The advent of modern, high-speed electron detectors has made the collection of multidimensional hyperspectral transmission electron microscopy datasets, such as 4D-STEM, a routine. However, many microscopists find such experiments daunting since analysis, collection, long-term storage, and networking of such datasets remain challenging. Some common issues are their large and unwieldy size that often are several gigabytes, non-standardized data analysis routines, and a lack of clarity about the computing and network resources needed to utilize the electron microscope. The existing computing and networking bottlenecks introduce significant penalties in each step of these experiments, and thus, real-time analysis-driven automated experimentation for multidimensional TEM is challenging. One solution is to integrate microscopy with edge computing, where moderately powerful computational hardware performs the preliminary analysis before handing off the heavier computation to high-performance computing (HPC) systems. Here we trace the roots of computation in modern electron microscopy, demonstrate deep learning experiments running on an edge system, and discuss the networking requirements for tying together microscopes, edge computers, and HPC systems.

The myotendinous junction (MTJ) is a highly specialized region of the locomotor apparatus. Here, we investigated the ultrastructural and molecular effects in the MTJ region after static stretching prior to the ladder-based resistance training. Thirty-two male, 60-day old Wistar rats were divided into four groups: Sedentary, Resistance Training, Stretching, and Stretching-Resistance Training. The gastrocnemius muscle was processed for transmission electron microscopy techniques and Western blot assay. We observed that the static stretching prior to the ladder-based resistance training increased the MTJ components, the fibroblast growth factor (FGF)-2 and FGF-6 protein expression. Also, we demonstrated the lower transforming growth factor expression and no difference in the lysyl oxidase expression after combined training. The MTJ alterations in response to combined training demonstrate adaptive mechanisms which can be used for the prescription or development of methods to reduce or prevent injuries in humans and promote the myotendinous interface benefit.

Theories of early cooperation in human society often draw from a small sample of ethnographic studies of surviving populations of hunter–gatherers, most of which are now sedentary. Borneo hunter–gatherers (Punan, Penan) have seldom figured in comparative research because of a decades-old controversy about whether they are the descendants of farmers who adopted a hunting and gathering way of life. In 2018 we began an ethnographic study of a group of still-nomadic hunter–gatherers who call themselves Punan Batu (Cave Punan). Our genetic analysis clearly indicates that they are very unlikely to be the descendants of neighbouring agriculturalists. They also preserve a song language that is unrelated to other languages of Borneo. Dispersed travelling groups of Punan Batu with fluid membership use message sticks to stay in contact, co-operate and share resources as they journey between rock shelters and forest camps. Message sticks were once widespread among nomadic Punan in Borneo, but have largely disappeared in sedentary Punan villages. Thus the small community of Punan Batu offers a rare glimpse of a hunting and gathering way of life that was once widespread in the forests of Borneo, where prosocial behaviour extended beyond the face-to-face community, facilitating successful collective adaptation to the diverse resources of Borneo's forests.

Static stretching provides benefits to the range of motion, modulates intramuscular connective tissue, and is incorporated into warm-up exercises. In this study, we present the effects in the motor endplate and belly muscle resulting from previous static stretching to climbing training. Twenty-four adult male Wistar rats were divided into four groups (n = 6 each): Sedentary (Sed), Climbing (Clb), Static stretching (Ss), and Static stretching prior to climbing (Ssc). The animals (Clb, Ss, and Ssc groups) were subjected to a training protocol 3×/week for 8 weeks, and the Ssc group was subjected to the Ss and Clb protocols in the same session. Samples from the animals were processed for immunostaining, histochemistry, and light microscopy. The Clb group presented a higher motor endplate; the Ss group presented no changes in the motor endplate; and the Ssc group demonstrated a higher compactness. We concluded that static stretching prior to the climbing protocol maintained the density of the motor endplate and increased the compactness of the neuromuscular junction structure. Also, there was a reduction in the myofibers’ diameter (Type I and IIa), an increase in myofibrillar densities (Type I and IIx, and total), and the reorganization of the myonuclei and the interstitium.

European orthohantaviruses (Puumala orthohantavirus (PUUV); Dobrava-Belgrade orthohantavirus (DOBV), genotype Kurkino; Tula orthohantavirus (TULV)), and Leptospira spp. are small mammal-associated zoonotic pathogens that cause diseases with potentially similar symptoms in humans. We investigated the frequency of Leptospira spp. and hantavirus single and double infections in small mammals from 22 sites in Thuringia, central Germany, during 2017. TULV infections were detected at 18 of 22 sites (mean prevalence 13.8%, 93/674). PUUV infections were detected at four of 22 sites (mean prevalence 1.5%, 7/471), and respective PUUV sequences formed a novel phylogenetic clade, but DOBV infections were not detected at all. Leptospira infections were detected at 21 of 22 sites with the highest overall prevalence in field voles (Microtus agrestis) with 54.5% (6/11) and common voles (Microtus arvalis) with 30.3% (205/676). Leptospira–hantavirus coinfections were found in 6.6% (44/671) of common voles but only in two of 395 bank voles. TULV and Leptospira coinfection probability in common voles was driven by individual (age) and population-level factors. Coinfections seemed to be particularly associated with sites where Leptospira spp. prevalence exceeded 35%. Future investigations should evaluate public health consequences of this strong spatial clustering of coinfections.

Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.

Attention Deficit Hyperactivity Disorder (ADHD) is a serious risk factor for co-occurring psychiatric disorders and negative psychosocial consequences in adulthood. Given this background, there is great need for an effective treatment of adult ADHD patients.

Therefore, our research group has conducted a first controlled randomized multicenter study on the evaluation of disorder-tailored DBT-based group program in adult ADHD compared to a psychophar-macological treatment.

Between 2007 and 2010, in a four-arm-design 433 patients were randomized to a manualized dialectical behavioural therapy (DBT) based group program plus methylphenidate or placebo or clinical management plus methylphenidate or placebo with weekly sessions in the first twelve weeks and monthly sessions thereafter. Therapists are graduated psychologists or physicians. Treatment integrity is established by independent supervision. Primary endpoint (ADHD symptoms measured by the Conners Adult ADHD Rating Scale) is rated by interviewers blind to the treatment allocation (Current Controlled Trials ISRCTN54096201). The trial is funded by the German Federal Ministry of Research and Education (01GV0606) and is part of the German network for the treatment of ADHD in children and adults (ADHD-NET). In the lecture the first data of our interim analysis are presented (baseline data, results of treatment compliance and adherence).

The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together $60+$ programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.

On many Australian commercial pig farms, groups of growing pigs are mass-medicated through their drinking water with selected antimicrobials for short periods to manage herd health. However, delivery of medication in drinking water cannot be assumed to deliver an equal dose to all animals in a group. There is substantial between-animal variability in systemic exposure to an antimicrobial (i.e. the antimicrobial concentration in plasma), resulting in under-dosing or over-dosing of many pigs. Three sources of this between-animal variability during a water medication dosing event are differences in: (1) concentration of the active constituent of the antimicrobial product in water available to pigs at drinking appliances in each pen over time, (2) medicated water consumption patterns of pigs in each pen over time, and (3) pharmacokinetics (i.e. oral bioavailability, volume of distribution and clearance between pigs and within pigs over time). It is essential that factors operating on each farm that influence the range of systemic exposures of pigs to an antimicrobial are factored into antimicrobial administration regimens to reduce under-dosing and over-dosing.

Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.

We examined the functions of mothers’ speech to infants during two tasks – book-sharing and bead-stringing – in low-income, ethnically diverse families. Mexican, Dominican, and African American mothers and their infants were video-recorded sharing wordless books and toy beads in the home when infants were aged 1;2 and 2;0. Mothers’ utterances were classified into seven categories (labels/descriptions, emotion/state language, attention directives, action directives, prohibitions, questions, and vocal elicitations) which were grouped into three broad language functions: referential language, regulatory language, and vocalization prompts. Mothers’ ethnicity, years of education, years living in the United States, and infant sex and age related to mothers’ language functions. Dominican and Mexican mothers were more likely to use regulatory language than were African American mothers, and African American mothers were more likely to use vocalization prompts than were Latina mothers. Vocalization prompts and referential language increased with mothers’ education and Latina mothers’ years living in the United States. Finally, mothers of boys used more regulatory language than did mothers of girls. Socio-cultural and developmental contexts shape the pragmatics of mothers’ language to infants.

Background: Chronic intravenous immunoglobulin (IVIg) is used to treat refractory myasthenia gravis (MG). This subgroup analysis evaluated response to eculizumab in patients receiving chronic IVIg before entry to REGAIN, a phase 3, randomized, double-blind, placebo-controlled study of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized MG. Methods: IVIg was only permitted during REGAIN as rescue therapy; previously treated patients underwent a 4-week washout before randomization. Patients included in this analysis had received chronic IVIg ≥4 times in 1 year, with ≥1 dose within 6 months before REGAIN entry. Exacerbations and MG status changes were assessed. Results: Eighteen patients were evaluated; four experienced exacerbations (eculizumab-treated, 1/9; placebo-treated, 3/9). Clinically relevant improvements were larger with eculizumab than placebo, respectively (mean change, standard deviation [SD]: MG Activities of Daily Living score [MG-ADL], -5.3 [4.0] vs -2.1 [2.8]; Quantitative MG score [QMG], -4.1 [6.1] vs -1.3 [3.5]). More patients receiving eculizumab (7/9) had clinically meaningful responses (MG-ADL ≥3 and/or QMG ≥5 points) than those receiving placebo (3/9). Eculizumab safety was consistent with previous reports. Interim data from the open-label extension of REGAIN will be presented. Conclusions: In patients previously receiving chronic IVIg, eculizumab showed a trend toward meaningful clinical improvements and fewer exacerbations compared with placebo. (NCT01997229, NCT02301624).

Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.

Background: Patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (MG) unresponsive to conventional treatment experience greater disease burden than responsive patients. This is partly due to exacerbations, which may result in significant healthcare resource utilization. Eculizumab is well tolerated and gives clinically meaningful benefits in these patients. We evaluated the effect of long-term eculizumab treatment on exacerbations, hospitalizations and rescue therapy in the REGAIN study and its open-label extension. Methods: Exacerbations were defined as clinical worsening/deterioration, MG crises or rescue therapy usage; pre-study exacerbations/hospitalizations were defined from patient records. Event rates adjusted for patient-years were calculated for all patients in the pre-study year, patients receiving placebo during REGAIN, and patients receiving eculizumab during REGAIN and its open-label extension (median exposure, 27.5 months [range, 22 days–42.8 months]); rates were compared using a Poisson regression model. Results: Eculizumab treatment reduced exacerbations by 65% (p=0.0057), hospitalizations by 71% (p=0.0316) and rescue therapy use by 66% (p=0.0072) versus placebo. Eculizumab treatment reduced exacerbations by 74% and hospitalizations by 83% (both p<0.0001) versus the pre-study year. Conclusions: Long-term eculizumab treatment reduces disease burden and healthcare resource utilization, demonstrating continuing improvements in clinical endpoints that lead to additional meaningful outcomes for patients with AChR+ generalized MG. (NCT01997229, NCT02301624).

We describe an algorithm that can fit the properties of the dwarf galaxy progenitor of a tidal stream, given the properties of that stream. We show that under ideal conditions (the Milky Way potential, the orbit of the dwarf galaxy progenitor, and the functional form of the dwarf galaxy progenitor are known exactly), the density and angular width of stars along the stream can be used to constrain the mass and radial profile of both the stellar and dark matter components of the progenitor dwarf galaxy that was ripped apart to create the stream. Our provisional fit for the parameters of the dwarf galaxy progenitor of the Orphan Stream indicates that it is less massive and has fewer stars than previous works have indicated.