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Abstract Ribosomal DNA (rDNA) repeats harbor ribosomal RNA (rRNA) genes and intergenic spacers (IGS). RNA polymerase (Pol) I transcribes rRNA genes yielding rRNA components of ribosomes. IGS-associated Pol II prevents Pol I from excessively synthesizing IGS non-coding RNAs (ncRNAs) that can disrupt nucleoli and rRNA production. Here, compartment-enriched proximity-dependent biotin identification (compBioID) revealed the TATA-less-promoter-binding TBPL1 and transcription-regulatory PAF1 with nucleolar Pol II. TBPL1 localizes to TCT motifs, driving Pol II and Pol I and maintaining its baseline ncRNA levels. PAF1 promotes Pol II elongation, preventing unscheduled R-loops that hyper-restrain IGS Pol I-associated ncRNAs. PAF1 or TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. In PAF1-deficient cells, repressing unscheduled IGS R-loops rescues nucleolar organization and rRNA production. Depleting IGS Pol I-dependent ncRNAs is sufficient to compromise nucleoli. We present the nucleolar interactome of Pol II and show that its regulation by TBPL1 and PAF1 ensures IGS Pol I ncRNAs maintaining nucleolar structure and function.

Context: Evidence suggests that very few people with learning disabilities in England rent their own homes through the private or social housing rental sector. This is despite the fact that this group of people routinely say they would like more choice and control over where they live. We hypothesise that support from adult social care may benefit people to take up and sustain tenancies in this sector. Objective(s): This paper draws on original and empirical research with people with learning disabilities who do rent, and who are at the margins of social care eligibility, to understand more about their support needs from adult social care in relation to renting a home. Method(s): Qualitative, on-line interviews with 35 people with learning disabilities who rent their own homes in England. Findings: Renting a place to live was working relatively well for the people in the study. There were, however, some important and often unmet needs in relation to managing a tenancy. The amount of social care support people received relating to their housing and tenancy varied with no apparent reason for the variation. Some people described a decline in support and others referenced the cost of social care support charges. Housing and social care support was only very rarely joined up. The paper suggests that there is a potentially untapped source of housing options in the rented sector, but that social care support could play a greater role in supporting renters over time. Limitations: We did not manage to recruit many people who rented in the private rented sector compared with renting from social housing organisations. Our recruitment resulted in a majority of white respondents and a more diverse group would have been beneficial. Most of our respondents were recruited via self-advocacy organisations and it is conceivable that their links with groups that offered support meant that their experiences might not be representative of the wider population of people with learning disabilities. Implications: Choice about where to live – and where to call home is as important as ever but barriers remain for people with learning disabilities. We suggest that there is an important and preventative role for adult social care in offering, even sometimes quite small, packages of support to enter into and maintain a tenancy agreement.

Abstract Manipulating the spin state of thin layers of superconducting material is a promising route to generate dissipationless spin currents in spintronic devices. Approaches typically focus on using thin ferromagnetic elements to perturb the spin state of the superconducting condensate to create spin-triplet correlations. We have investigated simple structures that generate spin-triplet correlations without using ferromagnetic elements. Scanning tunneling spectroscopy and muon-spin rotation are used to probe the local electronic and magnetic properties of our hybrid structures, demonstrating a paramagnetic contribution to the magnetization that partially cancels the Meissner screening. This spin-orbit generated magnetization is shown to derive from the spin of the equal-spin pairs rather than from their orbital motion and is an important development in the field of superconducting spintronics.

BackgroundEvidence shows relaxation techniques reactivate the parasympathetic nervous system (PNS) following physiological stressors such as exercise. As such, these techniques may be useful following exercise training of high intensity sports, like collegiate football.PurposeTo evaluate the impact of mindfulness and rest activities on PNS reactivation following training sessions, in a sample of Division-I collegiate, male football athletes.MethodsThis study employed a cross-sectional, pre-post experimental design among 38 football athletes. Following three training sessions, each separated by one week, athletes were exposed to three groups: mindfulness, rest, and no-intervention. Athletes in the mindfulness group laid supine in a darkened room, while performing 15 min of guided breathing and body scans. The rest group remained seated in a lighted room, performing 15 min of restful activities (e.g., talking). The no-intervention group was instructed to perform usual post-training activities (e.g., showering). Heart rate (HR), respiration rate (RR) and two HR variability (HRV) indices were measured via an armband monitor (Warfighter Monitor, Tiger Tech Solutions, Inc, Miami, FL) equipped with electrocardiographic and photoplethysmography capabilities. HRV indices included standard deviation of the N-N intervals (SDNN) and root mean square of successive RR interval differences (rMSSD). Within and between-group differences were determined via analysis of variance (ANOVA) and corrected for multiple comparisons familywise error.ResultsStatistically significant reductions in HR and RR were observed across all groups: −81.6, −66.4, −40.9 bpm and −31.7, −26.9, and −19.0 breaths⋅min−1, respectively. The mindfulness and rest groups exhibited a larger within-group reduction in HR and RR compared to the no-intervention group, p

Abstract The African savannah ecosystem is populated by nomadic pastoralists who herd livestock in the day and corral them at night in temporary enclosures, called bomas, to protect them. The number and distribution of bomas on the savannah is important from an ecological perspective and may have a significant impact on wildlife movement. However, no study has yet examined this relationship. Here, using very high‐resolution satellite imagery from two time periods, we quanitified changes in boma distribution and density across an area of 3377 km2 in the Laikipia‐Samburu ecosystem of northern Kenya between 2011 and 2019. To assess wildlife movement in relation to bomas, we used a GPS data set on African bush elephant Loxodonta africana movement from 27 collared matriarchs representing herds of 9–15, covering 112 467 hourly GPS fixes over 31 months between 2018 and 2020. Our results showed a more than 46% increase in the total number of human‐built structures between 2011 and 2019, the majority of which were bomas, representing a 21.9% increase in human‐modified land area. Elephants readily adjusted their foraging habits and itineraries in this habitat shared with humans, who were also nomadic in space and time. Assessing the night–day activity ratio, we found elephants move more nocturnally when in closer proximity to bomas, particularly during the dry season. This temporal separation means elephants avoid the times humans are active in and around bomas while still accessing required resources—water and forage. The temporal shift was stronger during the dry season when shared resources are scarce. Using daily travel distance as a metric, we show elephants moved further in closer proximity to bomas which was likely linked to the need to travel between forage patches. Given the rise in human settlements, understanding the consequences of animals' behavioral adjustments is critical to understand the long‐term population viability of elephant populations.

The autonomic nervous system (ANS) is profoundly affected by high intensity exercise. However, evidence is less clear on ANS recovery and function following prolonged bouts of high intensity exercise, especially in non-endurance athletes. Therefore, this study aimed to investigate the relationships between duration and intensity of acute exercise training sessions and ANS recovery and function in Division I football athletes. Fifty, male football athletes were included in this study. Subjects participated in 135 days of exercise training sessions throughout the 25-week season and wore armband monitors (Warfighter Monitor, Tiger Tech Solutions) equipped with electrocardiography capabilities. Intensity was measured via heart rate (HR) during an ‘active state’, defined as HR ≥ 85 bpm. Further, data-driven intensity thresholds were used and included HR

Exercising with elevated core temperatures may negatively affect autonomic nervous system (ANS) function. Additionally, longer training duration under higher core temperatures may augment these negative effects. This study evaluated the relationship between exercise training duration and 24 h ANS recovery and function at ≥37 °C, ≥38 °C and ≥39 °C core temperature thresholds in a sample of male Division I (D1) collegiate American football athletes. Fifty athletes were followed over their 25-week season. Using armband monitors (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA), core temperature (°C) and 24 h post-exercise baseline heart rate (HR), HR recovery and heart rate variability (HRV) were measured. For HRV, two time-domain indices were measured: the root mean square of the standard deviation of the NN interval (rMSSD) and the standard deviation of the NN interval (SDNN). Linear regression models were performed to evaluate the associations between exercise training duration and ANS recovery (baseline HR and HRV) and function (HR recovery) at ≥37 °C, ≥38 °C and ≥39 °C core temperature thresholds. On average, the athletes were 21.3 (± 1.4) years old, weighed 103.0 (±20.2) kg and had a body fat percentage of 15.4% (±7.8%, 3.0% to 36.0%). The duration of training sessions was, on average, 161.1 (±40.6) min and they ranged from 90.1 to 339.6 min. Statistically significant associations between training duration and 24 h ANS recovery and function were observed at both the ≥38.0 °C (baseline HR: β = 0.10 ± 0.02, R2 = 0.26, p < 0.0000; HR recovery: β = −0.06 ± 0.02, R2 = 0.21, p = 0.0002; rMSSD: β = −0.11 ± 0.02, R2 = 0.24, p < 0.0000; and SDNN: β = −0.16 ± 0.04, R2 = 0.22, p < 0.0000) and ≥39.0 °C thresholds (β = 0.39 ± 0.05, R2 = 0.62, p < 0.0000; HR recovery: β = −0.26 ± 0.04, R2 = 0.52, p < 0.0000; rMSSD: β = −0.37 ± 0.05, R2 = 0.58, p < 0.0000; and SDNN: β = −0.67 ± 0.09, R2 = 0.59, p < 0.0000). With increasing core temperatures, increases in slope steepness and strengths of the associations were observed, indicating accelerated ANS deterioration. These findings demonstrate that exercise training under elevated core temperatures (≥38 °C) may negatively influence ANS recovery and function 24 h post exercise and progressively worsen.

Introduction: Urinary tract infections (UTI) are a common reason for an emergency department (ED) visit. The majority of these patients are discharged directly home without a hospital admission. After discharge, emergency physicians have traditionally managed the care of the patient if a change is warranted (as a result of urine culture results). However, in recent years clinical pharmacists in the ED have largely incorporated this task into their standard practice. In our study, we aimed to 1) describe our unique process in having a pharmacist-led, urinary culture follow-up, and 2) compare it to our previous, more traditional process. Methods: In our retrospective study, we evaluated the impact of a pharmacist-led, urinary culture follow-up program after discharge from the ED. We included patients prior to and after the implementation of our new protocol to compare the differences. The primary outcome was time to intervention after urine culture result was released. Secondary outcomes included rate of documentation of intervention, appropriate interventions made, and repeat ED visits within 30 days. Results: We included a total of 265 unique urine cultures from 264 patients in the study: 129 cultures were from the period prior to implementation of the protocol, and 136 were from the post-implementation period. There were no significant differences between pre- and post-implementation groups for the primary outcome. Appropriate therapeutic intervention based on positive urine culture results was 16.3% in the pre-implementation group vs 14.7% in the post-implementation group (P=0.72). Secondary outcomes of time to intervention, documentation rates, and readmissions were similar between both groups. Conclusion: Implementation of a pharmacist-led, urinary culture follow-up program after discharge from the ED led to similar outcomes as a physician-run program. An ED pharmacist can successfully run a urinary culture follow-up program in an ED without physician involvement.

Current metrics like baseline heart rate (HR) and HR recovery fail in predicting overtraining (OT), a syndrome manifesting from a deteriorating autonomic nervous system (ANS). Preventing OT requires tracking the influence of internal physiological loads induced by exercise training programs on the ANS. Therefore, this study evaluated the predictability of a novel, exercise cardiac load metric on the deterioration of the ANS. Twenty male American football players, with an average age of 21.3 years and body mass indices ranging from 23.7 to 39.2 kg/m2 were included in this study. Subjects participated in 40 strength- and power-focused exercise sessions over 8 weeks and wore armband monitors (Warfighter Monitor, Tiger Tech Solutions) equipped with electrocardiography capabilities. Exercise cardiac load was the product of average training HR and duration. Baseline HR, HR variability (HRV), average HR, and peak HR were also measured. HR recovery was measured on the following day. HRV indices assessed included the standard deviation of NN intervals (SDNN) and root mean square of successive RR interval differences (rMSSD) Linear regression models assessed the relationships between each cardiac metric and HR recovery, with statistical significance set at α < 0.05. Subjects were predominantly non-Hispanic black (70%) and aged 21.3 (±1.4) years. Adjusted models showed that exercise cardiac load elicited the strongest negative association with HR recovery for previous day (β = −0.18 ± 0.03; p < 0.0000), one-week (β = −0.20 ± 0.03; p < 0.0000) and two-week (β = −0.26 ± 0.03; p < 0.0000) training periods compared to average HR (βetas: −0.09 to −0.02; p < 0.0000) and peak HR (βetas: −0.13 to −0.23; p < 0.0000). Statistically significant relationships were also found for baseline HR (p < 0.0000), SDNN (p < 0.0000) and rMSSD (p < 0.0000). Exercise cardiac load appears to best predict ANS deterioration across one- to two-week training periods, showing a capability for tracking an athlete’s physiological tolerance and ANS response. Importantly, this information may increase the effectiveness of exercise training programs, enhance performance, and prevent OT.

Fully restoring autonomic nervous system (ANS) function is paramount for peak sports performance. Training programs failing to provide sufficient recovery, especially during the in-season, may negatively affect performance. This study aimed to evaluate the influence of the physiological workload of collegiate football training on ANS recovery and function during the in-season. Football athletes recruited from a D1 college in the southeastern US were prospectively followed during their 13-week “in-season”. Athletes wore armband monitors equipped with ECG and inertial movement capabilities that measured exercise cardiac load (ECL; total heartbeats) and maximum running speed during and baseline heart rate (HR), HR variability (HRV) 24 h post-training. These metrics represented physiological load (ECL = HR·Duration), ANS function, and recovery, respectively. Linear regression models evaluated the associations between ECL, baseline HR, HRV, and maximum running speed. Athletes (n = 30) were 20.2 ± 1.5 years, mostly non-Hispanic Black (80.0%). Negative associations were observed between acute and cumulative exposures of ECLs and running speed (β = −0.11 ± 0.00, p < 0.0000 and β = −0.15 ± 0.04, p < 0.0000, respectively). Similarly, negative associations were found between baseline HR and running speed (β = −0.45 ± 0.12, 95% CI: −0.70, −0.19; p = 0.001). HRV metrics were positively associated with running speed: (SDNN: β = 0.32 ± 0.09, p < 0.03 and rMSSD: β = 0.35 ± 0.11, p < 0.02). Our study demonstrated that exposure to high ECLs, both acutely and cumulatively, may negatively influence maximum running speed, which may manifest in a deteriorating ANS. Further research should continue identifying optimal training: recovery ratios during off-, pre-, and in-season phases.

Background: Methamphetamine is an addictive stimulant that may induce symptoms of agitation and psychosis. The estimated rate of methamphetamine use is 6.6 per 1000 people. Currently, no treatment guidelines exist to support the optimal management of patients presenting with methamphetamine-induced agitation. Emergency department (ED) providers may prescribe various benzodiazepines (BZDs) and antipsychotics (APs) as first-line agents to stabilize these agitated patients. This study aims to determine the effectiveness of a protocol to guide management of this condition. Methods: This was a retrospective, pre- and poststudy conducted from July 2020 to March 2021 at a large academic medical center. A multidisciplinary protocol was designed to help manage methamphetamine-induced agitation in the ED. The primary outcome of the study was a reduction in the number of BZDs and APs used for the treatment of methamphetamine-induced agitation. This was measured by the incidence of overprescribing, defined as 3 or more APs or BZDs administered within 30 minutes. Secondary outcomes included the use of physical restraints, ED length of stay, and adverse events. Results: We did not observe a significantly lower incidence of overprescribing, adverse events, or ED length of stay when comparing pre- and postprotocol groups. A subgroup analysis demonstrated that when protocol was followed, there was a statistically significant reduction in overprescribing (P =.001). Discussion: We did not find any differences among our primary and secondary outcomes, which may be attributed to protocol nonadherence. Full compliance to the protocol may reduce the rate of overprescribing APs or BZDs in patients with methamphetamine-induced agitation.

BackgroundLoneliness is associated with many mental health conditions, as both a potential causal and an exacerbating factor. Richer evidence about how people with mental health problems experience loneliness, and about what makes it more or less severe, is needed to underpin research on strategies to help address loneliness.MethodsOur aim was to explore experiences of loneliness, as well as what helps address it, among a diverse sample of adults living with mental health problems in the UK. We recruited purposively via online networks and community organisations, with most interviews conducted during the COVID-19 pandemic. Qualitative semi-structured interviews were conducted with 59 consenting participants face-to-face, by video call or telephone. Researchers with relevant lived experience were involved at all stages, including design, data collection, analysis and writing up of results.FindingsAnalysis led to identification of four overarching themes: 1. What the word "lonely" meant to participants, 2. Connections between loneliness and mental health, 3. Contributory factors to continuing loneliness, 4. Ways of reducing loneliness. Central aspects of loneliness were lack of meaningful connections with others and lack of a sense of belonging to valued groups and communities. Some drivers of loneliness, such as losses and transitions, were universal, but specific links were also made between living with mental health problems and being lonely. These included direct effects of mental health symptoms, the need to withdraw to cope with mental health problems, and impacts of stigma and poverty.ConclusionsThe multiplicity of contributors to loneliness that we identified, and of potential strategies for reducing it, suggest that a variety of approaches are relevant to reducing loneliness among people with mental health problems, including peer support and supported self-help, psychological and social interventions, and strategies to facilitate change at community and societal levels. The views and experiences of adults living with mental health problems are a rich source for understanding why loneliness is frequent in this context and what may address it. Co-produced approaches to developing and testing approaches to loneliness interventions can draw on this experiential knowledge.

Summary: Here, we present a protocol using MATRIX (mass spectrometry analysis of active translation factors using ribosome density fractionation and isotopic labeling experiments) platform to investigate changes of the protein synthesis machinery in U87MG glioblastoma cells in response to the rocaglate silvestrol. This protocol describes steps to perform SILAC (stable isotope labeling by amino acids in cell culture), ribosome density fractionation, protein isolation, and mass spectrometry analysis. This approach can be applied to study any adaptive remodeling of protein synthesis machineries.For complete details on the use and execution of this protocol, please refer to Ho et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Residential solar installations are becoming increasingly popular among homeowners. However, renters and homeowners living in shared buildings cannot go solar as they do not own the shared spaces. Community-owned solar arrays and energy storage have emerged as a solution, which enables ownership even when they do not own the property or roof. However, such community-owned systems do not allow individuals to control their share for optimizing a home’s electricity bill. To overcome this limitation, inspired by the concept of virtualization in operating systems, we propose virtual community-owned solar and storage—a logical abstraction to allow individuals to independently control their share of the system. We argue that such individual control can benefit all owners and reduce their reliance on grid power. We present mechanisms and algorithms to provide a virtual solar and battery abstraction to users and understand their cost benefits. In doing so, our comparison with a traditional community-owned system shows that our AutoShare approach can achieve the same global savings of 43% while providing independent control of the virtual system. Further, we show that independent energy sharing through virtualization provides an additional 8% increase in savings to individual owners.

Assessing the numbers and distribution of at-risk megafauna such as the black rhino (Diceros bicornis) is key to effective conservation, yet such data are difficult to obtain. Many current monitoring technologies are invasive to the target animals and expensive. Satellite monitoring is emerging as a potential tool for very large animals (e.g., elephant) but detecting smaller species requires higher resolution imaging. Drones can deliver the required resolution and speed of monitoring, but challenges remain in delivering automated monitoring systems where internet connectivity is unreliable or absent. This study describes a model built to run on a drone to identify in situ images of megafauna. Compared with previously reported studies, this automated detection framework has a lower hardware cost and can function with a reduced internet bandwidth requirement for local network communication. It proposes the use of a Jetson Xavier NX, onboard a Parrot Anafi drone, connected to the internet throughout the flight to deliver a lightweight web-based notification system upon detection of the target species. The GPS location with the detected target species images is sent using MQ Telemetry Transport (MQTT), a lightweight messaging protocol using a publisher/subscriber architecture for IoT devices. It provides reliable message delivery when internet connection is sporadic. We used a YOLOv5l6 object detection architecture trained to identify a bounding box for one of five objects of interest in a frame of video. At an intersection over union (IoU) threshold of 0.5, our model achieved an average precision (AP) of 0.81 for black rhino (our primary target) and 0.83 for giraffe (Giraffa giraffa). The model was less successful at identifying the other smaller objects which were not our primary targets: 0.34, 0.25, and 0.42 for ostrich (Struthio camelus australis), springbok (Antidorcas marsupialis) and human respectively. We used several techniques to optimize performance and overcome the inherent challenge of small objects (animals) in the data. Although our primary focus for the development of the model was rhino, we included other species classes to emulate field conditions where many animal species are encountered, and thus reduce the false positive occurrence rate for rhino detections. To constrain model overfitting, we trained the model on a dataset with varied terrain, angle and lighting conditions and used data augmentation techniques (i.e., GANs). We used image tiling and a relatively larger (i.e., higher resolution) image input size to compensate for the difficulty faced in detecting small objects when using YOLO. In this study, we demonstrated the potential of a drone-based AI pipeline model to automate the detection of free-ranging megafauna detection in a remote setting and create alerts to a wildlife manager in a relatively poorly connected field environment.

BackgroundNeurofilament light chain (NfL) is an axonal cytoskeletal protein that is released into the extracellular space following neuronal or axonal injury associated with neurological conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and other diseases. NfL is detectable in the cerebrospinal fluid (CSF) and blood. Numerous studies on MS have demonstrated that NfL is correlated with disease activity, predicts disease progression, and is reduced by treatment with MS disease-modifying drugs, making NfL an attractive candidate to supplement existing clinical and imaging measures in MS. However, for NfL to achieve its potential as a clinically useful biomarker for clinical decision-making or drug development, a standardized, practical, and widely accessible assay is needed. Our objective was to develop a novel NfL assay on an automated, globally available immunoassay platform and validate its performance.MethodsA prototype NfL assay was first developed and evaluated on the ADVIA Centaur® XP immunoassay system from Siemens Healthineers. The lower limit of quantitation (LLoQ), within-lab precision, assay range, cross-reactivity with neurofilament medium and heavy chains, and effect of interfering substances were determined. NfL assay values in serum and CSF were compared with radiological and clinical disease activity measures in patients with MS and ALS, respectively. This assay was further optimized to utilize serum, plasma, and CSF sample types on the Atellica® IM system and transferred to Siemens' CLIA laboratory where it was analytically validated as a laboratory-developed test (LDT).ResultsIn this study, an LLoQ of 1.85 pg/mL, within-lab precision

Translatome remodelling controls stress-adaptive protein output. Here the authors reveal that in response to stimuli, eIF5A functions as a pH-regulated translation factor that responds to fermentation-induced acidosis affecting cellular metabolism.

Abstract Background The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. Methods MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. Results Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2–23.5%) and 22.3% (95% confidence interval 13.2–31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. Conclusions Similar to other Project ECHO evaluation results in the United States of America, Namibia’s Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation.

mRNA translation efficiency is regulated in response to stimuli. Here the authors employ mass spectrometry analysis of ribosome fractions and show that under hypoxia, oxygen-sensitive RNA binding proteins enhance the translation efficiency of glycolysis pathway transcripts.

Glacially- and magmatically-derived seismic events have been noted to heavily overlap in characteristics, thus there exists the potential for false-alarms or missed warnings at ice-covered volcanoes. Here we present the first study to specifically target icequakes at an ice-covered volcano in Southern Chile. Two months of broadband seismic data collected at Llaima volcano in 2015 were analyzed in order to quantify, characterize, and locate glacially-derived seismic events at one of the most active ice-covered volcanoes in the region. We find over 1,000 repeating seismic events across 11 families, the largest of which contains 397 events. Approximate locations and characteristics of the largest families lead us to conclude that these events were derived from persistent stick-slip motion along the ice-rock interface at the base of a glacier near the volcano summit. These results have implications for future seismic monitoring at Llaima volcano and other ice-covered active volcanoes in the region.

Acute limb ischemia (ALI) represents one of the most common emergent scenarios encountered by a vascular specialist. Despite expedient revascularization, high rates of limb loss are reported along with high mortality rates which are second only to ruptured abdominal aortic aneurysms. Surgical revascularization is standard of care. Endovascular techniques as an alternative have emerged to be appropriate first line therapy when addressing the threatened limb. We review the etiology and classification of ALI and current endovascular techniques and evidence to date in the management of patients acutely presenting with extremity ischemia.

Increasing Uganda’s low electrification rate is one of the country’s major challenges. Power service is essential to achieve socioeconomic development and poverty reduction, especially in rural areas. This paper shows the advantages of using an integrated (grid and off-grid) electrification model with high geospatial, temporal, and customer-class granularity as the Reference Electrification Model (REM). In universal electrification strategies, REM will help better ascertain the role of minigrids, jointly with grid extension, solar kits, and stand-alone systems. REM has been applied to the Southern Service Territory (SST) to determine the least-cost mix of electrification modes—grid extension, off-grid minigrids, and standalone systems—that satisfies the hourly demand requirements of each customer—residential, commercial, or industrial—considering its individual location. REM incorporates the existing grid layout, the hourly solar local profile, and the catalogs of actual components for network and generation designs. The paper shows that minigrids can provide grid-like service at a significantly lower cost in many circumstances and to a considerable extent. Therefore, minigrid strategies should play a more important role in electrification planning, both transitorily and on a permanent basis, particularly when the central grid suffers from frequent and prolonged blackouts.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a reduction in emergency department (ED) visits was seen nationally according to the US Centers for Disease Control and Prevention. However, no data currently exists for the impact of ED transfers to a higher level of care during this same time period. The primary objective of the study was to determine whether the COVID-19 pandemic affected the rate of non-COVID-19 transfers from a rural community ED. Methods: We completed a retrospective chart review of all ED patients who presented to Kingman Regional Medical Center in Kingman, Arizona, from March 1–June 31, 2019 and March 1–June 31, 2020. To ensure changes were not due to seasonal trends, we examined transfer rates from the same four-month period in 2019 and 2020. Patients were included in the study if they were transferred to an outside facility for a higher level of care not related to COVID-19. Results: Between the time periods studied there was a 25.33% (P = 0.001) reduction in total ED volume and a 21.44% (P = 0.009) reduction in ED transfers to a higher level of care. No statistical difference was noted in ED transfer volume following adjustment for decreased ED volumes. Transfers for gastroenterology (45%; P = 0.021), neurosurgery (29.2%; P = 0.029), neurology (76.3%; P < 0.001), trauma (37.5%; P = 0.039), urology (41.8%; P = 0.012), and surgery (56.3%; P = 0.028) all experienced a decrease in transfer rates during the time period studied. When gender was considered, males exhibited an increased rate of transfers to psychiatric facilities (P = 0.018). Conclusion: Significant reductions in both ED volume and transfers have coincided with the emergence of the COVID-19 pandemic. Further research is needed to determine how the current pandemic has affected patient care.

Routinely censusing rhinoceros’ populations is central to their conservation and protection from illegal killing. In Namibia, both white (Ceratotherium simum) and black (Diceros bicornis) rhinoceros occur on private land, in the latter case under a custodianship program of the Namibian Ministry of Environment and Tourism (MET). Black rhinoceros custodian landowners are responsible for the protection of the rhinoceroses on their land and are required to report regularly to the MET. Monitoring imposes a financial burden on custodians yet many of the techniques used involve expensive monitoring techniques that include the need for aerial support and/or animal instrumentation. During May and June 2018, WildTrack undertook a pilot study to census black and white rhinoceros on three private custodianship properties in Namibia. We tested three footprint identification methods for obtaining estimates of rhinoceros populations in an effort to provide less costly alternative monitoring options to rhinoceros custodians. The first was a full monitoring protocol with two components: (a) tracking each individual animal and matching them to their footprints, (b) identifying those individuals from the heel lines on the prints. The second method used simple visual heel line identification ex-situ, and the third method used just an objective footprint identification technique. These methods offer different options of fieldwork labour and cost and were designed to offer monitoring options to custodians that provided information about rhinoceros movement and location, with minimal disturbance to the rhinoceros, and best matched their human and economic resources. In this study, we describe the three methods and report the results of the pilot study to compare and evaluate their utility for rhinoceros monitoring. The first method successfully matched each trail photographed to a known rhinoceros at each site. When the other two methods disagreed with the first, they did so by failing to match single trails to a known rhinoceros, thereby creating fictitious identities consisting of a single trail. This failure occurred twice in one application, but otherwise at most once. We expect this failure can be eliminated through more stringent criteria for collecting photographs of footprints. We also briefly compare the use of footprint monitoring with other commonly used monitoring techniques. On this basis, landowners hosting rhinoceros can evaluate which method best suits their needs and resources.

Magnetic metamaterials can be designed to provide models of frustrated systems that allow theoretical predictions to be experimentally tested. Here the authors realise a 2D XY model with dipolar interactions and find behaviour consistent with predictions of a low-temperature ordered state.

Summary: The eukaryotic translation initiation factor 5B (eIF5B) is a homolog of IF2, an ancient translation factor that enables initiator methionine-tRNAiMet (met-tRNAiMet) loading on prokaryotic ribosomes. While it can be traced back to the last universal common ancestor, eIF5B is curiously dispensable in modern aerobic yeast and mammalian cells. Here, we show that eIF5B is an essential element of the cellular hypoxic cap-dependent protein synthesis machinery. System-wide interrogation of dynamic translation machineries by MATRIX (mass spectrometry analysis of active translation factors using ribosome density fractionation and isotopic labeling experiments) demonstrated augmented eIF5B activity in hypoxic translating ribosomes. Global translatome studies revealed central carbon metabolism, cellular hypoxic adaptation, and ATF4-mediated stress response as major eIF5B-dependent pathways. These primordial processes rely on eIF5B even in the presence of oxygen and active eIF2, the canonical recruiter of met-tRNAiMet in eukaryotes. We suggest that aerobic eukarya retained eIF5B/IF2 to remodel anaerobic pathways during episodes of oxygen deficiency. : Ho et al. employed MATRIX to demonstrate that eIF5B is an essential hypoxic translation factor that facilitates met-tRNAiMet delivery to ribosomes, serving as the hypoxic surrogate of the textbook eIF2. Aerobic eukarya likely retained eIF5B for the oxygen-dependent regulation of central carbon metabolism and hypoxic survival. Keywords: eIF5B, IF2, translation, carbon metabolism, glycolysis, evolution, hypoxia, MATRIX, ATF4, stress

This year marks the 20th anniversary of the discovery that the nucleolus can temporarily immobilize proteins, a process known as nucleolar sequestration. This review reflects on the progress made to understand the physiological roles of nucleolar sequestration and the mechanisms involved in the immobilization of proteins. We discuss how protein immobilization can occur through a highly choreographed amyloidogenic program that converts the nucleolus into a large fibrous organelle with amyloid-like characteristics called the amyloid body (A-body). We propose a working model of A-body biogenesis that includes a role for low-complexity ribosomal intergenic spacer RNA (rIGSRNA) and a discrete peptide sequence, the amyloid-converting motif (ACM), found in many proteins that undergo immobilization. Amyloid bodies provide a unique model to study the multistep assembly of a membraneless compartment and may provide alternative insights into the pathological amyloidogenesis involved in neurological disorders.

Protein concentrations evolve under greater evolutionary constraint than mRNA levels. Translation efficiency of mRNA represents the chief determinant of basal protein concentrations. This raises a fundamental question of how mRNA and protein levels are coordinated in dynamic systems responding to physiological stimuli. This report examines the contributions of mRNA abundance and translation efficiency to protein output in cells responding to oxygen stimulus. We show that changes in translation efficiencies, and not mRNA levels, represent the major mechanism governing cellular responses to [O2] perturbations. Two distinct cap-dependent protein synthesis machineries select mRNAs for translation: the normoxic eIF4F and the hypoxic eIF4FH. O2-dependent remodeling of translation efficiencies enables cells to produce adaptive translatomes from preexisting mRNA pools. Differences in mRNA expression observed under different [O2] are likely neutral, given that they occur during evolution. We propose that mRNAs contain translation efficiency determinants for their triage by the translation apparatus on [O2] stimulus.

Summary: Amyloid bodies (A-bodies) are inducible membrane-less nuclear compartments composed of heterogeneous proteins that adopt an amyloid-like state. A-bodies are seeded by noncoding RNA derived from stimuli-specific loci of the rDNA intergenic spacer (rIGSRNA). This raises the question of how rIGSRNA recruits a large population of diverse proteins to confer A-body identity. Here, we show that long low-complexity dinucleotide repeats operate as the architectural determinants of rIGSRNA. On stimulus, clusters of rIGSRNA with simple cytosine/uracil (CU) or adenosine/guanine (AG) repeats spanning hundreds of nucleotides accumulate in the nucleolar area. The low-complexity sequences facilitate charge-based interactions with short cationic peptides to produce multiple nucleolar liquid-like foci. Local concentration of proteins with fibrillation propensity in these nucleolar foci induces the formation of an amyloidogenic liquid phase that seeds A-bodies. These results demonstrate the physiological importance of low-complexity RNA and repetitive regions of the genome often dismissed as “junk” DNA. : Wang et al. report the identification of stress-induced low-complexity ribosomal intergenic RNA that drive the formation of an amyloidogenic liquid-like phase. Concentration of proteins with fibrillation propensity by low-complexity RNA initiates an amyloidogenic program that confers A-body identity. Keywords: nucleolus, rDNA intergenic spacer, junk DNA, amyloidogenesis, phase separation, beta-amyloid, liquid-to-solid phase transition, complex coacervation, lncRNA, architectural RNA

A cognitively intensive companion service course has been introduced to the main fall general chemistry class at Cornell University. For years 2015 and 2016, priority students (those from groups under-represented and economically disadvantaged) show respectively improvement of +0.67 and +0.51 standard deviations in final course grade compared to priority students not in the program. Non-priority students show respectively a +0.66 and +0.62 standard deviation improvement. Progressive improvement (as measured by higher than expected Final Exam scores than what would have been expected solely from a given student's earlier Exam 1 score) demonstrates conclusively the service course's role in the enhanced outcomes. Progressive retention (as measured by the following year fall semester's organic chemistry exam scores compared to what would have been expected based on a given student's general chemistry final exam score) demonstrates that, on the average, the earlier observed progressive improvement is significantly retained in a chemistry course one year later. Preliminary retention statistics suggest a significant increase in first year to second year retention. A meta analysis of results from previously reported chemistry service courses indicate that such performance gains are difficult to achieve and hence common elements of the few effective programs may be of high value to the STEM education community.

This paper raises the question of how a proposition such as ‘Creative Citizenship’ might fit into the UK policy landscape. It begins by describing the appeal of such a concept to politicians keen to latch on to an idea that positions the electorate as creative, engaged and technologically astute. However, Creative Citizenship runs the dangers of being yet another fashionable, wide-ranging concept that political leaders tend to be ‘mesmerised’ by as they write up their election manifestos. Initiatives based on such ideas rarely meet with success and therefore for Creative Citizenship not to meet with the same fate it must be more clearly defined. The paper outlines a manifesto for Creative Citizenship that would allow for a more targeted application on those areas of public policy where the features of Creative Citizenship might be seen to be making a positive difference.

We developed methodology and built a portable reader to assess light transmittance in paper-based microfluidic devices in a highly sensitive, user-friendly and field-appropriate manner. By sandwiching the paper assay between micro-light-emitting diodes and micro-photodetectors, the reader quantifies light transmittance through the paper independent of ambient light conditions. To demonstrate the utility of the reader, we created a single-use paper-based microfluidic assay for measurement of alanine aminotransferase, an indicator of liver health in blood. The paper assay and reader system accurately differentiated alanine aminotransferase levels across the human reference range and demonstrated significant differences at clinically relevant cutoff values. Results were provided within 10 min and were automatically generated without complex image analysis. Performance of this point-of-care diagnostic rivals the accuracy of lab-based spectrometer tests at a fraction of the cost, while matching the timeliness of low-cost portable assays, which have historically shown lower accuracy. This combination of features allows flexible deployment of low cost and quantitative diagnostics to resource-poor settings. Keywords: Paper microfluidics, Colorimetric, Light transmission, Alanine aminotransferase, Enzymatic reactions, Continuous monitoring

Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the monocationic open-chain ammonium-ketone) co-exist in almost equal concentrations at physiological pH. We asked the question: Which of these forms is pharmacologically active? First, we investigated the pH dependence of anabaseine inhibition of [3H]-methylcarbamylcholine binding at rat brain α4β2 nicotinic acetylcholine receptors (nAChRs). These experiments indicated that one or both monocationic forms interact with the orthosteric binding site for ACh. However, since they occur at equal concentrations near physiological pH, we employed another approach, preparing a stable analog of each form and examining its agonist activities and binding affinities at several vertebrate brain and neuromuscular nAChRs. Only 2-(3-pyridyl)-1,4,5,6-tetrahydropyrimidine monohydrogen chloride (PTHP), the cyclic iminium analog, displayed nAChR potencies and binding affinities similar to anabaseine. The cyclic imine analog 2,3′-bipyridyl and the open-chain ammonium-ketone analog 5-methylamino-1-(3-pyridyl)-1-pentanone (MAPP), displayed ≤1% of the activity predicted if the one form was solely active. The lower potency of weakly basic 2,3′-bipyridyl can be explained by the presence of a small concentration of its monocationic form. Since the open chain ammonium-ketone monocationic form of anabaseine has some structural similarity to the neurotransmitter GABA, we also tested the ability of anabaseine and its 1,2-dehydropyrrolidinyl analog myosmine to activate a mammalian GABAA receptor, but no activity was detected. We conclude that the monocationic cyclic iminium is the form which avidly binds and activates vertebrate nAChRs.

Acne vulgaris may be improved by dietary factors that increase insulin sensitivity. We hypothesized that a low-glycemic index diet would improve facial acne severity and insulin sensitivity. Fifty-eight adolescent males (mean age ± standard deviation 16.5 ± 1.0 y and body mass index 23.1 ± 3.5 kg/m2) were alternately allocated to high or low glycemic index diets. Severity of inflammatory lesions on the face, insulin sensitivity (homeostasis modeling assessment of insulin resistance), androgens and insulin-like growth factor-1 and its binding proteins were assessed at baseline and at eight weeks, a period corresponding to the school term. Forty-three subjects (n = 23 low glycemic index and n = 20 high glycemic index) completed the study. Diets differed significantly in glycemic index (mean ± standard error of the mean, low glycemic index 51 ± 1 vs. high glycemic index 61 ± 2, p = 0.0002), but not in macronutrient distribution or fiber content. Facial acne improved on both diets (low glycemic index −26 ± 6%, p = 0.0004 and high glycemic index −16 ± 7%, p = 0.01), but differences between diets did not reach significance. Change in insulin sensitivity was not different between diets (low glycemic index 0.2 ± 0.1 and high glycemic index 0.1 ± 0.1, p = 0.60) and did not correlate with change in acne severity (Pearson correlation r = −0.196, p = 0.244). Longer time frames, greater reductions in glycemic load or/and weight loss may be necessary to detect improvements in acne among adolescent boys.

Mucin 1 (MUC1) is a transmembrane mucin glycoprotein that is over-expressed and aberrantly glycosylated in >80% of human pancreatic ductal adenocarcinoma (PDA) and is associated with poor prognosis. To understand the role of MUC1 in PDA, we have recently developed two mouse models of spontaneous PDA, one that expresses full-length human MUC1 transgene (KCM mice) and one that is null for MUC1 (KCKO mice). We have previously reported that KCM mice express high levels of myeloid derived suppressor cells (MDSCs) in their tumors and develop highly aggressive PDA. To further understand the underlying mechanism for high MDSC levels in KCM tumors, we generated primary cell lines from KCM and KCKO tumors. In this study, we report that MDSCs derived using KCM cells express significantly higher levels of arginase 1 and inducible nitric oxide synthase (markers associated with immune suppression) and lower levels of CD115 (a marker associated with maturation of myeloid cells) as compared to KCKO-derived MDSCs. Functionally, KCM-derived MDSCs secrete significantly higher levels of urea and nitric oxide when co-cultured with normal splenic cells as compared to KCKO-derived MDSCs. Data indicates that KCM-derived MDSCs remain immature and are more suppressive as compared to KCKO-derived MDSCs. This was further corroborated in vivo where MDSCs isolated from KCM-tumor bearing mice retained their immature state and were highly suppressive as compared to MDSCs derived from KCKO-tumor bearing mice. Finally, we show that KCM cells secrete significantly higher levels of prostaglandin E2 (PGE2,), a COX-2 metabolite and a known driver of suppressive MDSCs as compared to KCKO cells. Thus, inhibiting PGE2 with a specific COX-2 inhibitor reverses the immunosuppressive and immature phenotype of KCM-derived MDSCs. This is the first report that clearly suggests a functional role of pancreatic tumor-associated MUC1 in the development of functional MDSCs.

As diferenças entre a epopeia e o romance podem ser ressaltadas através da comparação da descrição do escudo de Aquiles, na Ilíada de Homero, e do Templo de Venus em The Knight’s Tale de Chaucer. Homero escreveu sobre o que definimos como detalhes da vida diária em situações contemporâneas das origens do poema; Chaucer, pelo contrário, transpõe os artifícios do amor cortes medieval para uma elaborada versão da mitologia grega: especificamente, a corte de Teseu em Atenas, transformada de tal modo que pareceria estranha a um grego da época clássica. Isso não significa que a epopeia e mais realista que o romance, mas que a epopeia e menos artificial e menos fantástica que o romance em sua visão de mundo.