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Zusammenfassung Hintergrund Mit einer Prävalenz von ca. 10 % ist Diabetes mellitus eine der häufigsten chronischen Erkrankungen in Deutschland. Diese geht einher mit erhöhten Raten an depressiven Störungen, Angststörungen und Anpassungsstörungen, die einen besonderen psychotherapeutischen Versorgungsbedarf begründen. Ziel der Arbeit Ziel der Studie ist es, in einer Psychotherapieinanspruchnahmepopulation den Anteil von Patienten mit Diabetes mellitus zu bestimmen und die Charakteristika der Versorgung auch im Vergleich zu Inanspruchnahmepatienten ohne chronische körperliche Erkrankung zu beschreiben. Material und Methoden Ausgehend von einer bevölkerungsrepräsentativen Screeningstichprobe von n = 32.573 wurde im Rahmen des Projektes „Evaluation der Strukturreform der Richtlinien-Psychotherapie – Vergleich von komplex und nicht-komplex erkrankten Patienten“ (ES-RiP) eine Befragung von n = 1544 Patienten, die eine ambulante Psychotherapie in Anspruch genommen haben, durchgeführt. Outcomes waren Inanspruchnahme, Zuweisungswege, Beschwerden und Beschwerdeverlauf, Lebensqualität, Zufriedenheit mit der Behandlung und unerwünschte Nebenwirkungen. Ergebnisse In einer Psychotherapieinanspruchnahmepopulation wiesen in der Selbstangabe 6,7 % (n = 104) einen Diabetes mellitus auf. Gedrückte/schwankende Stimmung, Angststörungen und Probleme im Umgang mit körperlichen Erkrankungen werden von den Inanspruchnahmepatienten mit Diabetes mellitus im Vergleich zu Inanspruchnahmepatienten ohne chronische körperliche Erkrankung signifikant häufiger als zur Therapie motivierende Beschwerden genannt. Bei einer sehr hohen Zufriedenheit mit der Behandlung werden von 81,7 % deutliche Verbesserungen der Beschwerden und von 79,0 % eine Zunahme der Lebensqualität benannt. Über unerwünschte Nebenwirkungen der Psychotherapie berichten 45,7 % der diabeteserkrankten Patienten. Diskussion Der Anteil an Patienten mit Diabetes mellitus in einer Inanspruchnahmepopulation liegt unter der aufgrund von epidemiologischen Daten erwartbaren Prävalenz. In die psychotherapeutische Versorgung führen diese Patienten eine Vielzahl von Belastungen. Das Versorgungssystem sollte durch spezifische Angebote auf diese Patientengruppe eingehen.

Nine new genera, 17 new species, nine new combinations, seven epitypes, three lectotypes, one neotype, and 14 interesting new host and / or geographical records are introduced in this study. New genera: Neobarrmaelia (based on Neobarrmaelia hyphaenes), Neobryochiton (based on Neobryochiton narthecii), Neocamarographium (based on Neocamarographium carpini), Nothocladosporium (based on Nothocladosporium syzygii), Nothopseudocercospora (based on Nothopseudocercospora dictamni), Paracamarographium (based on Paracamarographium koreanum), Pseudohormonema (based on Pseudohormonema sordidus), Quasiphoma (based on Quasiphoma hyphaenes), Rapidomyces (based on Rapidomyces narthecii). New species: Ascocorticium sorbicola (on leaves of Sorbus aucuparia, Belgium), Dactylaria retrophylli (on leaves of Retrophyllum rospigliosii, Colombia), Dactylellina miltoniae (on twigs of Miltonia clowesii, Colombia), Exophiala eucalyptigena (on dead leaves of Eucalyptus viminalis subsp. viminalis supporting Idolothrips spectrum, Australia), Idriellomyces syzygii (on leaves of Syzygium chordatum, South Africa), Microcera lichenicola (on Parmelia sulcata, Netherlands), Neobarrmaelia hyphaenes (on leaves of Hyphaene sp., South Africa), Neobryochiton narthecii (on dead leaves of Narthecium ossifragum, Netherlands), Niesslia pseudoexilis (on dead leaf of Quercus petraea, Serbia), Nothocladosporium syzygii (on leaves of Syzygium chordatum, South Africa), Nothotrimmatostroma corymbiae (on leaves of Corymbia henryi, South Africa), Phaeosphaeria hyphaenes (on leaves of Hyphaene sp., South Africa), Pseudohormonema sordidus (on a from human pacemaker, USA), Quasiphoma hyphaenes (on leaves of Hyphaene sp., South Africa), Rapidomyces narthecii (on dead leaves of Narthecium ossifragum, Netherlands), Reticulascus parahennebertii (on dead culm of Juncus inflexus, Netherlands), Scytalidium philadelphianum (from compressed air in a factory, USA). New combinations: Neobarrmaelia serenoae, Nothopseudocercospora dictamni, Dothiora viticola, Floricola sulcata, Neocamarographium carpini, Paracamarographium koreanum, Rhexocercosporidium bellocense, Russula lilacina. Epitypes: Elsinoe corni (on leaves of Cornus florida, USA), Leptopeltis litigiosa (on dead leaf fronds of Pteridium aquilinum, Netherlands), Nothopseudocercospora dictamni (on living leaves of Dictamnus albus, Russia), Ramularia arvensis (on leaves of Potentilla reptans, Netherlands), Rhexocercosporidium bellocense (on leaves of Verbascum sp., Germany), Rhopographus filicinus (on dead leaf fronds of Pteridium aquilinum, Netherlands), Septoria robiniae (on leaves of Robinia pseudoacacia, Belgium). Lectotypes: Leptopeltis litigiosa (on Pteridium aquilinum, France), Rhopographus filicinus (on dead leaf fronds of Pteridium aquilinum, Netherlands), Septoria robiniae (on leaves of Robinia pseudoacacia, Belgium). Neotype: Camarographium stephensii (on dead leaf fronds of Pteridium aquilinum, Netherlands).

Objectives This retrospective cohort study investigates outcomes of patients with intermediate-high and high-risk pulmonary embolism (PE) who were treated with transfemoral mechanical thrombectomy (MT) using the large-bore Inari FlowTriever aspiration catheter system. Material and Methods Twenty-seven patients (mean age 56.1 ± 15.3 years) treated with MT for PE between 04/2021 and 11/2021 were reviewed. Risk stratification was performed according to European Society of Cardiology (ESC) guidelines. Clinical and hemodynamic characteristics before and after the procedure were compared with the paired Student’s t test, and duration of hospital stay was analyzed with the Kaplan–Meier estimator. Procedure-related adverse advents were assessed. Results Of 27 patients treated, 18 were classified as high risk. Mean right-to-left ventricular ratio on baseline CT was 1.7 ± 0.6. After MT, a statistically significant reduction in mean pulmonary artery pressures from 35.9 ± 9.6 to 26.1 ± 9.0 mmHg (p = 0.002) and heart rates from 109.4 ± 22.5 to 82.8 ± 13.8 beats per minute (p Conclusion In this small study population of predominantly high-risk PE patients, large-bore MT without adjunctive thrombolysis was feasible with an acceptable procedure-related complication rate.

A 65-year-old man experienced sudden onset of abdominal pain while working on his farm without significant trauma. He heard a ‘pop’ sound, followed by abdominal pain, lightheadedness and diaphoresis. He has a history of polycythemia vera (PV) and chronic severe splenomegaly, treated with

Background: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. Methods: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. Results: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P P =0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P =0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P =0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. Conclusions: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

A 43-year-old previously healthy man with hypertension presented to his primary care provider with fevers and dyspnea, after a history of cough and sinus congestion lasting several weeks. A chest radiograph demonstrated prominent interstitial markings with scattered alveolar opacities. Based on the

In central Europe, including Germany, Telekia speciosa (heart-leaved oxeye) is a synanthropic, non-native plant species commonly grown as an ornamental plant. A powdery mildew has recently been introduced on this host in Germany. This powdery mildew has previously been assigned to Golovinomyces cichoracearum (≡ Erysiphe cichoracearum) sensu lato. Two German specimens of powdery mildew on Telekia have been sequenced and phylogenetically analysed. The analyses revealed that the German sequences obtained from the Telekia powdery mildew are identical with a sequence retrieved from Golovinomyces inulae on Pentanema salicinum (≡ Inula salicina) collected in Switzerland. Furthermore, holotype material of G. inulae, described from Korea, has been sequenced, which confirmed G. inulae as causative agent of the Telekia powdery mildew. The current distribution of G. inulae in Germany is briefly discussed including a first report of this pathogen from Austria.

BackgroundThe complete response rate of cervical high-grade squamous intraepithelial lesion (cHSIL) patients to imiquimod immunotherapy is approximately 60%. Consequently, many patients are exposed to unnecessary adverse effects of imiquimod. On the other hand, conventional surgical large loop excision therapy is associated with increased risk of premature births in subsequent pregnancies. An in-depth analysis of the cHSIL immune microenvironment was performed in order to identify and develop a predictive biomarker for response to imiquimod, to maximize therapy efficacy and to avoid adverse effects in patients unlikely to respond.MethodsBiopsies of 35 cHSIL patients, before and 10 weeks on imiquimod treatment, were analyzed by two multispectral seven-color immunofluorescence panels for T cell and myeloid cell composition in relation to treatment response. Based on these results a simplified immunohistochemical detection protocol was developed. Samples were scanned with the Vectra multispectral imaging system and cells were automatically identified using machine learning.ResultsThe immune microenvironment of complete responders (CR) is characterized by a strong and coordinated infiltration by T helper cells (activated PD1+/type 1 Tbet+), M1-like macrophages (CD68+CD163-) and dendritic cells (CD11c+) prior to imiquimod. The lesions of non-responders (NRs) displayed a high infiltration by CD3+FOXP3+regulatory T cells. At 10 weeks on imiquimod, a strong influx of intraepithelial and stromal CD4+T cells was observed in CR but not NR patients. A steep decrease in macrophages occurred both in CR and NR patients, leveling the pre-existing differences in myeloid cell composition between the two groups. Based on the pre-existing immune composition differences, the sum of intraepithelial CD4 T cell, macrophage and dendritic cell counts was used to develop a quantitative simplified one color immunohistochemical biomarker, the CHSIL immune biomarker for imiquimod (CIBI), which can be automatically and unbiasedly quantified and has an excellent predictive capacity (receiver operating characteristic area under the curve 0.95, pConclusionThe capacity of cHSIL patients to respond to imiquimod is associated with a pre-existing coordinated local immune process, fostering an imiquimod-mediated increase in local T cell infiltration. The CIBI immunohistochemical biomarker has strong potential to select cHSIL patients with a high likelihood to experience a complete response to imiquimod immunotherapy.

Purpose Rural residents have a higher cancer burden than urban residents, which is likely related to multiple socioecological factors. This study sought to investigate the perspectives of a diverse set of rural stakeholders regarding access to cancer prevention and control resources in rural southern Illinois. Methods Stakeholders were recruited from counties in southern Illinois and included residents (cancer survivors or caregivers), leaders of community-based organizations with health-related missions, and health care providers. Individual interviews and focus groups assessed recommended cancer prevention, control, and treatment resources; helpfulness of regional resources; and needed resources. The research team used an iterative approach to thematic analysis wherein codes were derived inductively and refined repeatedly to reveal overarching themes. Findings Forty-four stakeholders reported challenges to health care access (eg, travel distance, financial burdens, and poor quality of care) and limited access to supportive care services (lack of caregiver support and "spotty" area resources). To mitigate these barriers, local residents used a combination of individual (self-reliance and adaptive measures) and organizational (patient navigation and financial services) approaches. Finally, stakeholders reported multiple forms of cancer control and prevention communication, including formal discussions with health care providers and various types of informal social support (eg, friends and family). Conclusions Stakeholders experienced barriers to cancer prevention and control often mitigated by a reliance on personal adaptations, nonclinical organizational supports, and informal support systems. While resources remain minimal in southern Illinois, researchers and practitioners must make efforts to leverage existing community organizations and social networks to improve cancer outcomes in this region.

Since the appearance of the E-Cigarette in the early 2000s, its industry, popularity, and prevalence have risen dramatically. In the past, E-Cigarette use with the vaping of nicotine or cannabis products had been associated with a few reported cases of lung injury. However, in 2019, thousands of cases of E-Cigarette or vaping product use-associated lung injury (EVALI) were reported in the United States. Evidence linked this outbreak with vaping of tetrahydrocannabinol (THC). We report two confirmed cases of EVALI and their associated clinical, radiologic, and pathologic features. This report supports the growing body of information regarding EVALI. It also discusses various substances, particularly vitamin E acetate, which has been suggested as a causative agent.

Research has suggested that international students’ transition to the United States is often correlated with less physical activity after arriving in the U.S). One reason might be related to reduced social support when living in a foreign environment. The purpose of this cross-sectional study was to assess the impact of social support on international college students’ physical activity behaviors. Participants (N = 318) from five public universities in one Midwest state completed an electronic survey assessing self-reported physical activity behaviors and perceived social support for exercise (SSE). Data analyses included multiple linear regression, multinomial logistic regression, and multiple logistic regression to test the study’s hypotheses. Region of origin, academic level, and friends’ SSE were all significant predictors of unhealthy physical activity behaviors. Specifically, friends’ SSE was positively associated with higher total physical activity behaviors (F (12, 305) = 4.2, p < .001, R(2) = .142) and was a significant predictor of participants’ physical activity levels. Although research suggests international students’ transition to the United States can impart negative impacts on their physical activity behaviors, we found that greater levels of friends’ SSE was associated with increased physical activity behaviors. As university administrators and wellness programs explore interventions promoting positive physical activity behaviors among international students, they should consider including elements that focus specifically on friendship social support to motivate physical activity behaviors.

Les galopeurs sont capables de courir à plus de 60 km/h sur des distances allant de 900 à 4 000 m pour les courses de plat et de 2 800 à 7 300 m pour les courses d’obstacles. Afin de réaliser de tels efforts, l’approvisionnement en énergie recourt à différentes voies métaboliques dont la contribution dépend de l’intensité et de la durée de l’effort. Une étude de terrain, incluant 11 galopeurs Pur-sang, a été réalisée afin d’évaluer l’implication du métabolisme lipidique lors d’une séance d’entraînement et de déterminer quels marqueurs seraient potentiellement utiles au suivi de l’entraînement. Les analyses biochimiques classiques confirment l’implication du métabolisme lipidique dans l’apport énergétique lors de l’exercice chez le galopeur. Cependant, les informations relatives à leur métabolisation restent limitées. Le recours à de nouveaux marqueurs, tel que le profil en acylcarnitines, apparaît comme un outil intéressant pour investiguer le métabolisme énergétique. Outre l’acquisition de nouvelles connaissances relatives à l’implication des différentes voies métaboliques au cours de l’effort, la détermination du profil des acylcarnitines pourrait s’avérer utile au suivi médicosportif du galopeur.

The mass of the W boson, a mediator of the weak force between elementary particles, is tightly constrained by the symmetries of the standard model of particle physics. The Higgs boson was the last missing component of the model. After observation of the Higgs boson, a measurement of the W boson mass provides a stringent test of the model. We measure the W boson mass, MW, using data corresponding to 8.8 inverse femtobarns of integrated luminosity collected in proton-antiproton collisions at a 1.96 tera-electron volt center-of-mass energy with the CDF II detector at the Fermilab Tevatron collider. A sample of approximately 4 million W boson candidates is used to obtain MW ¼ 80;433:5 T 6:4stat T 6:9syst ¼ 80;433:5 T 9:4 MeV=c2, the precision of which exceeds that of all previous measurements combined (stat, statistical uncertainty; syst, systematic uncertainty; MeV, mega-electron volts; c, speed of light in a vacuum). This measurement is in significant tension with the standard model expectation. © 2022 American Association for the Advancement of Science. All rights reserved.

Individuals with gambling disorder (GD) experience a host of negative psychosocial and physical health outcomes, yet few seek treatment. Of particular concern are individuals with co-occurring mental and behavioral health disorders, a group at higher risk for GD in the state of Ohio. To better serve this population, the Ohio Department of Mental Health and Addiction Services developed a group-based GD treatment manual for adults with co-occurring disorders. Over the course of 5 years, 353 individuals engaged in at least some of the manual’s 12 weekly modules, and more than one-third (n = 122) completed the entire curriculum. Participants who completed all 12 modules completed pre-and post-tests, and after controlling for covariates, participants significantly decreased their GD symptom severity, though changes in self-esteem and gambling urges were non-significant. These findings suggest the treatment manual holds promise at reducing gambling behaviors for individuals with co-occurring disorders, but further research is warranted to explore best practices on how to intervene on the psychological antecedents to gambling in this population.

Purpose Finite proton range affords improved dose conformality of radiation therapy when patient regions-of-interest geometries are well characterized. Substantial changes in patient anatomy necessitate re-planning (RP) to maintain effective, safe treatment. Regularly planned verification scanning (VS) is performed to ensure consistent treatment quality. Substantial resources, however, are required to conduct an effective proton plan verification program, which includes but is not limited to, additional computed tomography (CT) scanner time and dedicated personnel: radiation therapists, medical physicists, physicians, and medical dosimetrists. Materials and Methods Verification scans (VSs) and re-plans (RPs) of 711 patients treated with proton therapy between June 2015 and June 2018 were studied. All treatment RP was performed with the intent to maintain original plan integrity and coverage. The treatments were classified by anatomic site: brain, craniospinal, bone, spine, head and neck (H&N), lung or chest, breast, prostate, rectum, anus, pelvis, esophagus, liver, abdomen, and extremity. Within each group, the dates of initial simulation scan, number of VSs, number of fractions completed at the time of VS, and the frequency of RP were collected. Data were analyzed in terms of rate of RP and individual likelihood of RP. Results A total of 2196 VSs and 201 RPs were performed across all treatment sites. H&N and lung or chest disease sites represented the largest proportion of plan modifications in terms of rate of re-plan (RoR: 54% and 58%, respectively) and individual likelihood of RP on a per patient basis (likelihood of RP [RP%]: 46% and 39%, respectively). These sites required RP beyond 4 weeks of treatment, suggesting continued benefit for frequent, periodic VS. Disease sites in the lower pelvis demonstrated a low yield for RP per VS (0.01-0.02), suggesting that decreasing VS frequency, particularly late in treatment, may be reasonable. Conclusions A large degree of variation in RoR and individual RP% was observed between anatomic treatment sites. The present retrospective analysis provides data to help develop anatomic site–based VS protocols.

Pseudolipomas are an uncommon clinical manifestation appearing as a non-encapsulated prominence of subcutaneous fat on MRI. Post-traumatic pseudolipomas (PTLs) are thought to arise from neoadipogenesis following acute or chronic trauma. These are most commonly located on the lower extremities, gluteal, and trochanteric regions. Here, we report a case of PTL in a high school athlete, arising in the posterior neck after weight training with performing barbell squats without neck padding. To our knowledge, this case represents a novel association between PTLs and weight training exercises.

Introduction/Background* CD103-positive tissue resident memory-like CD8+ T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). We investigated whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration. Methodology We applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Result(s)* Infiltration denisty of CD8CD103 TRM was independent of clinicopathological factors and primary treatment strategy. A survival benefit of CD8CD103 TRM infiltration was observed in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery (high epithelial CD8CD103 TRM infiltration 5 year survival 83% versus 52%, p=0.03; high stromal CD8CD103 TRM 5 year survival 77% versus 54%, p=0.01). No effect of CD8CD103 TRM infiltration on overall survival was observed in patients treated with neo-adjuvant chemotherapy, with or without macroscopic tumor lesions after surgery (high epithelial CD8CD103 TRM infiltration, p=0.77; high stromal CD8CD103 TRM infiltration, p=0.32). Conclusion* Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification, and supports the further exploration of image-based quantification of CD8CD103 TRM in HGSOC. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future.

Objectives The authors examined the associations between work engagement, job satisfaction, and turnover intentions among family medicine residency (FMR) managers. Methods We conducted a cross-sectional online survey of 511 FMR manager members of the Association of Family Medicine Administration using purposive sampling. The Utrecht Work Engagement Scale, Job Satisfaction Survey, and Boshoff and Allen’s 3-item scale were used to assess work engagement, job satisfaction, and turnover intentions respectively. Descriptive statistics, Chi-Square tests, Pearson’s correlations, 2-way contingency table analysis, and hierarchical regression analyses were used to analyze the data. Results The response rate was 70.6% (389/551). Work engagement was positively correlated with job satisfaction (r[387]=.513, p

TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia. To study the role of Trem2 in a mouse model of β-amyloidosis, we compared PS2APP transgenic mice versus PS2APP mice lacking Trem2 (PS2APP;Trem2ko) at ages ranging from 4 to 22 months. Microgliosis was impaired in PS2APP;Trem2ko mice, with Trem2-deficient microglia showing compromised expression of proliferation/Wnt-related genes and marked accumulation of ApoE., TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia. To study the role of Trem2 in a mouse model of β-amyloidosis, we compared PS2APP transgenic mice versus PS2APP mice lacking Trem2 (PS2APP;Trem2ko) at ages ranging from 4 to 22 months. Microgliosis was impaired in PS2APP;Trem2ko mice, with Trem2-deficient microglia showing compromised expression of proliferation/Wnt-related genes and marked accumulation of ApoE. Plaque abundance was elevated in PS2APP;Trem2ko females at 6–7 months; but by 12 or 19–22 months of age, it was notably diminished in female and male PS2APP;Trem2ko mice, respectively. Across all ages, plaque morphology was more diffuse in PS2APP;Trem2ko brains, and the Aβ42:Aβ40 ratio was elevated. The amount of soluble, fibrillar Aβ oligomers also increased in PS2APP;Trem2ko hippocampi. Associated with these changes, axonal dystrophy was exacerbated from 6 to 7 months onward in PS2APP;Trem2ko mice, notwithstanding the reduced plaque load at later ages. PS2APP;Trem2ko mice also exhibited more dendritic spine loss around plaque and more neurofilament light chain in CSF. Thus, aggravated neuritic dystrophy is a more consistent outcome of Trem2 deficiency than amyloid plaque load, suggesting that the microglial packing of Aβ into dense plaque is an important neuroprotective activity. SIGNIFICANCE STATEMENT Genetic studies indicate that TREM2 gene mutations confer increased Alzheimer's disease (AD) risk. We studied the effects of Trem2 deletion in the PS2APP mouse AD model, in which overproduction of Aβ peptide leads to amyloid plaque formation and associated neuritic dystrophy. Interestingly, neuritic dystrophies were intensified in the brains of Trem2-deficient mice, despite these mice displaying reduced plaque accumulation at later ages (12–22 months). Microglial clustering around plaques was impaired, plaques were more diffuse, and the Aβ42:Aβ40 ratio and amount of soluble, fibrillar Aβ oligomers were elevated in Trem2-deficient brains. These results suggest that the Trem2-dependent compaction of Aβ into dense plaques is a protective microglial activity, limiting the exposure of neurons to toxic Aβ species.

The worldwide increase in societal challenges is putting pressure on humanitarian organizations to develop sophisticated approaches to leverage social innovations in the humanitarian sector. Since humanitarian problems are complex problems, with the relevant knowledge being hidden, organizational search theory advocates the application of bottom‐up and theory‐guided search processes to identify the social innovations that solve these. Unfortunately, there has been no theoretical attention to understanding which approaches apply in this context. Further, established theory‐guided bottom‐up search processes, such as the lead user method, are unsuitable to the humanitarian sector, and we lack practice examples of adequate search processes. To start addressing this gap in theory and practice, procedural action research was done with the International Federation of Red Cross and Red Crescent Societies to develop a theory‐guided bottom‐up innovation search process for the real‐life humanitarian problem of recurring floods in Indonesia. It revealed that an innovation search process for this context must differ significantly concerning its objectives and the steps to be taken from the lead user method, which was used as a starting point. Further, a comparison of the technical quality and the social impacts of the identified social innovations with social innovations identified through a non‐theory‐guided bottom‐up search process (i.e., an innovation contest) suggests the superiority of this theory‐guided search process. With this conclusion and the insights derived throughout the development of the search process, this study makes important contributions to theory development in the social and open innovation literatures and delivers important recommendations for social innovation practice in the humanitarian sector.

Purpose To quantify the effects of combining layer‐based repainting and respiratory gating as a strategy to mitigate the dosimetric degradation caused by the interplay effect between a moving target and dynamic spot‐scanning proton delivery. Methods An analytic routine modeled three‐dimensional dose distributions of pencil‐beam proton plans delivered to a moving target. Spot positions and weights were established for a single field to deliver 100 cGy to a static, 15‐cm deep, 3‐cm radius spherical clinical target volume with a 1‐cm isotropic internal target volume expansion. The interplay effect was studied by modeling proton delivery from a clinical synchrotron‐based spot scanning system and respiratory target motion, patterned from surrogate patient breathing traces. Motion both parallel and orthogonal to the beam scanning direction was investigated. Repainting was modeled using a layer‐based technique. For each of 13 patient breathing traces, the dose from 20 distinct delivery schemes (combinations of four gate window amplitudes and five repainting techniques) was computed. Delivery strategies were inter‐compared based on target coverage, dose homogeneity, high dose spillage, and delivery time. Results Notable degradation and variability in plan quality were observed for ungated delivery. Decreasing the gate window reduced this variability and improved plan quality at the expense of longer delivery times. Dose deviations were substantially greater for motion orthogonal to the scan direction when compared with parallel motion. Repainting coupled with gating was effective at partially restoring dosimetric coverage at only a fraction of the delivery time increase associated with very small gate windows alone. Trends for orthogonal motion were similar, but more complicated, due to the increased severity of the interplay. Conclusions Layer‐based repainting helps suppress the interplay effect from intra‐gate motion, with only a modest penalty in delivery time. The magnitude of the improvement in target coverage is strongly influenced by individual patient breathing patterns and the tumor motion trajectory.

IntroductionSince the implementation of human papillomavirus (HPV)-based screening for cervical cancer, the majority of cervical intra-epithelial neoplasia grade 2 (CIN2) lesions are high-risk (hr)HPV positive. Evidence on prognostic factors in hrHPV-positive CIN2 is lacking, hampering the individual counseling of women undergoing observation as routine management. The aim of this study is to identify prognostic factors for the spontaneous regression of hrHPV-positive CIN2.MethodsA retrospective cohort study was conducted at the Maastricht University Medical Center, the Netherlands. Women with hrHPV-positive CIN2 who underwent observation between January 1, 2000 and April 30, 2013 were included. Regression was defined as Pap 1/2 cytology (normal or atypical squamous cells of undetermined significance (ASCUS) cytology) or ≤CIN1 histology at the 24 month follow-up and no diagnosis of ≥CIN2 before the 24 month follow-up visit. Potential prognostic factors (HPV-16/18, p16 staining, KI67 staining, age, smoking status, last Pap smear result, multiple CIN2 lesions, oral contraception use, and parity) were assessed using logistic regression analysis.ResultsA total of 56 women were included in the study, of which 34 (61%) showed spontaneous regression of their lesion. Of all studied potential prognostic factors, only not smoking and nulliparity were significantly associated with disease regression (OR 3.84, 95% CI 1.04 to 14.21, and OR 5.00, 95% CI 1.32 to 19.00, respectively, in the univariate analysis). Both effects remained significant after correction for age and HPV-16/18 in a multivariable regression analysis. In women who smoked, disease regression occurred in 10 of 22 women (46%), compared with 16 of 21 women (76%) who did not smoke. In parous women, regression occurred in 12 of 27 women (44%), compared with 16 of 20 nulliparous women (80%).DiscussionSmoking status and parity may influence the likelihood of disease regression in hrHPV-positive CIN2. These factors could be considered in individual patient counseling regarding the choice between immediate treatment or conservative management.

Purpose The aim of this work is to describe the clinical implementation of respiratory‐gated spot‐scanning proton therapy (SSPT) for the treatment of thoracic and abdominal moving targets. The experience of our institution is summarized, from initial acceptance and commissioning tests to the development of standard clinical operating procedures for simulation, motion assessment, motion mitigation, treatment planning, and gated SSPT treatment delivery. Materials and methods A custom respiratory gating interface incorporating the Real‐Time Position Management System (RPM, Varian Medical Systems, Inc., Palo Alto, CA, USA) was developed in‐house for our synchrotron‐based delivery system. To assess gating performance, a motion phantom and radiochromic films were used to compare gated vs nongated delivery. Site‐specific treatment planning protocols and conservative motion cutoffs were developed, allowing for free‐breathing (FB), breath‐holding (BH), or phase‐gating (Ph‐G). Room usage efficiency of BH and Ph‐G treatments was retrospectively evaluated using beam delivery data retrieved from our record and verify system and DICOM files from patient‐specific quality assurance (QA) procedures. Results More than 70 patients were treated using active motion management between the launch of our motion mitigation program in October 2015 and the end date of data collection of this study in January 2018. During acceptance procedures, we found that overall system latency is clinically‐suitable for Ph‐G. Regarding room usage efficiency, the average number of energy layers delivered per minute was

A 29-year-old male presented with a seven-year history of a slow-growing, painless, firm, mobile mass in the right upper back that was bothersome when supine or with direct pressure. On initial presentation, a clinical diagnosis of lipoma was given. The mass progressively increased in size over several years but remained painless. The mass measured 15 x 10 cm on examination. Excision of the lesion was performed, which revealed a white cut surface with cystic degenerative changes. Histologically, the lesion revealed spindle cell morphology with occasional mitosis. Diffuse immunohistochemical staining with MUC4 supports a diagnosis of low-grade fibromyxoid sarcoma (LGFMS). Tumor was present with focal extension into the deep margin. However, serial magnetic resonance imaging studies performed suggest no residual disease and negative regional lymph node involvement. This case demonstrates the growth pattern of LGFMS, but also denotes the importance of correlating radiological and pathological features to accurately diagnose and treat these tumors in a timely fashion.

ObjectivesMobile health tools have potential to improve the diagnosis and management of acute lower respiratory illnesses (ALRI), a leading cause of paediatric mortality worldwide. The objectives were to evaluate health workers’ perceptions of acceptability, usability and feasibility of Acute Lower Respiratory Illness Treatment and Evaluation (ALRITE), a novel mobile health tool to help frontline health workers diagnose, treat and provide education about ALRI in children DesignA qualitative study including semistructured interviews with health facility administrators and focus groups with primary care health workers.SettingTwo federally funded Ugandan primary care health facilities, one peri-urban and one rural.ParticipantsWe enrolled 3 health administrators and 28 health workers (clinical officers and nurses).InterventionThe ALRITE smartphone application was developed to help frontline health workers adhere to ALRI guidelines and differentiate wheezing illnesses from pneumonia in children under 5 years of age. ALRITE contains a simple decision tree, a partially automated respiratory rate counter, educational videos and an adapted respiratory assessment score to determine bronchodilator responsiveness. We performed a demonstration of ALRITE for participants at the beginning of interviews and focus groups. No participant had used ALRITE prior.ResultsThemes impacting the potential implementation of ALRITE were organised using individual-level, clinic-level and health-system level determinants. Individual-level determinants were acceptability and perceived benefit, usability, provider needs and provider–patient relationship. Clinic-level determinants were limited resources and integration within the health centre. Systems-level determinants included medication shortages and stakeholder engagement.ConclusionsIncorporation of these themes will ready ALRITE for field testing. Early engagement of end users provides insights critical to the development of tailored mHealth decision support tools.

Numerous national guidelines now include primary human papillomavirus (HPV) testing as a recommended screening option for cervical cancer in the United States yet little is known regarding screening intentions for this specific screening strategy or interventions that may increase uptake. Gain- and loss-framed messaging can positively impact health behaviors; however, there is mixed evidence on which is more effective for cervical cancer screening, with no published evidence examining HPV testing. To help address this gap, this study compared the effects of message framing on screening knowledge and intentions related to primary HPV testing. We randomized females aged 21–65 (n=365) to receive brief messaging about cervical cancer screening with either gain- or loss-framing. In January-February 2020, participants completed pretest and posttest measures evaluating cervical cancer knowledge, beliefs, and intentions to be screened using HPV testing. We used generalized estimating equations to model message and framing effects on screening outcomes, controlling for age, education, race, and baseline measures. In comparison to pretest, messaging significantly increased HPV-related screening intentions [aOR: 2.4 (1., 3.5)] and knowledge [aOR: 1.7 (1.2, 2.4)], perceived effectiveness of HPV testing [aOR: 4.3 (2.8, 6.5)], and preference for primary HPV screening [aOR: 3.2 (1.2, 8.5), regardless of message framing. For all outcomes, no significant interaction by message framing was observed. Brief public health messaging positively impacted HPV-related screening intentions, knowledge, and beliefs, independent of message framing. In conjunction with other strategies, these results suggest that messaging could be an effective tool to increase uptake of primary HPV testing.

This study describes the development of a colorectal cancer (CRC) screening multilevel intervention with four primary care clinics in rural Appalachian Kentucky. We also discuss barriers experienced by the clinics during COVID-19 and how clinic limitations and needs informed project modifications. Four primary care clinics were recruited, key informant interviews with clinic providers were conducted, electronic health record (EHR) capacity to collect data related to CRC screening and follow-up was assessed, and a series of meetings were held with clinic champions to discuss implementation of strategies to impact clinic CRC screening rates. Analysis of interviews revealed multilevel barriers to CRC screening. Patient-level barriers included fatalism, competing priorities, and financial and literacy concerns. The main provider- and clinic-level barriers were provider preference for colonoscopy over stool-based testing and EHR tracking concerns. Clinics selected strategies to address barriers, but the onset of COVID-19 necessitated modifications to these strategies. Due to COVID-19, changes in clinic staffing and workflow occurred, including provider furloughs, a state-mandated pause in elective procedures, and an increase in telehealth. Clinics adapted screening strategies to match changing needs, including shifting from paper to digital educational tools and using telehealth to increase annual wellness visits for screening promotion. While significant delays persist for scheduling colonoscopies, clinics were encouraged to promote stool-based tests as a primary screening modality for average-risk patients.

CD103-positive tissue resident memory-like CD8+ T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future.

At the Fermilab Tevatron proton-antiproton (pp¯) collider, high-mass electron-neutrino (eν) pairs are produced predominantly in the process pp¯→W(→eν)+X. The asymmetry of the electron and positron yield as a function of their pseudorapidity constrain the slope of the ratio of the u- to d-quark parton distributions versus the fraction of the proton momentum carried by the quarks. This paper reports on the measurement of the electron-charge asymmetry using the full data set recorded by the Collider Detector at Fermilab in 2001-2011 and corresponding to 9.1 fb-1 of integrated luminosity. The measurement significantly improves the precision of the Tevatron constraints on the parton-distribution functions of the proton. Numerical tables of the measurement are provided. © 2021 authors. Published by the American Physical Society.

The purpose of this study was to assess the extant literature on the relationship between alcohol and sexual assault among college students. A literature search was conducted using the following databases: PubMed, Education Resources Information Center (ERIC), PsycINFO, JSTOR, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Key search terms included sexual assault, alcohol, and college students. A total of 23 articles met inclusion criteria, the plurality (47.8%) of which were cross-sectional and featured convenience samples (43.5%). All studies were conducted at public higher education institutions in the United States. The most salient crosscutting themes included perceived low risk for sexual assault among female college students, higher likelihood of severe sexual assault among women who consumed more alcohol, and general information about polysubstance use and sexual assault risk. Methodological shortcomings included an overreliance on convenience sampling, lack of reporting of where samples were obtained, and single-site data collection. Given the large number of studies that found women who consume alcohol are more likely than their nondrinking counterparts to experience sexual assault, public health educators must continue to prioritize female college students who drink. However, interventions should target potential perpetrators rather than focusing solely on how victims can avoid risky situations. Future research should include diverse, random samples across multiple institutions topromote greater generalizability of findings.

Background: Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Methods: Twenty-five animals received scanned proton beam irradiation. ECG-gated computed tomography scans were acquired at end-expiration breath hold. Structures (atrioventricular junction or left ventricular myocardium) and organs at risk were contoured. Doses of 30, 40, and 55 Gy were delivered during expiration to the atrioventricular junction (n=5) and left ventricular myocardium (n=20) of intact animals. Results: In this study, procedural success was tracked by pacemaker interrogation in the atrioventricular junction group, time-course magnetic resonance imaging in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 Gy caused slowing and interruption of cardiac impulse propagation at the atrioventricular junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks. Conclusions: Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.

Background Colorectal cancer (CRC) screening rates are lower in Appalachian regions of the United States than in non-Appalachian regions. Given the availability of various screening modalities, there is critical need for culturally relevant interventions addressing multiple socioecological levels to reduce the regional CRC burden. In this report, we describe the development and baseline findings from year 1 of “Accelerating Colorectal Cancer Screening through Implementation Science (ACCSIS) in Appalachia,” a 5-year, National Cancer Institute Cancer MoonshotSM-funded multilevel intervention (MLI) project to increase screening in Appalachian Kentucky and Ohio primary care clinics. Methods Project development was theory-driven and included the establishment of both an external Scientific Advisory Board and a Community Advisory Board to provide guidance in conducting formative activities in two Appalachian counties: one in Kentucky and one in Ohio. Activities included identifying and describing the study communities and primary care clinics, selecting appropriate evidence-based interventions (EBIs), and conducting a pilot test of MLI strategies addressing patient, provider, clinic, and community needs. Results Key informant interviews identified multiple barriers to CRC screening, including fear of screening, test results, and financial concerns (patient level); lack of time and competing priorities (provider level); lack of reminder or tracking systems and staff burden (clinic level); and cultural issues, societal norms, and transportation (community level). With this information, investigators then offered clinics a menu of EBIs and strategies to address barriers at each level. Clinics selected individually tailored MLIs, including improvement of patient education materials, provision of provider education (resulting in increased knowledge, p = .003), enhancement of electronic health record (EHR) systems and development of clinic screening protocols, and implementation of community CRC awareness events, all of which promoted stool-based screening (i.e., FIT or FIT-DNA). Variability among clinics, including differences in EHR systems, was the most salient barrier to EBI implementation, particularly in terms of tracking follow-up of positive screening results, whereas the development of clinic-wide screening protocols was found to promote fidelity to EBI components. Conclusions Lessons learned from year 1 included increased recognition of variability among the clinics and how they function, appreciation for clinic staff and provider workload, and development of strategies to utilize EHR systems. These findings necessitated a modification of study design for subsequent years. Trial registration Trial NCT04427527 is registered at https://clinicaltrials.gov and was registered on June 11, 2020.

Since the late ‘90 s, energy drink consumption has increased. The purpose of this investigation was to examine energy drink expectancies of college students. Participants: The university registrar ...

Background Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis. Objectives The aim of our study was to determine the association of these markers’ serum levels on lung function and the patients’ quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis. Methods 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King’s Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay. Results Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p Conclusions Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF.

Seventy-six FDA-approved oncology drugs and emerging therapeutics were evaluated in 25 multiple myeloma (MM) and 15 non-Hodgkin’s lymphoma cell lines and in 113 primary MM samples. Ex vivo drug sensitivities were mined for associations with clinical phenotype, cytogenetic, genetic mutation, and transcriptional profiles. In primary MM samples, proteasome inhibitors, dinaciclib, selinexor, venetoclax, auranofin, and histone deacetylating agents had the broadest cytotoxicity. Of interest, newly diagnosed patient samples were globally less sensitive especially to bromodomain inhibitors, inhibitors of receptor tyrosine kinases or non-receptor kinases, and DNA synthesis inhibitors. Clustering demonstrated six broad groupings of drug sensitivity linked with genomic biomarkers and clinical outcomes. For example, our findings mimic clinical observations of increased venetoclax responsiveness in t(11;14) patients but also identify an increased sensitivity profile in untreated patients, standard genetic risk, low plasma cell S-Phase, and in the absence of Gain(1q) and t(4;14). In contrast, increased ex vivo responsiveness to selinexor was associated with biomarkers of poor prognosis and later relapse patients. This “direct to drug” screening resource, paired with functional genomics, has the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders.

INTRODUCTION Few studies have examined the effects of racial segregation on colorectal cancer (CRC) outcomes, and none has determined whether rurality moderates the effect of racial segregation on CRC mortality. We examined whether the effect of segregation on CRC mortality varied by rurality in the Mississippi Delta Region, an economically distressed and historically segregated region of the United States. METHODS We used data from the US Census Bureau and the 1999-2018 Surveillance, Epidemiology, and End Results (SEER) program to estimate mixed linear regression models in which CRC mortality rates among Black and White residents in Delta Region counties (N = 252) were stratified by rurality and regressed on White-Black residential segregation indices and 4 socioeconomic control variables. RESULTS Among Black residents, CRC mortality rates in urban counties were a function of a squared segregation term (b = 162.78, P = .01), indicating that the relationship between segregation and CRC mortality was U-shaped. Among White residents, main effects of annual household income (b = 29.01, P = .04) and educational attainment (b = 34.58, P = .03) were associated with CRC mortality rates in urban counties, whereas only annual household income (b = 19.44, P = .04) was associated with CRC mortality rates in rural counties. Racial segregation was not associated with CRC mortality rates among White residents. CONCLUSION Our county-level analysis suggests that health outcomes related to racial segregation vary by racial, contextual, and community factors. Segregated rural Black communities may feature stronger social bonds among residents than urban communities, thus increasing interpersonal support for cancer prevention and control. Future research should explore the effect of individual-level factors on colorectal cancer mortality.