Influence of secondary neutrons induced by proton radiotherapy for cancer patients with implantable cardioverter defibrillators

<p>Abstract</p> <p>Background</p> <p>Although proton radiotherapy is a promising new approach for cancer patients, functional interference is a concern for patients with implantable cardioverter defibrillators (ICDs). The purpose of this study was to clarify the influence of secondary neutrons induced by proton radiotherapy on ICDs.</p> <p>Methods</p> <p>The experimental set-up simulated proton radiotherapy for a patient with an ICD. Four new ICDs were placed 0.3 cm laterally and 3 cm distally outside the radiation field in order to evaluate the influence of secondary neutrons. The cumulative in-field radiation dose was 107 Gy over 10 sessions of irradiation with a dose rate of 2 Gy/min and a field size of 10 × 10 cm². After each radiation fraction, interference with the ICD by the therapy was analyzed by an ICD programmer. The dose distributions of secondary neutrons were estimated by Monte-Carlo simulation.</p> <p>Results</p> <p>The frequency of the power-on reset, the most serious soft error where the programmed pacing mode changes temporarily to a safety back-up mode, was 1 per approximately 50 Gy. The total number of soft errors logged in all devices was 29, which was a rate of 1 soft error per approximately 15 Gy. No permanent device malfunctions were detected. The calculated dose of secondary neutrons per 1 Gy proton dose in the phantom was approximately 1.3-8.9 mSv/Gy.</p> <p>Conclusions</p> <p>With the present experimental settings, the probability was approximately 1 power-on reset per 50 Gy, which was below the dose level (60-80 Gy) generally used in proton radiotherapy. Further quantitative analysis in various settings is needed to establish guidelines regarding proton radiotherapy for cancer patients with ICDs.</p

Impaired psychological recovery in the elderly after the Niigata-Chuetsu Earthquake in Japan:a population-based study

BACKGROUND: An earthquake measuring 6.8 on the Richter scale struck the Niigata-Chuetsu region of Japan at 5.56 P.M. on the 23rd of October, 2004. The earthquake was followed by sustained occurrence of numerous aftershocks, which delayed reconstruction of community lifelines. Even one year after the earthquake, 9,160 people were living in temporary housing. Such a devastating earthquake and life after the earthquake in an unfamiliar environment should cause psychological distress, especially among the elderly. METHODS: Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12) in 2,083 subjects (69% response rate) who were living in transient housing five months after the earthquake. GHQ-12 was scored using the original method, Likert scoring and corrected method. The subjects were asked to assess their psychological status before the earthquake, their psychological status at the most stressful time after the earthquake and their psychological status at five months after the earthquake. Exploratory and confirmatory factor analysis was used to reveal the factor structure of GHQ12. Multiple regression analysis was performed to analyze the relationship between various background factors and GHQ-12 score and its subscale. RESULTS: GHQ-12 scores were significantly elevated at the most stressful time and they were significantly high even at five months after the earthquake. Factor analysis revealed that a model consisting of two factors (social dysfunction and dysphoria) using corrected GHQ scoring showed a high level of goodness-of-fit. Multiple regression analysis revealed that age of subjects affected GHQ-12 scores. GHQ-12 score as well as its factor 'social dysfunction' scale were increased with increasing age of subjects at five months after the earthquake. CONCLUSION: Impaired psychological recovery was observed even at five months after the Niigata-Chuetsu Earthquake in the elderly. The elderly were more affected by matters relating to coping with daily problems

Factor structure of the General Health Questionnaire (GHQ-12) in subjects who had suffered from the 2004 Niigata-Chuetsu Earthquake in Japan: a community-based study

<p>Abstract</p> <p>Background</p> <p>Factor structure of the 12-item General Health Questionnaire (GHQ-12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan.</p> <p>Methods</p> <p>Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores.</p> <p>Results</p> <p>Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score.</p> <p>Conclusion</p> <p>The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.</p

Unique CRF01_AE Gag CTL Epitopes Associated with Lower HIV-Viral Load and Delayed Disease Progression in a Cohort of HIV-Infected Thais

Cytotoxic T Lymphocytes (CTLs) play a central role in controlling HIV-replication. Although numerous CTL epitopes have been described, most are in subtype B or C infection. Little is known about CTL responses in CRF01_AE infection. Gag CTL responses were investigated in a cohort of 137 treatment-naïve HIV-1 infected Thai patients with high CD4+ T cell counts, using gIFN Enzyme-Linked Immunospot (ELISpot) assays with 15-mer overlapping peptides (OLPs) derived from locally dominant CRF01_AE Gag sequences. 44 OLPs were recognized in 112 (81.8%) individuals. Both the breadth and magnitude of the CTL response, particularly against the p24 region, positively correlated with CD4+ T cell count and inversely correlated with HIV viral load. The breadth of OLP response was also associated with slower progression to antiretroviral therapy initiation. Statistical analysis and single peptide ELISpot assay identified at least 17 significant associations between reactive OLP and HLA in 12 OLP regions; 6 OLP-HLA associations (35.3%) were not compatible with previously reported CTL epitopes, suggesting that these contained new CTL Gag epitopes. A substantial proportion of CTL epitopes in CRF01_AE infection differ from subtype B or C. However, the pattern of protective CTL responses is similar; Gag CTL responses, particularly against p24, control viral replication and slow clinical progression

Differential, Phosphorylation Dependent Trafficking of AQP2 in LLC-PK1 Cells

The kidney maintains water homeostasis by modulating aquaporin 2 (AQP2) on the plasma membrane of collecting duct principal cells in response to vasopressin (VP). VP mediated phosphorylation of AQP2 at serine 256 is critical for this effect. However, the role of phosphorylation of other serine residues in the AQP2 C-terminus is less well understood. Here, we examined the effect of phosphorylation of S256, S261 and S269 on AQP2 trafficking and association with recycling pathway markers. We used LLC-PK1 cells expressing AQP2(S-D) or (S-A) phospho mutants and a 20°C cold block, which allows endocytosis to continue, but prevents protein exit from the trans Golgi network (TGN), inducing formation of a perinuclear AQP2 patch. AQP2-S256D persists on the plasma membrane during cold block, while wild type AQP2, AQP2-S256A, S261A, S269A and S269D are internalized and accumulate in the patch. Development of this patch, a measure of AQP2 internalization, was most rapid with AQP2-S256A, and slowest with S261A and S269D. AQP2-S269D exhibited a biphasic internalization profile with a significant amount not internalized until 150 minutes of cold block. After rewarming to 37°C, wt AQP2, AQP2-S261A and AQP2-S269D rapidly redistributed throughout the cytoplasm within 20 minutes, whereas AQP2-S256A dissipated more slowly. Colocalization of AQP2 mutants with several key vesicular markers including clathrin, HSP70/HSC70, EEA, GM130 and Rab11 revealed no major differences. Overall, our data provide evidence supporting the role of S256 and S269 in the maintenance of AQP2 at the cell surface and reveal the dynamics of internalization and recycling of differentially phosphorylated AQP2 in cell culture

Role of ER Stress in Ventricular Contractile Dysfunction in Type 2 Diabetes

BACKGROUND: Diabetes mellitus (DM) is associated with an increased risk of ischemic heart disease and of adverse outcomes following myocardial infarction (MI). Here we assessed the role of endoplasmic reticulum (ER) stress in ventricular dysfunction and outcomes after MI in type 2 DM (T2DM). METHODOLOGY AND PRINCIPAL FINDINGS: In hearts of OLETF, a rat model of T2DM, at 25∼30 weeks of age, GRP78 and GRP94, markers of ER stress, were increased and sarcoplasmic reticulum calcium ATPase (SERCA)2a protein was reduced by 35% compared with those in LETO, a non-diabetic control. SERCA2a mRNA levels were similar, but SERCA2a protein was more ubiquitinated in OLETF than in LETO. Left ventricular (LV) end-diastolic elastance (Eed) was higher in OLETF than in LETO (53.9±5.2 vs. 20.2±5.6 mmHg/µl), whereas LV end-systolic elastance and positive inotropic responses to β-adrenergic stimulation were similar in OLETF and LETO. 4-Phenylbutyric acid (4-PBA), an ER stress modulator, suppressed both GRP up-regulation and SERCA2a ubiquitination and normalized SERCA2a protein level and Eed in OLETF. Sodium tauroursodeoxycholic acid, a structurally different ER stress modulator, also restored SERCA2a protein level in OLETF. Though LV dysfunction was modest, mortality within 48 h after coronary occlusion was markedly higher in OLETF than in LETO (61.3% vs. 7.7%). Telemetric recording showed that rapid progression of heart failure was responsible for the high mortality rate in OLETF. ER stress modulators failed to reduce the mortality rate after MI in OLETF. CONCLUSIONS: ER stress reduces SERCA2a protein via its augmented ubiquitination and degradation, leading to LV diastolic dysfunction in T2DM. Even at a stage without systolic LV dysfunction, susceptibility to lethal heart failure after infarction is markedly increased, which cannot be explained by ER stress or change in myocardial response to sympathetic nerve activation

Social Participation and Disaster Risk Reduction Behaviors in Tsunami Prone Areas

This paper examines the relationships between social participation and disaster risk reduction actions. A survey of 557 households in tsunami prone areas in Phang Nga, Thailand was conducted following the 2012 Indian Ocean earthquakes. We use a multivariate probit model to jointly estimate the likelihood of undertaking three responses to earthquake and tsunami hazards (namely, (1) following disaster-related news closely, (2) preparing emergency kits and/or having a family emergency plan, and (3) having an intention to migrate) and community participation.We find that those who experienced losses from the 2004 tsunami are more likely to participate in community activities and respond to earthquake hazards. Compared to men, women are more likely to prepare emergency kits and/or have an emergency plan and have a greater intention to migrate. Living in a community with a higher proportion of women with tertiary education increases the probability of engaging in community activities and carrying out disaster risk reduction measures. Individuals who participate in village-based activities are 5.2% more likely to undertake all three risk reduction actions compared to those not engaging in community activities. This implies that encouraging participation in community activities can have positive externalities in disaster mitigation

Tradable Pollution Permits and the Regulatory Game

This paper analyzes polluters\u27 incentives to move from a traditional command and control (CAC) environmental regulatory regime to a tradable permits (TPP) regime. Existing work in environmental economics does not model how firms contest and bargain over actual regulatory implementation in CAC regimes, and therefore fail to compare TPP regimes with any CAC regime that is actually observed. This paper models CAC environmental regulation as a bargaining game over pollution entitlements. Using a reduced form model of the regulatory contest, it shows that CAC regulatory bargaining likely generates a regulatory status quo under which firms with the highest compliance costs bargain for the smallest pollution reductions, or even no reduction at all. As for a tradable permits regime, it is shown that all firms are better off under such a regime than they would be under an idealized CAC regime that set and enforced a uniform pollution standard, but permit sellers (low compliance cost firms) may actually be better off under a TPP regime with relaxed aggregate pollution levels. Most importantly, because high cost firms (or facilities) are the most weakly regulated in the equilibrium under negotiated or bargained CAC regimes, they may be net losers in a proposed move to a TPP regime. When equilibrium costs under a TPP regime are compared with equilibrium costs under a status quo CAC regime, several otherwise paradoxical aspects of firm attitudes toward TPP type reforms can be explained. In particular, the otherwise paradoxical pattern of allowances awarded under Phase II of the 1990 Clean Air Act\u27s acid rain program, a pattern tending to favor (in Phase II) cleaner, newer generating units, is explained by the fact that under the status quo regime, a kind of bargained CAC, it was the newer cleaner units that were regulated, and which therefore had higher marginal control costs than did the largely unregulated older, plants. As a normative matter, the analysis here implies that the proper baseline for evaluating TPP regimes such as those contained in the Bush Administration\u27s recent Clear Skies initiative is not idealized, but nonexistent CAC regulatory outcomes, but rather the outcomes that have resulted from the bargaining game set up by CAC laws and regulations

First Direct Observation of Collider Neutrinos with FASER at the LHC

We report the first direct observation of neutrino interactions at a particle collider experiment. Neutrino candidate events are identified in a 13.6 TeV center-of-mass energy $pp$ collision data set of 35.4 fb${}^{-1}$ using the active electronic components of the FASER detector at the Large Hadron Collider. The candidates are required to have a track propagating through the entire length of the FASER detector and be consistent with a muon neutrino charged-current interaction. We infer $153^{+12}_{-13}$ neutrino interactions with a significance of 16 standard deviations above the background-only hypothesis. These events are consistent with the characteristics expected from neutrino interactions in terms of secondary particle production and spatial distribution, and they imply the observation of both neutrinos and anti-neutrinos with an incident neutrino energy of significantly above 200 GeV.Comment: Submitted to PRL on March 24 202