Abscopal effect in metastatic breast cancer treated with stereotactic body radiotherapy in the absence of immunotherapy

PurposeIn this study, we aimed to assess the abscopal effect (AE) after CyberKnife stereotactic body radiotherapy (SBRT) in metastatic breast cancer patients without immunotherapy.MethodsWe reviewed breast cancer patients who received SBRT with a fraction size of ≥ 6 Gy for metastatic lesions between July 2008 and December 2021. We selected patients who had at least one measurable extracranial lesion in addition to SBRT target lesions and were not treated with immunotherapy. A total of 40 SBRT cases from 34 patients were included in the analysis. The AE was defined as occurring before the overall progression of the disease, regardless of the use of systemic treatment.ResultsThe median follow-up duration was 16.4 months. Among 40 SBRT cases, the AE was observed in 10 (25.0%) with a median interval of 2.1 months. Of these lesions, 70.0% did not progress for one year. In multivariate logistic regression analysis, no change in systemic treatment after SBRT was significantly associated with an increase in the AE (odds ratio [OR] = 1.428, 95% confidence interval [CI] = 1.108 – 1.841, p = 0.009). A post-SBRT neutrophil-to-lymphocyte ratio (NLR) of < 2 marginally increased the AE (OR = 1.275, 95% CI = 0.998 – 1.629, p = 0.060). However, a high SBRT dose and large planning target volume did not (p = 0.858 and 0.152, respectively) in univariate analysis.ConclusionsOne out of four patients experienced the AE after SBRT in the absence of immunotherapy. The AE could occur more frequently when systemic treatment remains unchanged, and patients have a low NLR after SBRT

Análisis comparativo de los conflictos internos caso de estudios: Somalia(1991-1995) y Siria (2011-2012)

Tesis(Licenciatura en Diplomacia y Relaciones Internacionales)--Universidad Americana, Managua, 2013El presente trabajo monográfico presenta un análisis comparativo sobre los conflictos internos de África y Oriente Próximo, tomando como casos de estudio Somalia y Siria, al realizar dicha comparación entre ambos conflictos ayudará a conocer y comprender que aspectos son similares y cuáles se diferencia entre ambos países

Radiofrequency Neurotomy of Cervical Medial Branches for Chronic Cervicobrachialgia

Chronic neck and arm pain or cervicobrachialgia commonly occurs with the degeneration of cervical spine. Authors investigated the usefulness of radiofrequency (RF) neurotomies of cervical medial branches in patients with cervicobrachialgia and analyzed the factors which can influence the treatment outcome. Demographic data, types of pain distribution, responses of double controlled blocks, electrical stimulation parameters, numbers and levels of neurotomies, and surgical outcomes were evaluated after mean follow-up of 12 months. Pain distribution pattern was not significantly correlated with the results of diagnostic blocks. Average stimulation intensity was 0.45 V, ranging from 0.3 to 0.69, to elicit pain response in cervical medial branches. The most common involvement of nerve branches was C4 (89%), followed by C5 (82%), C6 (75%), and C7 (43%). Among total of 28 patients, nineteen (68%) reported successful outcome according to outcome criteria after 6 months of follow-up (p=0.001), and eight (42%) of 19 patients reported complete relief (100%) of pain. Four patients showed recurrence of pain between 6 and 12 months. It was therefore concluded that cervical medial branch neurotomy is considered useful therapeutic modality for the management of cervicobrachialgia in selected patients, particularly in degenerative zygapophyseal disorders

Modelo de rentabilidade das explorações leiteiras em S. Miguel : influência dos fatores de produção : da classificação morfológica e da produção leiteira dos bovinos

Dissertação de Mestrado em Engenharia Zootécnica.Tendo presente que a situação económica das explorações leiteiras dos Açores está a atravessar grandes dificuldades económicas e financeiras, e com o aproximar do fim anunciado das quotas leiteiras e consequente liberalização total na produção de leite (PL) na Europa, a pecuária açoriana necessita de se preparar para esta nova mudança de estratégia europeia sob o risco de falência da atividade. Dessa forma, pretende-se conhecer a situação técnico-económica e a eficiência técnica das explorações, avaliar o efeito que a produção de leite aos 305 dias (PL305) e a classificação morfológica (CM) terão na rentabilidade líquida (RL), para depois criar um modelo que possa explicar a rentabilidade das explorações. Foram realizadas a análise não paramétrica de eficiência, a análise de variância, a análise cluster e a regressão linear dos registos da PL305, gordura aos 305 dias (PG305), proteína aos 305 dias (PP305) e a CM de 91 explorações que realizaram contraste leiteiro (CL) e foram inscritas em regime de contabilidade organizada no ano de 2010. Constatou-se que as explorações tinham auferindo um RL anual de 1.002,93€/ha, representando um lucro médio de 19,80%. Contudo, cada exploração recebe de subsídios por hectare (Subs/ha) 1.090,06€/ha, o que representa 22,43% do total das receitas e uma clara dependência das explorações aos subsídios (Subs), caso contrário, o lucro médio passaria a -4,20%. Com a certeza do fim anunciado das quotas leiteiras e o corte do Subs aos Produtos Lácteos, prevê-se uma quebra média dos rendimentos em 10,36%. Do lado das despesas, os custos alimentares (CAlim) são os que representam a maior percentagem da despesa com 25,32%. Após a análise não paramétrica de eficiência dos registos verificou-se, que apenas 7,69% das explorações estudadas são eficientes, baixando para os 5,49% quando se retira os Subs/ha atribuídos como forma de rendimento. Na análise de variância observou-se, que não existe qualquer efeito significativo da PL 305 e a Pontuação Final (PF) das explorações na RL das mesmas. Em contrapartida, existe uma forte correlação e um efeito significativo entre a PL305 e a PF (r=0,748, p<0,001) comprovando, que as explorações com as melhores PF são ao mesmo tempo as melhores produtoras de leite. O mesmo se passa na PG305 e na PP305. Na análise de cluster constatou-se, que as explorações mais rentáveis têm um PL305 de 9.188,56 kg, venda de leite (VL) de 5.146,29€, CAlim de 771,65€, Cabeças Normais/ha (CNha) de 3,07e PF de 82,3 pontos. A confirmar estes dados, o modelo criado pela regressão linear múltipla com R2=0,736 estabelece, que de todas as variáveis independentes somente a VL (p<0,001), Calim (p<0,001), Custos com Salários (CSalár, p<0,001), Custos com as Rendas (CRend, p<0,01) e a CNha (p<0,05) são as variáveis com efeito significativo na RL das explorações leiteiras. Assim, os dados revelam que as explorações necessitam de melhorar a qualidade morfológica das vacas leiteiras, de forma a aumentar a PL, proteína e gordura, levando a um aumento da VL, atendendo ao limite máximo dos CAlim e do CNha, de forma a melhorar a eficiência técnica e serem rentáveis sem Subs.ABSTRACT: As we know the dairy farms in Azores are crossing some economical and financial difficulties and with the announced order of milk quotas and complete liberalization of the markets, the farmers in Azores need to be well prepared to face this change in Europe. Because if they don't, they may crash. That is why, it is very important to know the real economical and technical conditions of the farms, as well as the technical efficiency of the farms, and evaluate the effect that the milk production has at 305 days (PL305) and the morphological classification (CM) will have in the net profitability (RL). After that it is important to create a model that can explain the profitability of farms. In order to do that, several things have been made such as: non-parametric analysis of efficiency, analysis of variance, analysis of the cluster, the linear regression of the records of PL305, fat at 305 days (PG305), protein at 305 days (PP305) and the CM of 91 farms that have made their milk recording (CL) and have made their proper accounting in 2010. We found that the farms have earned around 1.002,93€ per hectare, which represented an average profit of 19,80%. However, each farm receives 1.090,06€ per hectare of EU subsidies (Subs/ha), representing 22,43% of the profits and shows a clear dependence on EU subsidies (Subs), because without them, the average profit would be -4.20%. With the end of the milk quotas and the cut in subs for Dairy Products we anticipate an average break in profits around 10.36%.Speaking about the expense, the food costs (CAlim) represent the major percentage of the expense: 25,32%. After the non-parametric analysis of efficiency, we found that only 7,69% of the analyses farms are efficient, decreasing for 5,49%, if we take out the subs/ha. In the analysis of variance we noticed that there isn't any significant effect of the PL305 and the final score (PF) in the RL of the farms. On the other hand, there is a strong relation between the PL 305 and the PF (r=0,748, p<0,001) proving that the farms with the best PF are at the same time the best milk producers. The same happens at PG305 and at PP305. In the cluster analysis we observed that the most profitable farms have a 9.188,56kg of PL305, milk sales (VL) of 5.146,29€, CAlim 771,65€, normal heads /ha (CNha) of 3,07 and PF of 82,3 points. Confirming this facts, the model created by the multiple linear regression with R2=0,736 sets that between all the independent variables only the VL (p<0,001), CAlim (p<0,001), wage costs (CSalár, p<0,001), costs with rents (CRend, p<0,01) and the CNha (p<0,05) are the variables with significant effect in the RL of the farms. Therefore, data shows that the farms need to improve the morphological quality of cows, in order to increase the PL, proteins and fat, taking to an increase of VL, so that they could improve the technical efficiency and be rentable without subs

Induction of Remission is Difficult due to Frequent Relapse during Tapering Steroids in Korean Patients with Polymyalgia Rheumatica

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 ± 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment

Protease Activity Increases in Plasma, Peritoneal Fluid, and Vital Organs after Hemorrhagic Shock in Rats

Hemorrhagic shock (HS) is associated with high mortality. A severe decrease in blood pressure causes the intestine, a major site of digestive enzymes, to become permeable – possibly releasing those enzymes into the circulation and peritoneal space, where they may in turn activate other enzymes, e.g. matrix metalloproteinases (MMPs). If uncontrolled, these enzymes may result in pathophysiologic cleavage of receptors or plasma proteins. Our first objective was to determine, in compartments outside of the intestine (plasma, peritoneal fluid, brain, heart, liver, and lung) protease activities and select protease concentrations after hemorrhagic shock (2 hours ischemia, 2 hours reperfusion). Our second objective was to determine whether inhibition of proteases in the intestinal lumen with a serine protease inhibitor (ANGD), a process that improves survival after shock in rats, reduces the protease activities distant from the intestine. To determine the protease activity, plasma and peritoneal fluid were incubated with small peptide substrates for trypsin-, chymotrypsin-, and elastase-like activities or with casein, a substrate cleaved by multiple proteases. Gelatinase activities were determined by gelatin gel zymography and a specific MMP-9 substrate. Immunoblotting was used to confirm elevated pancreatic trypsin in plasma, peritoneal fluid, and lung and MMP-9 concentrations in all samples after hemorrhagic shock. Caseinolytic, trypsin-, chymotrypsin-, elastase-like, and MMP-9 activities were all significantly (p<0.05) upregulated after hemorrhagic shock regardless of enteral pretreatment with ANGD. Pancreatic trypsin was detected by immunoblot in the plasma, peritoneal space, and lungs after hemorrhagic shock. MMP-9 concentrations and activities were significantly upregulated after hemorrhagic shock in plasma, peritoneal fluid, heart, liver, and lung. These results indicate that protease activities, including that of trypsin, increase in sites distant from the intestine after hemorrhagic shock. Proteases, including pancreatic proteases, may be shock mediators and potential targets for therapy in shock

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

Expression of Bcl-2 and Bax in Mouse Renal Tubules during Kidney Development

Bcl-2 and Bax play an important role in apoptosis regulation, as well as in cell adhesion and migration during kidney morphogenesis, which is structurally and functionally related to mitochondria. In order to elucidate the role of Bcl-2 and Bax during kidney development, it is essential to establish the exact location of their expression in the kidney. The present study localized their expression during kidney development. Kidneys from embryonic (E) 16-, 17-, 18-day-old mouse fetuses, and postnatal (P) 1-, 3-, 5-, 7-, 14-, 21-day-old pups were embedded in Epon. Semi-thin serial sections from two E17 kidneys underwent computer assisted 3D tubule tracing. The tracing was combined with a newly developed immunohistochemical technique, which enables immunohistochemistry on glutaraldehyde fixated plastic embedded sections. Thereby, the microstructure could be described in detail, and the immunochemistry can be performed using exactly the same sections. The study showed that Bcl-2 and Bax were strongly expressed in mature proximal convoluted tubules at all time points, less strongly expressed in proximal straight tubules, and only weakly in immature proximal tubules and distal tubules. No expression was detected in ureteric bud and other earlier developing structures, such as comma bodies, S shaped bodies, glomeruli, etc. Tubules expressing Bcl-2 only were occasionally observed. The present study showed that, during kidney development, Bcl-2 and Bax are expressed differently in the proximal and distal tubules, although these two tubule segments are almost equally equipped with mitochondria. The functional significance of the different expression of Bcl-2 and Bax in proximal and distal tubules is unknown. However, the findings of the present study suggest that the mitochondrial function differs between mature proximal tubules and in the rest of the tubules. The function of Bcl-2 and Bax during tubulogenesis still needs to be investigated

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation