio and TV.

domain: sports


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WORLD CLASS LEVELS FROM A.M SNiPER AS HE RISES TO THE LUXURY LIFESTYLE WITH RELEASE OF ‘DIABLO'
OFFICIAL PRESS RELEASE
NEWS PROVIDED BY
Ten Letter PR
Continuing his incredible reign that saw him reach some phenomenal heights in 2019, international rapper A.M. SNiPER releases his brand new single ‘DIABLO’. Going in hard with his 2020 debut A.M SNiPER showcases his dexterity with his slick flow. Depicting the rise to the life of luxury ‘DIABLO’ is an example of A.M. SNiPER’s innovative style as he fuses an electronic tinged beat merging it with a Hip Hop sound.
A sovereign of Ayia Napa his prominence and affluence goes beyond the golden shores of Cyprus. Making an impact worldwide he has culminated staggering figures, which regularly hit the six figure mark. To date his singles ‘Yea Yea Yea’ and ‘Run’ have hit over one million streams on Spotify and his 2019 music video releases amount to a combined total of over 7 million views. His dedicated fan base has earned him a loyal following of ¼ million Instagram followers, who keep up to date with all the latest movements and lavish lifestyle of the musician and entrepreneur.
Steeped with incredible craftsmanship, A.M. SNiPER’s musical discography is a cleverly built a body of work that leads him to be the artist and figure we see today. His genre bending style sits on the spectrum of Hip Hop, whilst paying homage to his roots with a tropical twist. His significance in the scene has led him to collaborate and work with some of the biggest names in music such as Chris Brown, Kanye West, Rick Ross, Wiley, Tinie Tempah, Da Beatfreakz and CoolandDre.
His forte as an entrepreneur spans beyond the depths of a musician and he has numerous ventures that demonstrates his flair as a businessman. From owning the VIP luxury WaterWorld waterpark to his central position throughout the Ayia Napa club and entertainment scene, he not only attracts celebrities and fans from across the globe but is also paramount in their ascent to the island in the summer months.
Marking the beginning of what is yet to be another groundbreaking year for A.M. SNiPER, the King of Ayia Napa releases ‘DIABLO’.
Source Ten Letter PR
April 3, 2020 6:53am ET by Ten Letter PR


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Betsey Johnson Lucky Stars Earflap - Don't step foot outside this season without this stellar Betsey Johnson® earflap cap! You'll keep your ears nice and warm while looking criminally cute. Does it get any better?
Knit design with star pattern throughout.
Pom accent at top.
Braided chin straps with pom accents.
Hand wash warm, lay flat to dry.

domain: fashion


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1. There is no “red card” problem; there is a “narrative” problem
Everybody and their border collie has written about red cards in MLS. So I won’t fall in line here; I’m not writing about red cards in MLS.
Instead, let’s talk about bad narrative … as it relates to red cards in MLS! Because bad narrative carried this conversation – and probably carried it down rabbit holes. Card-carrying journalists (I’m raising my hand here) should be committed forever to stomping out bad narrative. With both feet.
The problem is that it’s just so easy to glom onto bad narrative. Bruce Arena got things started Saturday by suggesting the game was being torn asunder with red cards. Seems there’s one every game, he declared! Well, not true; it’s a tick above one in three games so far.
Either way, Arena empowered or encouraged some other voices (players, supporters, media) to weigh in and, pretty soon, everybody accepted as fact that red cards were way up and that MLS players were unable to untangle what did or did not constituted a bad foul.
Well, there are kernels of truth to it – but also a lot of bad information afloat. So let’s drop a bucket of hard data and common sense over this barn fire of toxic narrative.
First, Arena helped light the fire. Now, the guy is an unbelievable MLS manager, habitually ahead of the curve in navigating the league’s tricky player personal corners. But he’s also a famous curmudgeon! If you handed Arena a free burger and fries, I am convinced he’d complain that you didn’t pick up a shake for him, too.
As for the players who say they don’t understand what constitutes a bad foul, well, league leaders have been pretty clear; there were areas of emphasis this year, including cracking down on dissent and reeling in the percent of red card-worthy fouls that escaped attention. It’s on the players to adjust.
Then came the data. Somehow it got reported that red cards were up by a factor of 3x. Only, that’s not true. As these numbers show, it’s up only slightly from last year and not that far above historical averages.
Here’s some context (“context” typically being the enemy of lazy journalism and bad narrative): We have this conversation, early in the season, in a lot of years. It’s almost an annual rite; happens in late March or early April.
Eventually, players and coaches adjust to the particular emphasis of the season and things stabilize.
You know what other conversation we have every year? It’s the one where players aren’t being properly protected. That one is coming, too, and here’s the number to keep in mind: Last year, reviews from PRO assessed that 28 percent of fouls that warranted red were missed.
2. Kaka … yes, please, we’ll have more of that
Kaka’s performance in Orlando City on Sunday evening was nothing short of a master class.
Here’s a good breakdown of the Brazilian attacker’s night. Or, you can let me sum up: he was everywhere, running the attack, providing key passes, assisting here and there on recovering possession and generally being the man Flavio Augusto da Silva and his Lions’ ownership group wanted when they signed him.
He’s the guy who will help fill that swell new stadium next year. Assuming he stays healthy, that is. And that’s the point.
When we talk about these red cards, anybody who is invested in or interested in the game’s growth, you want guys like that on the field. You don’t want them crumbling under bad tackles..
Kaka helps sell tickets. Most of us agree that we want guys like that on the field. It’s a better product when he’s on the field.
The other point is this: Kaka has long had trouble staying healthy and productive over lengthy stretches. So, watching him gracefully run the show underscores importance of due diligence, of making sure the pricey DPs are guys who can (or have a good chance) to play enough meaningful minutes.
Can Kaka do so in 2016? He’s 33, and he missed Orlando’s first three games of 2016. He did get into 28 games last year, which is good enough. For the MLS fans’ enjoyment, let’s hope he keeps it up.
3. Is it discrimination, or just institutional malaise?
About the U.S. women’s soccer team labor dispute: We can talk until the grass fed cows come home about market conditions and how this is complicated by FIFA’s longstanding nitwittedness on the women’s game, etc. Indeed, that stuff is all worthwhile in the discussion.
But the problem for U.S. Soccer in this labor dispute – one that is likely to get worse for the federation before it better – is that it looks bad. Quite bad. Sometimes “look” trumps market conditions.
If they are making fun of you in the Onion, you are probably on the wrong side of things.
U.S. Soccer just got behind the times here; didn’t properly read the playing field, so to speak. Leaders at the Soccer House in Chicago didn’t see the iceberg, dead ahead, of controversy if they didn’t close some of the yawning gaps between men’s and women’s compensation.
Of course, comparing the men’s FIFA World Cup to the women’s version is apples to oranges in terms of sponsor dollars, TV contracts, etc. That stuff does matter.
But a lot of things matter, like the turf issue (where U.S. Soccer looked awful, and did offer official apologies), the outrageous success of the women’s program compared to the U.S. men’s program and, quite importantly, the ongoing conversation in our country on pay inequity between the sexes.
Leaders should have seen the bigger picture and headed this thing off, should have seen a looming PR battle that they were unlikely to win. Was it discrimination? That’s unlikely; U.S. Soccer president Sunil Gulati is highly educated and a progressive thinker.
More likely, it was just institutional malaise from an organization that remains in an extended period of growing pains. Last year was a tough year for U.S. Soccer; 2016 isn’t looking much better at the moment.
4. What an NFL headline means for MLS
NFL Commissioner Roger Goodell made some news Tuesday when was asked about the possibility of adding playoff teams in pro football’s future. In a nutshell, he said it’s likely.
You’re asking, why do we care? This is soccer content, right?
Two things to know … and then you’ll understand why this is quite relevant.
First, just 12 of 32 NFL teams currently qualify for the playoffs. That’s 37.5 percent. As Goodell points out, it’s the smallest of any U.S. professional league, and he says it’s a good thing for the NFL, largely because it makes the regular season contests so important. And yet, he says momentum is moving toward adding post-season entrants.
Now consider that MLS currently has 12 of 20 teams qualifying for the playoffs. Personally, I’d like to see MLS leaders keep the total to 12 as the league grows soon to 24 clubs – and then looks to be a 28-team operation in the not-to-distant future. But I fear the leaders will keep adding playoff teams as well; it’s in the league’s DNA to do so as a high percentage of playoff qualifiers has always been the MLS way.
So, if they are increasing the percentages of playoff teams in NFL … don’t be surprised to see if keep going that way in MLS. Why?
Because there is ample crossover between NFL and MLS owners. Always has been, starting with the Hunt and Kraft families. Then came Stan Kroenke and Paul Allen and quite possible someone from that huge cattle car of Los Angeles FC owners.
Just something interesting for us all to watch.
5. The Little Five
5a. After watching Columbus in person last week, here’s an encouraging word for the denizens of Crew-ville: Do not panic. No, gathering just two points from four games is not a flattering look. But consider that three of those four contests were on the road. (One at the league champs and one at FC Dallas, a team that almost never loses at home.) But Gregg Berhalter still has a good team. Not a great one, not right now, but a good one … one that still passes well, enjoys good spacing, generally makes good choices, etc. Further, Ethan Finlay should have had a goal or two Saturday outside Dallas. Kei Kamara will heat up at some point.
5b. With Columbus, this is a clear case where some bad results happening at the beginning of the year look worse than a bad run somewhere in the middle, exaggerating the effect and perhaps causing to premature panic-button pounding. Best guess: the Crew will clean up a couple of areas and be fine.
5c. If we talk about a ratio of goals-to-important goals, is there anyone who can match versatile FC Dallas attacker Tesho Akindele? The third-year Canadian international has 13 career MLS strikes. That’s reasonable production, but it’s not that many goals. And yet, he has a big (and getting bigger) list of highly meaningful goals. We talked about it a few months ago here. Now add Saturday’s late, dramatic equalizer against Columbus, one that helped preserve FC Dallas’ spiffy home record over the last two-plus years.
5d. Brek Shea just cannot get out of his own way. He’s got something of a history of this, like this 2012 lapse in good sense. The biggest example, of course, was an ill-advised move to Stoke City that, more or less, cost him two years of his career. Last week, more of the same for the Orlando City winger/outside back; he hit an amazing goal … but also did something quite unwise and potentially dangerous. So he won’t travel this week to Philadelphia as his yellow card has been reportedly elevated to a red.
5e. The MLS year already has a budding, breakout star. It’s Joao Plata from Real Salt Lake, someone finally getting a bigger share of deserved recognition. He had bigger names around him previously at Toronto (Danny Koevermans, Dwayne De Rosario, Julian de Guzman, Torsten Frings, etc.), then moved to Utah, a smaller market where it’s harder to gain national notice. All along, injuries sometimes prevented him from building long periods of sustained recognition. Well, only two teams in MLS will go into Week 6 without a loss. RSL is one of them (along with Orlando City) and Plata’s three goals and three assists are big reasons why.


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What are your driving forces? Motivations? Muse?
Introducing and sharing timeless Japanese aesthetics with a global audience. Reinterpreting Zen philosophy to be understood easily and to help incorporate it in everyday life. Combining art and technology to encourage community interaction.
Who are your inspirations?
Artisans, scientists and engineers. I am inspired by people who are committed to making a positive impact in people’s life whether that is in the field of arts or science.
I am inspired by fine details of everyday objects that are used for generations – items people continue to embrace because they are at once practical and beautiful. My travels have taken me around the world, at every destination I investigate that culture’s traditions, rituals, arts, textiles and crafts; I pay close attention to the dominant colours used therein.
There are many artists I admire. To name a few, I love Burning Man artists, David Best’s Temples and Jen Lewin’s interactive installation, Pool.
Why Origami? How did you get here?
It was autumn 2009, I had quit a job at a mental health practice and was looking for a way of combining my skills and background, motherhood and getting back to art and design industry. I started teaching origami to children and adults in Brighton UK. I was demonstrating origami step by step needed to be seen from distance, I naturally made it big, and here Giant Origami was born!
I have been experimenting with Sonobe unit origami since winter 2012. In the beginning, I was just making cubes or icosahedrons for which I found tutorials on Interweb. I found new freedom in creating through combining colours within the constriction of using uniformed units. I got so good at it, I decided to make it more challenging for myself and ‘Giant’ by assembling a few hundreds of units together.
What was your first project with origami?
Origami is something everyone does with family and friends in Japan; it’s a creative play that is deeply rooted in Japanese culture. However I recall, the very first project of origami must have been making paper wonderland, dolls and doll house furnitures with my mum and brother when I was little. At that time in Japan, Sylvanian Families, a line of collectibles based on the concept of dollhouses and anthropomorphic animal figures, were really popular and I created ‘paper friends’ and ‘paper bed and desk’ for the rabbit and squirrel family I treasured.
How do you decide what colors you will use?
I try to make the colour to be ‘felt’ as well as ‘seen’. I would love to brighten up your life, whether that is to evoke a warm feeling of summer, bringing a cool atmosphere of serenity or ignite the burning desire within.
Use of colour is a prominent force of my creativity. I am endlessly inspired by my surroundings; whether that is my immediate environment or inspirations which I collect through my traveling. And of course my childhood memories of Japan where there are four distinctive seasons, each filled with colourful traditional festivals that celebrate beautiful nature and local customs.
How long do you spend on each piece and do you work on them simultaneously?
When I work with Sonobe units, the initial folding stage is the time consuming part. Sometimes I get so bored with the repetitiveness and force myself to JUST DO IT. Fun part begins once plenty of units in variety of colours are folded, then I just let my creativity flow. It’s like playing with LEGO. You can build a shape, deconstruct a part of it or add some more here and there. The process is spontaneous, intuitive and fun, and for me it’s almost meditative.
Do you sketch or plan them out?
I create mood board every now and then to find my new focus, and have a digital photo library that I have built over time that are both my memories as well as inspirations. I treat Sonobe units like LEGO. I have folded thousands of units in different colours over time and nowadays I pick and choose the colour from that stock to create infinite variations of Sonobe unit wall pieces.
What other materials other than paper, have you used?
I love the way paper is easily obtained. It’s so versatile and I don’t need special tools to create something from a sheet of paper however I use plastic sheets when constructing outdoor installation and for my product range. I love food, so I have played with pastries, nori seaweed(sushi), sliced cheese, wraps and dumplings and my friends and family love them! Origami food is something I would love to experiment with more.
When did you decide to do site specific installations?
It was a true ‘Being at the right place at the right time’ moment. One cold winter day on a train from London to Brighton in February 2010, I started chatting to a woman about my giant origami workshops and my wild idea of creating an installation. She LOVED the idea, and happened to be the Creative Director of Secret Garden Party (UK’s alternative to Burning Man Festival). she suggested that I apply for their arts grant and showcase Giant Origami installation at Secret Garden Party .
How was your first installation experience?
When I was awarded with grant from Secret Garden Party to create Giant Origami installation, I was sooooooo ready. The last show before this was my Fine Art graduation show at Central Saint Martins College. After graduating, I worked in photography and print design, then few years devoting my time for my son and working for a mental health practice part-time. After a long hiatus from creative industry I felt like it was the perfect time for me to find my style and create my own mark. Having experience in other areas in my life, I am more focused than ever, and appreciate having the time to concentrate on my art.
When did your interest in art peak? When did you know this was what you wanted to practice?
My love of travel took me to different parts of the world. Everywhere I went I was excited about knowing people were simply fascinated by Japanese culture and at the same time I was frustrated by how Japanese culture was viewed in the stereotypical manner such as traditional images of Geisha and Sumo wrestler, and bright neon signs of Tokyo and Toyota hybrid cars. I simply wanted to act like an ambassador of Japanese culture and art, and inspire people by showing something more rooted in everyday life of Japan. I thought origami was the perfect medium to represent what I was trying to do.
What are you currently working on?
I’m working on radically scaling up Roborigami project. I cannot tell you in details yet but this is going to be super awesome. I now have an app developer and sound artist on board as well as very talented collaborators of four years Ad, the robotics engineer, and Pete, the user interface designer.
In February 2015, I decided to go studio free to live a minimal life. The decision did not come easily since I live in a small apartment with my son, but I realised that Macbook Pro, iPhone, Fuji x100, Moleskine, and colourful paper and small tools are all I need to create and stay connected with people around the world. My simple life shaped up to be minimal expense and more free time and money to actually enjoy life.Nowadays I work from my (tiny) apartment in the city of Brighton UK, I create on a small table that doubles as a dining table. It makes me motivated to finish work before dinner time and tidy up each day. There is an under-bed space where I keep my suitcase filled with paper and small tools. I am really enjoying how simple my setting is. When it’s sunny, my apartment is filled with abundant natural light and I take all my photos by the window.This morning I was working on Sonobe wall piece commission from my apartment. I am currently typing answers for this interview in a converted church cafe in my neighbourhood. When I’m in need of friendly company I take my macbook pro to MakerLab studio where I also teach monthly origami robot workshop.Have you collaborated with another artist?
I had lot of fun folding illustrator/print designer Natasha Coverdale’s print for some of my Giant Origami pieces.
How was Roborigami established?.
After a very successful first year touring festivals and teaching Giant Origami, I was looking for a way of making my installation more playful and fun. It was another ‘Being at the right place at the right time’ moment. Pete and Ad were showcasing their robotised haptic lotus at Secret Garden Party, and they saw my fox installation there too.
Upcoming shows or exhibits?
My current mission is to connect with global audience, so my main focus is my Instagram gallery and interweb features such as this one. Sharing my work via social media and Interweb is amazing. I am here in Brighton UK and I can connect with thousands of people around the world instantaneously.
I will send you a printable gift when you sign up to my fortnightly newsletter and follow me on Instagram. I will keep you updated!
For more on Coco, read this Little Story about her journey.

domain: design


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May 13, 2011
A new version of truthBy Greyhawk
(Or What's the story? Part 4)
From part three:
In today's news:
Today CBS news discovers what we've known all along - important missions are recorded with teensy weensy cameras:
Begging the question: have you seen the footage from the doggy cam?
Of course not. They haven't seen any of it. More accurate statement of CBS policy: No one at CBS or anywhere else outside the US Government has seen the video recorded during the Osama bin Laden raid, however, we're willing to write the phrase "we now know" - followed by the 17th US government version of what happened in the compound that sounds a hellalot better than the first several versions released by the White House - without explaining how we now know anything at all. You will accept that without question.
They've added a video simulation to depict the goings on, to help you better visualize what we now know.
Katie Couric adds an extra element of believability to the whole thing with her question at the end - are you surprised that this super secret stuff has leaked? The right answer is "Katie, nothing has leaked. Until we actually see the video we have no idea whether this new version of the story is true or not. It might be the last one we hear, or we might get a different one tomorrow."
It would be nice to think CBS will replace Couric with someone capable of asking better questions - like "how many more versions of this event that was recorded live from 47 different camera angles do you think we'll get?" - but in reality she, like David Martin, was just reading from a script, one her replacement will follow, too.
Let's jump back to part 2:
What I said on day one about the various conflicting stories might prove to be the last word for the whole thing:All are plausible. But for those and other details, you can pick whichever version you think is likely, but you can't choose which is true.
So let's work with the assumption that this version of the story is true (and for the record, I would very much like it to be true), and that earlier White House versions of the raid with details like "the SEALS killed bin Laden's wife to get to him" and "the SEALs only shot bin Laden's wife in the leg, but we aren't sure she was bin Laden's wife" are not true.
Why are there at least two not true versions of the story from the White House - both released after there was time to debrief the SEAL Team and review the video - at all? "Fog of war" doesn't work as an answer - the op was too small and enough time had passed to eliminate that. (Speaking of which, does the phrase "Officials reviewing those videos are still reconstructing a more accurate version of what happened" in the CBS "news" report give you confidence that you'll eventually get "the real truth"?)
Since the true version is so freaking awesome (and whether it's true or not it is awesome), why wasn't the video of those few seconds (scrubbed of any identifying data and even the actual impacts, if you wanted) released in week one? Why not now?
Version one of the story - the "million dollar mansion with wife as human shield" version in which SEALs killed bin Laden's wife to get at him - came from White House counterterror czar John Brennan. Version two came shortly after: "She "rushed the US assaulter and was shot in the leg, but not killed," White House spokesman Jay Carney told reporters." That also matched elements of the story from survivors from within the compound as relayed by Pakistani officials - but their version includes a claim that bin Laden was captured alive, dragged downstairs, and then executed. It absolutely doesn't matter what you choose to believe in America - but guess which version will be widely believed in certain segments of the Islamic world - especially after the first White House version has proven to be (ahem) "not true." (Real men of genius: today we salute you, Mr White House Counterterrorism Czar...). Bin Laden's wife is apparently very much alive, by the way. This story says she was shot in the leg. Maybe she'll have more to say later...
It's certainly possible she was shot in the leg and shoved aside, but any specific detail isn't what matters here - nor is the point that releasing the video won't stop batshit crazy conspiracy theorists from believing their batshit crazy conspiracy theories. The point is that the White House maintaining a tight grip on "Obama's football" makes every batshit crazy conspiracy theory plausible. And the new best version (best from my point of view) of the story has no source whatsoever. While the CBS story includes vaguely authoritative statements that "Officials reviewing those videos are still reconstructing a more accurate version of what happened..." and "The top Democrat on the House Intelligence Committee went to CIA headquarters Thursday to view photos the SEALs took of bin Laden's body," nowhere in the report do they ever state even a vague source for what CBS claims "we now know." Did CBS make the whole thing up?
Elsewhere: Jimbo notes the innernets meme on whether or not the SEAL cams were fed live to the White House. He's right - it's not a significant issue. (See also my comment from part three, above.) Other concerns aside, the key point is that even if the White House wanted a live feed, they'd be looking at (as Jimbo says) "dozens of blurry, shaky feeds from helmet cams all at once." No matter how well planned and rehearsed, you don't know until you go in whether bin Laden's in the bedroom, kitchen, or wherever - so there's no way to predict which video feed would be "the one."
But there's also no excuse for not having that video (those videos) - along with de-briefs - available to the key folks in D.C. the next morning, at the latest. And there's nothing wrong with "no comment" until you knew what had happened. "Be first with the truth" is an old and painful lesson from this war, one the Obama administration failed completely in this case.
More reactions here.
And CNN says the US has interviewed three bin Laden widows: "The youngest of the three widows, 29-year-old Amal Ahmed Abdulfattah of Yemen, was shot in the leg early on May 2 by a small team of U.S. Navy SEALs." (Can that be true? It wasn't in the CBS video sim...) CNN adds they were "'hostile' toward the Americans, according to a senior Pakistani government official with direct knowledge..." etc.
I want to believe the CBS description of the SEAL's actions are true - but these are the folks who brought us "abu Ghraib" and George Bush's "National Guard records" - the first a half truth (see also here and here and here...) and the second a blatant fabrication. Is "yeah - but they fired Rather and Mapes" a good enough 'reason to believe' now?
Annnnnnd damn I keeping noticing more stuff - like "Leon Panetta, director of the CIA, revealed there was a 25 minute blackout during which the live feed from cameras mounted on the helmets of the US special forces was cut off." Okay - but the mission took 40 minutes (we're told...). So there was 15 minutes of live video feed to the White House? If so, disregard Jimbo's point that there was no live video feed to the White House (and all the good reasons there shouldn't be).
Why the hell is this story - certainly one of the best in recent years - so screwed up?
Posted by Greyhawk / May 13, 2011 9:30 AM | Permalink
Disney seeks SEAL Team 6 trademark - which is indeed pathetic. But they won't be able to cash in on the White House side of the bin Laden kill - Warner Brothers has had "Looney Tunes" trademarked for years, (Which is too bad, because that part really ... Read More
The Associated Press with "new details" of the bin Laden raid (that differ from the CBS TV version of what "we now know"). The AP touts "officials briefed on the operation " who "spoke on condition of anonymity to describe a classified operation..." "A... Read More
November 26, 2010
I think anyone who's ever pondered the "comment" option - once only available on blogs and bulletin boards, now ubiquitous on almost any web site - will appreciate this:
The so-called faculty of writing is not so much a faculty of writing as it is a faculty of thinking. When a man says, "I have an idea but I can't express it"; that man hasn't an idea but merely a vague feeling. If a man has a feeling of that kind, and will sit down for a half an hour and persistently try to put into writing what he feels, the probabilities are at least 90 percent that he will either be able to record it, or else realize that he has no idea at all. In either case, he will do himself a benefit.
That's wisdom from the past, captured for posterity at the US Naval Institute, shared via the web on the institute's 137th anniversary.
From their about page:
"The Naval Institute has three core activities," among them, History and Preservation:
The Naval Institute also has recently introduced Americans at War, a living history of Americans at war in their own words and from their own experiences. These 90-second vignettes convey powerful stories of inspiration, pride, and patriotism.
Take a look at the collection, and you'll see it's not limited to accounts from those who served on ships at sea, members of the other branches are well-represented.
I'm fortunate to have met USNI's Mary Ripley, she's responsible for the institute's oral history program (and she's the daughter of the late John Ripley, whose story is told here). She also deserves much credit for their blog. ("We're not the Navy nor any government agency. Blog and comment freely.") We met at a milblog conference - Mary knew (and I would come to realize) that milbloggers are the 21st-century version of exactly what the US Naval Institute is all about. Once that light bulb came on in my head, I mentioned a vague idea for a project to her - milblogs as the 21st century oral history that they are.
"Put that in writing," she said (of course - see first paragraph above!) - and here's part of the result.
Shortly after the first tent was pitched by the American military in Iraq a wire was connected to a computer therein, and the internet was available to a generation of Americans at war - many of whom had grown up online. From that point on, at any given moment, somewhere in Iraq a Soldier, Sailor, Airman or Marine was at a keyboard sharing the events of his or her day with the folks back home. While most would simply fire off an email, others took advantage of the (then) relatively new online blogging platforms to post their thoughts and experiences for the entire world to see. The milblog was born - and from that moment to this stories detailing everything from the most mundane aspects of camp life to intense combat action (often described within hours of the event) have been available on the web...
And et cetera - but since you're reading this on a milblog, you probably knew that. And you know that milblogs aren't just blogs written by troops at war, that many friends, family members, and supporters likewise documented their story of America at war online in near-real time, as those stories developed.
The diversity in membership of that group is broad, the one thing we all have in common is the impulse to make sense of the seemingly senseless, and communicate the tale - for each of us that impulse was strong enough to overcome whatever barriers prevent the vast majority of people from doing the same. Everyone at some point has some vague idea they believe should be shared - we were the people who, from some combination of internal and external urging, found and spent those many half hours persistently trying to write it down.
But where will all that be in another 137 years? Or five or ten, for that matter. That's something I've asked myself since at least 2004 - when I wrote this:
Membership in the ghost battalion has grown in the years since, and an ever growing majority of those abandoned-but-still-standing sites are vanishing. Have you checked out Lt Smash's site lately? How about Sgt Hook's? If you're a long-time milblog reader you know the first widely-read milblog from Operation Iraq Freedom and the first widely-read milblog from Afghanistan are both gone from the web. If you're a relative newcomer to this world you may never even have heard of them - or the dozens upon dozens of others who carried forth the standard they set down.
If you have a vague notion that something should be done about that, (a notion I've heard expressed more than once...) then you and I and the good folks at the US Naval Institute are in agreement. Preserving the history documented by the milbloggers is just one of the goals of the milblog project, the once-vague idea that we're now making real.
And it's a big idea, if I say so myself - too big to explain in one simple blog post, so stand by for more. Likewise, it's too big a task to be accomplished by just one person. So if you're a milblogger (and exactly what is a milblogger? is a topic for much further discussion on its own) I'm asking for your help. All I'll really need is just a little bit (maybe just one or two of those half hours...) of your time, and your willingness to tell the tale.
We've already made history, it's time to save it.
(More to follow...)
The Mudville Gazette is the on-line voice of an American warrior and his wife who stands by him. They prefer to see peaceful change render force of arms unnecessary. Until that day they stand fast with those who struggle for freedom, strike for reason, and pray for a better tomorrow.
Furthermore, I will occasionally use satire or parody herein. The bottom line: it's my house.
I like having visitors to my house. I hope you are entertained. I fight for your right to free speech, and am thrilled when you exercise said rights here. Comments and e-mails are welcome, but all such communication is to be assumed to be 1)the original work of any who initiate said communication and 2)the property of the Mudville Gazette, with free use granted thereto for publication in electronic or written form. If you do NOT wish to have your message posted, write "CONFIDENTIAL" in the subject line of your email.
Original content copyright © 2003 - 2011 by Greyhawk. Fair, not-for-profit use of said material by others is encouraged, as long as acknowledgement and credit is given, to include the url of the original source post. Other arrangements can be made as needed.
Contact: greyhawk at mudvillegazette dot com


Product Features pump Z6 ZN6
- Sturdy design with casted discharge head and motor support
- Avialable in AISI 304 or AISI 316
- Delivery up to: 78 m3/h
- Head up to: 700 m
- Max immersion depth: 350 m
The Z6-ZN6 Series is designed for use in 6” wells. The head and motor support of this lightweight and sturdy pump is cast in stainless steel as are the shaft sleeves ensuring long lasting reliability and efficiency.
pump Z6 ZN6
The pump has a high sand handling capability which make the Z6-ZN6 series suitable for use in aggressive environments such as water supply from deep wells or irrigation over large areas such as golf courses.
Z6: AISI 304
ZN6: AISI 316
All Z6-ZN6 pumps can be coupled to NEMA standard motors.
Z6 SERIES PUMPS
Among the various products considered there are also some typologies of pumps with the characteristics defined by the specific Regulation (EU) n. 547/2012 implementing the requirements of Directives EuP and ErP.
For vertical multi-stage pumps (MS-V for the Regulations), the efficiency evaluation refers to:
- just the pump and not the pump and motor assembly (electric or combustion);
- pumps with a nominal pressure PN not higher than 25 bar (2500 kPa);
- pumps designed to operate at a speed of 2900 min-1 (for electric pumps this means 50 Hz 2-pole electric motors);
- pumps with a maximum flow of 100 m3 /h;
- use with clean water at a temperature ranging from -10°C to 120°C (the test is performed with cold water at a temperature not higher than 40°C)
SPECIFICATIONS Z6 ZN6
- Delivery: up to 78 m3 /h.
- Head: up to 700 m.
- Maximum overall diameter of pump:
– Standard version: 142 mm (one cable guard included).
– High head version:
177 mm (one cable guard and 6” motor coupling included).
193 mm (one cable guard and 8” motor coupling included).
- Maximum pump immersion depth:
300 m (with L4C motor)
350 m (with L6W and L8W motors).
- Maximum permissible quantity of suspended sand:
- Construction materials available:
AISI304 stainless steel (Z6),
AISI316 stainless steel (ZN6)
APPLICATIONS Pumps Z6 ZN6
- Water supply from deep wells.
- Pressure boosting and water distribution
- Supply of surge tanks and reservoirs.
- Firefighting and washing systems.
- Water table level control.


text:
Chinese exports beat expectations with 9.5pc jump in August
CHINA's exports jumped 9
CHINA's exports jumped 9.5 per cent year on year in August in dollar volume - the biggest increase of any month this year and above expectations of a 7.5 per cent rise, reported London's Financial Times.
The rise in exports underlined China's dominant role in global trade during the coronavirus pandemic and its recovery from it.
Chinese exports have risen year on year for three straight months, raising hopes of a wider resurgence in international trade that has been affected by the outbreak.
'This by itself is a good sign for global trade,' said Louis Kuijs, head of Asia economics at Oxford Economics, adding that the data had 'again surprised on the upside'.

domain: statistics


The 11mm Nagler Type 6 slots in perfectly between the 13mm and 9mm Type 6s and makes a perfect companion to the 7mm.
The 7-element, Nagler Type 6 design is based on the original patented Nagler design. This new 7-element design update for the short focal length Nagler deserves its own designation. Using different exotic materials, coating processes and design ingenuity, Al has massaged more eye-relief, contrast, and true field of view into the shorter focal length Naglers, while maintaining the absolute sharpness of the originals. Eye-relief is 12mm on each model, and all are sized about the same as the original 7mm! Weight about 0.4 to 0.5 lbs.
Why Are There 3 Types of Naglers?
To achieve the full magnification range over 82° apparent field of view requires two types: Nagler Type-5 with focal lengths of 31, 26, 20, 16mm and Nagler Type-6 with focal lengths of 13, 11, 9, 7, 5, 3.5, 2.5mm.
The Type-5 permits the largest true field possible (31mm has 42mm field stop), while the shorter focal length Type-6 models are parfocal, with similiar size and weight and all with a comfortable 12mm eye relief.
The Type-4 models feature about 18mm of eye relief and with the "instajust" eyeguard are best for eyeglass wearers or Dioptrx users in their 22, 17, 12mm focal length range.
|Focal Length (mm)
|Barrel Size (in.)
|Apparent Field of View (deg.)
|Eye Relief (mm)
|Weight (lb / oz)
||0.42 / 6.7
|Field Stop (mm)