Features of the Physical and Social Neighborhood Environment and Neighborhood-Level Alzheimer's Disease and Related Dementia in South Carolina.

BACKGROUND: Studies are increasingly examining the relationship between the neighborhood environment and cognitive decline; yet, few have investigated associations between multiple neighborhood features and Alzheimer's disease and related dementias (ADRD). OBJECTIVE: We investigated the relationship between neighborhood features and ADRD cumulative incidence from 2010 to 2014 in the South Carolina Alzheimer's Disease Registry (SCADR). METHODS: Diagnosed ADRD cases ≥50 years of age were ascertained from the SCADR by ZIP code and census tract. Neighborhood features from multiple secondary sources included poverty, air pollution [particulate matter with a diameter of 2.5 micrometers or less (PM2.5)], and rurality at the census-tract level and access to healthy food, recreation facilities, and diabetes screening at the county level. In addition to using Poisson generalized linear regression to estimate ADRD incident rate ratios (IRR) with 95% confidence intervals (CIs), we applied integrated nested Laplace approximations and stochastic partial differential equations (INLA-SPDE) to address disparate spatial scales. We estimated associations between neighborhood features and ADRD cumulative incidence. RESULTS: The average annual ADRD cumulative incidence was 690 per 100,000 people per census tract (95% CI: 660, 710). The analysis was limited to 98% of census tracts with a population ≥50 years old (i.e., 1,081 of 1,103). The average percent of families living below the federal poverty line per census tract was 18.8%, and ∼20% of census tracts were considered rural. The average percent of households with limited access to healthy food was 6.4%. In adjusted models, every 5µg/m3) increase of PM2.5 was associated with 65% higher ADRD cumulative incidence (IRR=1.65; 95% CI: 1.30, 2.09), where PM2.5 at or below 12 µg/m3 is considered healthy. Compared to large urban census tracts, rural and small urban tracts had 10% (IRR=1.10; 95% CI: 1.00, 1.23) and 5% (IRR=1.05; 95% CI: 0.96, 1.16) higher ADRD, respectively. For every percent increase of the county population with limited access to healthy food, ADRD was 2% higher (IRR=1.02; 95% CI: 1.01, 1.04). CONCLUSIONS: Neighborhood environment features, such as higher air pollution levels, were associated with higher neighborhood ADRD incidence. The INLA-SPDE method could have broad applicability to data collected across disparate spatial scales. https://doi.org/10.1289/EHP13183.

Health disparities in mortality among individuals with HIV-associated dementia in South Carolina.

HIV disproportionately affects the South compared to other regions of the US. Some people living with HIV (PLWH) may acquire HIV-associated neurocognitive disorders (HAND), of which HIV-associated dementia (HAD) is the most severe form. This study aimed to examine the disparities in mortality among individuals with HAD. Data were obtained from the South Carolina Alzheimer's Disease and Related Dementias Registry from 2010 to 2016 (HAD: n = 505; N = 164,982). Logistic regression and Cox proportional hazards models were used to determine mortality related to HIV-associated dementia and potential sociodemographic differences. Adjusted models controlled for age, gender, race, rurality, and place of diagnosis. Individuals diagnosed in a nursing facility were three times more likely to die with HAD compared to those diagnosed in the community (OR: 3.25; 95% CI: 2.08-5.08). Black populations were more likely to die with HAD compared to White populations (OR: 1.52; 95% CI: 0.953-2.42). Disparities in mortality among patients with HAD were found in place of diagnosis and by race. Future research should determine if mortality among individuals with HAD were as a result of HAD or non-HIV related decline.

Evidence of Electron Heating by Alpha Particles in JET Deuterium-Tritium Plasmas.

The fusion-born alpha particle heating in magnetically confined fusion machines is a high priority subject for studies. The self-heating of thermonuclear fusion plasma by alpha particles was observed in recent deuterium-tritium (D-T) experiments on the joint European torus. This observation was possible by conducting so-called "afterglow" experiments where transient high fusion yield was achieved with neutral beam injection as the only external heating source, and then termination of the heating at peak performance. This allowed the first direct evidence for electron heating of plasmas by fusion-born alphas to be obtained. Interpretive transport modeling of the relevant D-T and reference deuterium discharges is consistent with the alpha particle heating observation.

Neighborhood characteristics and dementia symptomology among community-dwelling older adults with Alzheimer's disease.

Background: Neuropsychiatric symptoms (NPSs) lead to myriad poor health outcomes among individuals with Alzheimer's disease (AD). Prior studies have observed associations between the various aspects of the home environment and NPSs, but macro-level environmental stressors (e.g., neighborhood income) may also disrupt the neuronal microenvironment and exacerbate NPSs. Yet, to our knowledge, no studies have investigated the relationship between the neighborhood environment and NPSs. Methods: Using 2010 data among older adults with AD collected from a sample of the South Carolina Alzheimer's Disease Registry, we estimated cross-sectional associations between neighborhood characteristics and NPSs in the overall population and by race/ethnicity. Neighborhood measures (within a 1/2-mile radius of residence) came from the American Community Survey and Rural Urban Commuting Area Code. We categorized median household income into tertiles: < $30,500, $30,500-40,000, and > $40,000, and rurality as: rural, small urban, and large urban. Residential instability was defined as the percent of residents who moved within the past year. NPSs were defined using the Neuropsychiatric Inventory Questionnaire that included the composite measure of all 12 domains. Adjusting for age, sex/gender, race/ethnicity, and caregiver educational attainment, we used negative binomial regression to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for NPSs by neighborhood characteristics. Results: Among 212 eligible participants, mean age was 82 ± 8.7 years, 72% were women, and 55% non-Hispanic (NH)-Black. Individuals with AD living in < $30,500 vs. > $40,000 income neighborhoods had a 53% (PR = 1.53; 95% CI = 1.06-2.23) higher prevalence of NPSs while individuals living in rural vs. large urban neighborhoods had a 36% lower prevalence of NPSs (PR = 0.64; 95% CI = 0.45-0.90), after adjustment. We did not observe an association between residential instability and NPSs (PR = 0.92; 95% CI = 0.86-1.00); however, our estimates suggested differences by race/ethnicity where NH-White older adults living in residential instable areas had lower NPSs (PR = 0.89; 95% CI = 0.82-0.96) compared to NH-Black older adults (PR = 0.96; 95% CI = 0.86-1.07). Discussion: Across racial/ethnic groups, individuals with AD had more symptomology when living in lower income areas. Pending replication, intervention efforts should consider resource allocation to high-need neighborhoods (e.g., lower income), and studies should investigate underlying mechanisms for this relationship.

Lost alpha Faraday cup foil noise characterization during Joint European Torus plasma post-processing analysis.

Capacitive plasma pickup is a well-known and difficult problem for plasma-facing edge diagnostics. This problem must be addressed to ensure an accurate and robust interpretation of the real signal measurements vs noise. The Faraday cup fast ion loss detector array of the Joint European Torus (JET) is particularly prone to this issue and can be used as a testbed to prototype solutions. The issue of separation and distinction between warranted fast ion signal and electromagnetic plasma noise has traditionally been solved with hardware modifications, but a more versatile post-processing approach is of great interest. This work presents post-processing techniques to characterize the signal noise. While hardware changes and advancements may be limited, the combination with post-processing procedures allows for more rapid and robust analysis of measurements. The characterization of plasma pickup noise is examined for alpha losses in a discharge from JET's tritium campaign. In addition to highlighting the post-processing methodology, the spatial sensitivity of the detector array is also examined, which presents significant advantages for the physical interpretation of fast ion losses.

Fusion product measurements by nuclear diagnostics in the Joint European Torus deuterium-tritium 2 campaign (invited).

A new deuterium-tritium experimental, DTE2, campaign has been conducted at the Joint European Torus (JET) between August 2021 and late December 2021. Motivated by significant enhancements in the past decade at JET, such as the ITER-like wall and enhanced auxiliary heating power, the campaign achieved a new fusion energy world record and performed a broad range of fundamental experiments to inform ITER physics scenarios and operations. New capabilities in the area of fusion product measurements by nuclear diagnostics were available as a result of a decade long enhancement program. These have been tested for the first time in DTE2 and a concise overview is provided here. Confined alpha particle measurements by gamma-ray spectroscopy were successfully demonstrated, albeit with limitations at neutron rates higher than some 1017 n/s. High resolution neutron spectroscopy measurements with the magnetic proton recoil instrument were complemented by novel data from a set of synthetic diamond detectors, which enabled studies of the supra-thermal contributions to the neutron emission. In the area of escaping fast ion diagnostics, a lost fast ion detector and a set of Faraday cups made it possible to determine information on the velocity space and poloidal distribution of the lost alpha particles for the first time. This extensive set of data provides unique information for fundamental physics studies and validation of the numerical models, which are key to inform the physics and scenarios of ITER.

Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study.

OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neighborhood Characteristics and the Mental Health of Caregivers Cohabiting with Care Recipients Diagnosed with Alzheimer's Disease.

While studies have documented the influence of caregiver and care recipient factors on caregiver health, it is important to address the potential impact of neighborhood contexts. This study estimated the cross-sectional associations between neighborhood characteristics and mental health among caregivers cohabiting with Alzheimer's disease care recipients that were experiencing severe or non-severe neuropsychiatric symptoms (NPSs) (e.g., aggression/anxiety). We obtained data collected in 2010 on caregivers and care recipients (n = 212) from a subset of South Carolina's Alzheimer's Disease Registry. Neighborhood measures (within 1 mile of the residence) came from the American Community Survey and the Rural-Urban Commuting Area Code. We categorized the neighborhood median household income into tertiles, namely, "low" (<$31,000), "medium" ($31,000-40,758), and "high" (>$40,758), and rurality as "large urban," "small urban," and "rural." We used negative binomial regression to estimate the prevalence ratios (PRs) and 95% confidence intervals (CIs) for caregiver mental health using neighborhood characteristics. The mean age was 58 ± 10.3 years, 85% were women, and 55% were non-Hispanic Black. Among the caregivers cohabiting with a recipient experiencing severe NPS, higher distress was experienced by caregivers living in low- (PR = 1.61 (95% CI = 1.26-2.04)) and medium- (PR = 1.45 (95% CI = 1.17-1.78)) vs. high-income neighborhoods after an adjustment. These results suggest that neighborhood characteristics may amplify other social stressors experienced by caregivers.

Mentorship and Training to Increase Diversity of Researchers and Practitioners in the Field of Aging and Alzheimer's Disease: A Scoping Review of Program Characteristics.

Objectives: Diversity is needed within the aging and Alzheimer's disease and related dementias (ADRD) research and practice workforce to comprehensively address health inequities faced by underrepresented minority (URM) older adults. We conducted a scoping review of training programs designed to diversify the pool of researchers and practitioners in the field of aging and ADRD. Methods: Online database searches yielded 3976 articles published from 1999 to 2019. Fourteen studies met the inclusion criteria. Results: All programs were from the United States and included URM populations. Nine programs included students, one targeted university faculty, and four targeted clinical staff. Only five programs were guided by theory. Discussion: Our review identified URMs' desire for culturally diverse and representative mentorship, the need for career development support at various training stages, and the importance of incorporating theory to program design. It also identified key characteristics for future program development, creation of systematic evaluation standards, and opportunities for promotion.

Knowledge evaluation instruments for dementia caregiver education programs: A scoping review.

With the increase in our older adult population, there is a need for dementia training for informal and formal dementia caregivers. The objective of this scoping study is to assess dementia knowledge instruments utilized in educational programs and interventions intended for formal and informal dementia caregivers. Scoping review methodology was used to search PubMed, PsycInfo, CINAHL and Web of Science with tailored database search terms. The search yielded 8101 results, with 35 studies meeting inclusion. Studies were conducted in eight countries, had varying study designs (randomized controlled trials [RCTs] = 9, non-RCTs = 6, one-group study design = 20) and utilized previously published (19) and author developed (16) instruments. Furthermore, the studies were internationally diverse, conducted in the United States (n = 18), Australia (n = 7), UK (n = 3), China (n = 2), Canada (n = 2), Taiwan (n = 1), Brazil (n = 1) and multi-country (n = 1). Only two studies focused on minority populations. While author-developed instruments may be more relevant and timesaving, studies should strive to validate instruments or use previously published instruments to help standardize findings across studies and understand better the effects of educational programs on caregiver knowledge. Geriatr Gerontol Int 2020; 20: 397-413.

Weight Status and Sedentary Behavior of Alzheimer's Disease Caregivers.

Objectives: In this study, we sought to characterize the weight status, sedentary behavior, and physical activity of caregivers of individuals with Alzheimer's disease. Methods: In 2014, we surveyed caregivers of individuals with Alzheimer's disease from the South Carolina Alzheimer's Disease Registry (N = 47) about their personal health behaviors. Additionally, a subset of individuals (N = 14) wore an accelerometer for 7 days. Results: Caregivers (N = 47) were mostly overweight or obese (85%) and self-reported a daily average sedentary time of 246.5 ± 203.0 minutes and 455.8 ± 291.4 minutes, as measured by 2 questionnaires. Objective measures indicated that persons spent an average of 769.4 ± 167.6 minutes per day (77.8% of their waking day) engaged in sedentary behavior. Conclusion: Given the negative health outcomes associated with both obesity and sedentary behavior, this is a vulnerable population that likely would benefit from interventions focused on weight management and reducing sedentary behavior.

Upgrades to the in-vessel calibration light source on JET.

Since 2010, an in-vessel calibration light source (ICLS) has been used periodically on JET to calibrate a range of diagnostics at UV, visible, and IR wavelengths. During shutdowns, the ICLS (which is essentially an integrating sphere) is positioned within the vacuum vessel by the remote handling (RH) system. Following the 2013 calibration runs, several changes were made to improve the efficiency and quality of the calibrations. Among these was the replacement of a 20 m "umbilical" cable which carried power and other electrical signals through a vessel port to/from a control cubicle. A lightweight 2 m cable now plugs directly into a single connector on the RH manipulator system, greatly reducing the time required for deployment and improving operational flexibility; e.g., the vessel access "floor" no longer needs to be installed. This change also means the system would be compatible with calibrations after a high neutron-fluence period of operation. An on-board micro-spectrometer now allows for real-time verification of the emitted spectrum. Finally, new "baffles" were designed and installed within the integrating sphere itself, greatly improving the spectral radiance uniformity at non-normal viewing angles (necessary due to orientation uncertainties with the RH system).

Insights into the CuO nanoparticle ecotoxicity with suitable marine model species.

Metal oxide nanoparticles, among them copper oxide nanoparticles (CuO NPs), are widely used in different applications (e.g. batteries, gas sensors, superconductors, plastics and metallic coatings), increasing their potential release in the environment. In aquatic matrix, the behavior of CuO NPs may strongly change, depending on their surface charge and some physical-chemical characteristics of the medium (e.g. ionic strength, salinity, pH and natural organic matter content). Ecotoxicity of CuO NPs to aquatic organisms was mainly studied on freshwater species, few tests being performed on marine biota. The aim of this study was to assess the toxicity of CuO NPs on suitable indicator species, belonging to the ecologically relevant level of consumers. The selected bioassays use reference protocols to identify Effect/Lethal Concentrations (E(L)C), by assessing lethal and sub-lethal endpoints. Mortality tests were performed on rotifer (Brachionus plicatilis), shrimp (Artemia franciscana) and copepod (Tigriopus fulvus). While moult release failure and fertilization rate were studied, as sub-lethal endpoints, on T. fulvus and sea urchin (Paracentrotus lividus), respectively. The size distribution and sedimentation rates of CuO NPs, together with the copper dissolution, were also analyzed in the exposure media. The CuO NP ecotoxicity assessment showed a concentration-dependent response for all species, indicating similar mortality for B. plicatilis (48hLC50 = 16.94 ± 2.68mg/l) and T. fulvus (96hLC50 = 12.35 ± 0.48mg/l), followed by A. franciscana (48hLC50 = 64.55 ± 3.54mg/l). Comparable EC50 values were also obtained for the sub-lethal endpoints in P. lividus (EC50 = 2.28 ± 0.06mg/l) and T. fulvus (EC50 = 2.38 ± 0.20mg/l). Copper salts showed higher toxicity than CuO NPs for all species, with common sensitivity trend as follows: P. lividus ≥ T. fulvus (sublethal endpoint) ≥ B. plicatilis >T. fulvus (lethal endpoint) >A. franciscana. CuO NP micrometric aggregates and high sedimentation rates were observed in the exposure media, with different particle size distributions depending on the medium. The copper dissolution was about 0.16% of the initial concentration, comparable to literature values. The integrated ecotoxicological-physicochemical approach was used to better describe CuO NP toxicity and behavior. In particular, the successful application of ecotoxicological reference protocols allowed to produce reliable L(E)C data useful to identify thresholds and assess potential environmental hazard due to NPs.

The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS.

BACKGROUND: Tachykinins have been implicated in the pathophysiology of IBS with diarrhoea (IBS-D). Our aim was to study the efficacy and safety of ibodutant, a selective neurokinin-2 (NK2) receptor antagonist, in patients with IBS-D. METHODS: This multinational double-blind, placebo-controlled study recruited 559 patients with IBS-D according to Rome III criteria. After a 2-week treatment-free run-in, patients were randomised to ibodutant 1 mg, 3 mg, 10 mg or placebo once daily for eight consecutive weeks. Responders were those with a combined response of satisfactory relief (weekly binary question yes/no) of overall IBS symptoms and abdominal pain/discomfort on ≥75% weeks (primary end point). Secondary end points included abdominal pain and stool pattern. Data were also analysed according to US Food and Drug Administration (FDA)-approved interim end points (improvement of pain and stool consistency). Safety was assessed by monitoring adverse events and laboratory tests. Prespecified statistical analysis involved the whole group as well as gender subgroups. RESULTS: Demographics and baseline characteristics were comparable for all treatment arms. In the overall population, responsiveness tended to increase with escalating ibodutant doses. In the prespecified analysis by gender, ibodutant 10 mg demonstrated significant superiority over placebo in females (p=0.003), while no significant effect occurred in males. This was confirmed for secondary end points and for the responder analysis according to FDA-approved end points. The tolerability and safety of ibodutant was excellent at all doses. CONCLUSIONS: Ibodutant showed dose-dependent efficacy response in IBS-D, reaching statistical significance at the 10 mg dose in female patients. The safety and tolerability profile of ibodutant was similar to placebo. TRIAL REGISTRATION NUMBER: NCT01303224.

Self-propulsion against a moving membrane: Enhanced accumulation and drag force.

Self-propulsion (SP) is a main feature of active particles (AP), such as bacteria or biological micromotors, distinguishing them from passive colloids. A renowned consequence of SP is accumulation at static interfaces, even in the absence of hydrodynamic interactions. Here we address the role of SP in the interaction between AP and a moving semipermeable membrane. In particular, we implement a model of noninteracting AP in a channel crossed by a partially penetrable wall, moving at a constant velocity c. With respect to both the cases of passive colloids with c>0 and AP with c=0, the AP with finite c show enhancement of accumulation in front of the obstacle and experience a largely increased drag force. This effect is understood in terms of an effective potential localised at the interface between particles and membrane, of height proportional to cτ/ξ, where τ is the AP's reorientation time and ξ the width characterizing the surface's smoothness (ξ→0 for hard core obstacles). An approximate analytical scheme is able to reproduce the observed density profiles and the measured drag force, in very good agreement with numerical simulations. The effects discussed here can be exploited for automatic selection and filtering of AP with desired parameters.

Critical phenomena in active matter.

We investigate the effect of self-propulsion on a mean-field order-disorder transition. Starting from a φ^{4} scalar field theory subject to an exponentially correlated noise, we exploit the unified colored-noise approximation to map the nonequilibrium active dynamics onto an effective equilibrium one. This allows us to follow the evolution of the second-order critical point as a function of the noise parameters: the correlation time τ and the noise strength D. Our results suggest that the universality class of the model remains unchanged. We also estimate the effect of Gaussian fluctuations on the mean-field approximation finding an Ornstein-Zernike-like expression for the static structure factor at long wavelengths. Finally, to assess the validity of our predictions, we compare the mean-field theoretical results with numerical simulations of active Lennard-Jones particles in two and three dimensions, finding good qualitative agreement at small τ values.

In-vessel calibration of the imaging diagnostics for the real-time protection of the JET ITER-like wall.

The in situ absolute calibration of the JET real-time protection imaging system has been performed for the first time by means of radiometric light source placed inside the JET vessel and operated by remote handling. High accuracy of the calibration is confirmed by cross-validation of the near infrared (NIR) cameras against each other, with thermal IR cameras, and with the beryllium evaporator, which lead to successful protection of the JET first wall during the last campaign. The operation temperature ranges of NIR protection cameras for the materials used on JET are Be 650-1600 °C, W coating 600-1320 °C, and W 650-1500 °C.

Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy.

PURPOSE: To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity. METHODS AND MATERIALS: 537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis. RESULTS: The mean age was 74 (range 46-91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p < 0.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p < 0.01), the breast volume (p = 0.05), dose inhomogeneities (p < 0.01) and boost volume (p = 0.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p = 0.02), at multivariate analysis. CONCLUSIONS: The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity.

Guidelines on dermatomyositis--excerpt from the interdisciplinary S2k guidelines on myositis syndromes by the German Society of Neurology.

The present guidelines on dermatomyositis (DM) represent an excerpt from the interdisciplinary S2k guidelines on myositis syndromes of the German Society of Neurology (available at www.awmf.org). The cardinal symptom of myositis in DM is symmetrical proximal muscle weakness. Elevated creatine kinase, CRP or ESR as well as electromyography and muscle biopsy also provide important diagnostic clues. Pharyngeal, respiratory, cardiac, and neck muscles may also be affected. Given that approximately 30% of patients also develop interstitial lung disease, pulmonary function tests should be part of the diagnostic workup. Although the cutaneous manifestations in DM are variable, taken together, they represent a characteristic and crucial diagnostic criterion for DM. Approximately 5-20% of individuals exhibit typical skin lesions without any clinically manifest muscle involvement (amyopathic DM). About 30% of adult DM cases are associated with a malignancy. This fact, however, should not delay the treatment of severe myositis. Corticosteroids are the therapy of choice in myositis (1-2 mg/kg). Additional immunosuppressive therapy is frequently required (azathioprine, for children methotrexate). In case of insufficient therapeutic response, the use of intravenous immunoglobulins is justified. The benefit of rituximab has not been conclusively ascertained yet. Acute therapeutic management is usually followed by low-dose maintenance therapy for one to three years. Skin lesions do not always respond sufficiently to myositis therapy. Effective treatment for such cases consists of topical corticosteroids and sometimes also calcineurin inhibitors. Systemic therapies shown to be effective include antimalarial agents (also in combination), methotrexate, and corticosteroids. Intravenous immunoglobulins or rituximab may also be helpful. UV protection is an important prophylactic measure.