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Transnational migration is seldom associated with Japan even though Japan has been dependent on immigrants for several generations. The research presented in this article explores a reform effort viewed as radical within the Japanese context that took place in a metropolitan school known for having one of the largest number of immigrant students in Japan, most of whom hail from Latin America, Southeast Asia, and China. While many of these “Newcomers” are of Japanese ancestry, absence from the homeland for two to four generations has left them without the cultural and linguistic skills to navigate the nuances of Japanese society. As a result, schools, which have never had to respond to the needs of immigrant youth, find themselves at a loss as to how to integrate young people whose parents have been drawn back from the Japanese diaspora through government policies designed to assuage the labor shortage of the 1980s and 1990s. Over the course of 5 months of ethnographic field work in the community in which this school is located the author offers insights gleaned from extensive time spent with social workers, translators, government workers, teachers, staff, students, parents, and community liaison volunteers, all of whom shared their frustrations and challenges with the education of immigrant youth within the context and constraints of Japanese schools.

The Himalayan Kingdom of Bhutan, where images of magical splendor obscure its challenges, provides a viewpoint from which to understand the contradictions that emerging economies face as they move towards mass education. Isolated from the outside world in every sense except for the mythologies that surround it, Bhutan is attempting to move from a basic agrarian societal framework as found in the feudal 1800s into the whirl of a technologically savvy twenty-first century. The demands for such a transition require educators and politicians at all levels to rethink the role of schooling and what it means to be educated in this country at this point in time. To provide guidance, the government set up a special task force, the Royal Education Council, to devise a curriculum and pedagogy that would equip young people with the skills to move into the future without forsaking their past. This ethnographic piece of research explores the challenges faced by teachers and principals in nine designated Beacon schools as they grapple within a historical context which views teachers as labourers, working under difficult conditions with minimal support. The work ends with the question of whether mass education might in fact move this country away from the traditional values that are perceived as making Bhutan special, if not unique. © 2013 Copyright Taylor and Francis Group, LLC.

Therapeutic efficacy with durable responses has been demonstrated with several antibody drugs that block key immune checkpoint receptors, including PD-1, PD-L1, and CTLA-4. Despite the success of these drugs, a substantial proportion of patients do not benefit. Targeting multiple inhibitory pathways simultaneously to augment anti-tumor immunity has proven to be a promising approach. The emergence of Repulsive Guidance Molecule b (RGMb), a ligand for PD-L2, as a novel co-inhibitory pathway in T cells, together with its regulation by the gut microbiome, encouraged the discovery and development of fully human anti-RGMb antibodies. Here, we describe phage display-derived monoclonal antibodies (mAbs) 2C11 and 5C10 that bind human RGMb with high affinities of 1.4 nM and 0.72 nM, respectively. Both mAbs 2C11 and 5C10 potently inhibited RGMb interaction with PD-L2. MAb 2C11 effectively inhibited RGMb interaction with bone morphogenetic proteins 2 and 4 (BMP2–4), while leaving RGMb interaction with Neogenin 1 (Neo1) unaffected. Conversely, mAb 5C10 disrupted RGMb interaction with Neo1 while maintaining RGMb binding to BMP2–4. These findings map the 2C11 epitope at the membrane-distal N-terminal region of RGMb, which coincides with both PD-L2- and BMP2–4-binding sites. The PD-L2 binding interface is likely positioned between RGMb’s N-terminal BMP-binding and C-terminal Neo1-binding regions. The in vivo activity of mAb 2C11 in combination with anti-PD-1 or anti-PD-L1 was tested in MC38 and B16-OVA cancer models and demonstrated synergistic effects by significantly enhancing anti-tumor responses. These properties make mAb 2C11 a promising candidate for therapeutic use to overcome immune checkpoint inhibitor resistances, warranting further exploration in clinical settings.

Objectives: There is a lack of knowledge about the challenges of researchers who continued in-person research during the early phases of the COVID-19 pandemic. Design: Electronic survey assessing work-related exposure to COVID-19, logistical challenges, and procedural changes during the first year of the COVID-19 pandemic on clinical research. Setting: National Heart, Lung, and Blood Institute-sponsored Prevention and Early Treatment of Acute Lung Injury Clinical Trial Network Centers. Subjects: Research staff at research Network Sites. Measurements and Main Results: The 37-question survey was completed by 277 individuals from 24 states between 29 September 2020, and 12 December 2020, yielding a response rate of 37.7%. Most respondents (91.5%) indicated that non-COVID-19 research was affected by COVID-19 research studies. In response to the COVID-19 pandemic, 20% of respondents were reassigned to different roles at their institution. Many survey takers were exposed to COVID-19 (56%), with more than 50% of researchers requiring a COVID-19 test and 8% testing positive. The fear of infection was 2.7-times higher compared to pre-COVID-19 times. Shortages of personal protective equipment were encountered by 34% of respondents, primarily due to lack of access to N95 masks, followed by gowns and protective eyewear. Personal protective equipment reallocation from research to clinical use was reported by 31% of respondents. Most of the respondents (88.5%), despite these logistical challenges, indicated their willingness to enroll COVID-19 patients. Conclusions: During the first year of the COVID-19 pandemic, members of the research network were engaged in COVID-19 research despite logistical challenges, limited access to personal protective equipment, and fear of exposure. The research network’s survey experience can inform ongoing policy discussions to create research enterprises that can dexterously refocus research to address the knowledge gaps associated with novel public health emergencies while mitigating the effect of pandemics on existing research projects and research personnel.

Background:. Marijuana use has been associated with vascular inflammation and clotting, resulting in endothelial damage and arteritis. As marijuana use rises in the United States, few studies have evaluated its impact on surgical outcomes and wound healing in free flap breast reconstruction. Methods:. A retrospective cohort study of patients undergoing abdominal free flap breast reconstruction between 2016 and 2022 at a large metropolitan healthcare system was performed. Patient demographics, comorbidities, procedural details, and complications were analyzed. Minor complications were defined as skin or fat necrosis not requiring intervention, nipple loss, any wound requiring management in the clinic, hematoma, and seroma. Major complications were defined as reoperation, flap loss, cardiac or thromboembolic events, and hospital readmission. Active marijuana users were those with marijuana use within 12 weeks of surgery. Results:. In total, 168 patients underwent 276 deep inferior epigastric artery-based flaps for breast reconstruction. There were 21 active marijuana users. There were no significant differences in patient demographics, cancer treatment, or minor and major complications. However, there were higher rates of active nicotine use (P = 0.001) and anxiety/depression amongst active marijuana users (P = 0.002). Active users had higher rates of bilateral breast reconstruction (P = 0.029), but no significant differences in other operative details. Conclusions:. Active marijuana use of unknown frequency may be safe in patients undergoing breast free flap reconstruction. Advising marijuana abstinence preoperatively may not alter patient outcomes. Further studies of greater sample size are needed to evaluate marijuana’s impact on outcomes associated with breast reconstruction using free flap.

Abstract The invasive Asian date mussel (Arcuatula senhousia) inhabits diverse global coastal environments, in some circumstances posing significant ecological and economic risks. Recently recorded in the Greater North Sea ecoregion, an established population has not previously been confirmed. Combining historical and field data, we provided baseline information from the UK and recorded colonisation in a variety of habitats. Gonadal development was assessed using the gonadosomatic index (GSI) to determine if an intertidal soft-sediment population is self-sustaining. Arcuatula senhousia records from subtidal muddy/mixed-sediment within a major estuarine system from 2007 to 2016 were also analysed. First detected in 2011, spatial distribution was variable across the years within the subtidal, with individuals found at 4–9 out of 25 sites, and densities per site varying from 10 to 290 individuals per m2. The intertidal population was, in part, associated with seagrass (Zostera spp.) and attached to bivalves. In marinas, individuals were attached to concrete tiles, associated with live Mytilus edulis, and to dead Ostrea edulis. Mean GSI from the intertidal population differed across months, peaking in July before declining in September/October, but with high inter-individual variability. Arcuatula senhousia is reproducing and maintaining viable populations. Using a natural capital approach, we identify the potential impacts on Europe’s functionally important habitats, fisheries and aquaculture if its spread continues.

Significance: The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies. Objective: The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19. Design: Multi-center retrospective observational study. Setting: The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan. Participants: Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48 h unless expired within 24 h. Exposure: Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither. Main outcome: The primary outcome was in-hospital mortality. Results: Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4–10 days), median age was 64 years (IQR:53–76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3–53). Overall in-hospital mortality was 18.1% (95% CI:16.6%–19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%–23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%–15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%–30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%–31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9–3.3]), white race (HR:1.7 [95% CI:1.4–2.1]), CKD (HR:1.7 [95%CI:1.4–2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1–2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4–3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p

Abstract Background Justice-involved youth have higher rates of sexually transmitted infections (STIs), and a higher prevalence of the associated sexual risk behaviors. Sexual risk behaviors are also associated with alcohol and drug use. Research suggests that a history of trauma is an important predictor of alcohol and drug use in youth offenders, and therefore is a likely contributor to sexual risk behavior in this population. The objective of this analysis is to determine the association of trauma, specifically, domestic violence and forced sex, to six sexual risk behaviors and a history of chlamydia among detained youth. Methods The analysis uses data from a convenience sample of detainees assenting to HIV testing conducted December 2016 – August 2017 using the state-certified Voluntary Counseling Testing and Referral (VCTR) process. Results Of the 379 youth that received VCTR at the facility, 308 (81.3%) were used in this analysis. Report of domestic violence was significantly associated with sex under the influence of alcohol and was also significantly associated with sex under the influence of marijuana. Forced sex was associated with a sexual partner of unknown HIV status. Conclusions Traumatic experiences were related to sexual risk behaviors in this analysis, and substance use was strongly implicated in the association. Trauma is known to be a catalyst to sexual risk behaviors, substance use, and delinquency in adolescence. Results support the findings of other investigators and re-iterate the need for trauma-informed interventions that can improve the life trajectories of detained youth.

Globally, environmental impacts and insecticide resistance are forcing pest control organizations to adopt eco-friendly and insecticide-free alternatives to reduce the risk of mosquito-borne diseases, which affect millions of people, such as dengue, chikungunya or Zika virus. We used, for the first time, a combination of human odor-baited mosquito traps (at 6.0 traps/ha), oviposition traps (7.2 traps/ha) and larval source management (LSM) to practically eliminate populations of the Asian tiger mosquito Aedes albopictus (peak suppression 93.0% (95% CI 91.7–94.4)) and the Southern house mosquito Culex quinquefasciatus (peak suppression 98.3% (95% CI 97.0–99.5)) from a Maldivian island (size: 41.4 ha) within a year and thereafter observed a similar collapse of populations on a second island (size 49.0 ha; trap densities 4.1/ha and 8.2/ha for both trap types, respectively). On a third island (1.6 ha in size), we increased the human odor-baited trap density to 6.3/ha and then to 18.8/ha (combined with LSM but without oviposition traps), after which the Aedes mosquito population was eliminated within 2 months. Such suppression levels eliminate the risk of arboviral disease transmission for local communities and safeguard tourism, a vital economic resource for small island developing states. Terminating intense insecticide use (through fogging) benefits human and environmental health and restores insect biodiversity, coral reefs and marine life in these small and fragile island ecosystems. Moreover, trapping poses a convincing alternative to chemical control and reaches impact levels comparable to contemporary genetic control strategies. This can benefit numerous communities and provide livelihood options in small tropical islands around the world where mosquitoes pose both a nuisance and disease threat.

Objective: The aim of the study was to investigate racial/ethnic differences in emergency care for patients with joint dislocation. Methods: We performed a secondary analysis of the dislocation component of the National Emergency Department Safety Study. Using a principal diagnosis of dislocation, we identified emergency department (ED) visits for joint dislocations in 53 urban EDs across 19 US states between 2003 and 2005. Quality of care was evaluated based on 9 guideline-concordant care measures. Results: Of the 1945 patients included in this analysis, 1124 (58%) were white; 561 (29%), black, and 260 (13%), Hispanic. One-third of the 53 EDs cared for 51% of minority patients. After multivariable adjustment, black patients were less likely to receive any analgesic treatment (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.51-0.90) or opioid treatment (OR, 0.64; 95% CI, 0.41-0.997), waited longer to receive analgesia (mean difference in time to analgesic treatment, 32 minutes; 95% CI, 16-52 minutes), and were less likely to receive reassessments of pain (OR, 0.49; 95% CI, 0.34-0.70) compared with white patients. There were no ethnic disparities in most of the care measures between Hispanic and white patients. There were no disparities in initial pain assessment, pre- and postprocedural neurovascular assessment, procedural monitoring, or success of joint reduction across the racial/ethnic groups. Conclusions: Black patients presenting to the ED with joint dislocations received lower quality of care in some, but not all, areas compared with white patients. Future interventions should target these areas to eliminate racial disparities in dislocation care. [ABSTRACT FROM AUTHOR]

Technology-enhanced patient simulation has emerged as an important new modality for teaching and learning in medicine. In particular, immersive simulation platforms that replicate the clinical environment promise to revolutionize medical education by enabling an enhanced level of safety, standardization, and efficiency across health-care training. Such an experiential approach seems unique in reliably catalyzing a level of emotional engagement that fosters immediate and indelible learning and allows for increasingly reliable levels of performance evaluation-all in a completely risk-free environment. As such, medical simulation is poised to emerge as a critical component of training and certification throughout health care, promising to fundamentally enhance quality and safety across disciplines. To encourage routine simulation-based practice as part of its core quality and safety mission, Massachusetts General Hospital now incorporates simulation resources within its historic medical library (est. 1847), located at the center of the campus. In this new model, learners go to the library not only to read about a patient's illness, but also to take care of their "patient." Such an approach redefines and advances the central role of the library on the campus and ensures that simulation-based practice is centrally available as part of everyday hospital operations. This article describes the reasons for identifying simulation as an institutional priority leading up to the Massachusetts General Hospital Bicentennial Celebration (1811-2011) and for creating a simulation-based learning laboratory within a hospital library. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVE: We describe the frequency of undesirable events among patients boarding at a single, urban, tertiary, teaching emergency department (ED) through retrospective chart abstraction. METHODS: This was a chart review of all patients admitted during 3 randomly selected days in 2003 (n=162) to track the frequency of undesirable events such as missed relevant home medications, missed laboratory test results, arrhythmias, or other adverse events. RESULTS: One hundred fifty-one charts were abstracted (93.2%); 27.8% had an undesirable event, 17.9% missed a relevant home medication, and 3.3% had a preventable adverse event. There was a higher frequency of undesirable events among older patients (35.9%, aged >50 years; 7.3%, aged 20 to 49 years; 28.6%, aged 0 to 19 years) and those with more comorbidities (44.4% among Charlson score >or=3; 30.8% score 2; 36.1% score 1; 14.5% score 0). CONCLUSION: A substantial frequency of undesirable events occurs while patients board in the ED. These events are more frequent in older patients or those with more comorbidities. Future studies need to compare the rates of undesirable events among patients boarding in the ED versus inpatient units. [ABSTRACT FROM AUTHOR]

BACKGROUND: Performance-based assessments are often not reliable enough to be used as the sole method for determining a grade. PURPOSE: Using more than 1 assessment format has several advantages and can improve the quality of the information used to calculate course grades. To achieve a valid and reliable total score representing a combination of multiple assessment formats requires appropriate weighting procedures. METHODS: The classical test theory rationale and methodology for appropriately weighting in-course assessments is presented. Two reliablility-related equations are used to make decisions about weighting for a computerized performance assessment and a pattern recognition multiple-choice exam. RESULTS: Using the equations presented, the outcomes of various weighting scenarios are graphically presented. This technique produced weights that allow the instructor to obtain acceptable reliability while retaining a substantial emphasis on performance assessment. CONCLUSION: The weights assigned to component tests used to derive a total score have important reliability and validity implications. Course instructors need to consider both empirical reliability and logical validity evidence in determining component weights. When used in conjunction with classical methods, objectively scored item formats can augment performance assessments and enhance overall validity and reliability. [ABSTRACT FROM AUTHOR]

Abstract Intuitively scientists accept that order can emerge from disorder and a significant amount of effort has been devoted over many years to demonstrate this. In metallic alloys and oxides, disorder at the atomic scale is the result of occupation at equivalent atomic positions by different atoms which leads to the material exhibiting a fully random or modulated scattering pattern. This arrangement has a substantial influence on the material’s properties, for example ionic conductivity. However it is generally accepted that oxides, such as defect fluorite as used for nuclear waste immobilization matrices and fuel cells, are the result of disorder at the atomic scale. To investigate how order at the atomic scale induces disorder at a larger scale length, we have applied different techniques to study the atomic composition of a homogeneous La 2 Zr 2 O 7 pyrochlore, a textbook example of such a structure. Here we demonstrate that a pyrochlore, which is considered to be defect fluorite, is the result of intricate disorder due to a random distribution of fully ordered nano-domains. Our investigation provides new insight into the order disorder transformations in complex materials with regards to domain formation, resulting in a concord of chemistry with crystallography illustrating that order can induce disorder.

Functional neuronal homeostasis has been studied in a variety of model systems and contexts. Many studies have shown that there are a number of changes that can be activated within individual cells or networks in order to compensate for perturbations or changes in levels of activity. Dissociating the cell autonomous from the network-mediated events has been complicated due to the difficulty of sparsely targeting specific populations of neurons in vivo. Here, we make use of a recent in vivo approach we developed that allows for the sparse labeling and manipulation of activity within superficial CGE-derived GABAergic interneurons. Expression of the inward rectifying potassium channel Kir2.1 cell-autonomously reduced neuronal activity and lead to specific developmental changes in their intrinsic electrophysiological properties and the synaptic input they received. In contrast to previous studies on homeostatic scaling of pyramidal cells, we did not detect any of the typically observed compensatory mechanisms in these interneurons. Rather, we instead saw a specific alteration of the kinetics of excitatory synaptic events within the reelin-expressing subpopulation of interneurons. These results provide the first in vivo observations for the capacity of interneurons to cell-autonomously regulate their excitability.

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Children's Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.

Abstract Background Cerebral cortex has a very large number of testosterone receptors, which could be a basis for sex differences in sensory functions. For example, audition has clear sex differences, which are related to serum testosterone levels. Of all major sensory systems only vision has not been examined for sex differences, which is surprising because occipital lobe (primary visual projection area) may have the highest density of testosterone receptors in the cortex. We have examined a basic visual function: spatial and temporal pattern resolution and acuity. Methods We tested large groups of young adults with normal vision. They were screened with a battery of standard tests that examined acuity, color vision, and stereopsis. We sampled the visual system’s contrast-sensitivity function (CSF) across the entire spatio-temporal space: 6 spatial frequencies at each of 5 temporal rates. Stimuli were gratings with sinusoidal luminance profiles generated on a special-purpose computer screen; their contrast was also sinusoidally modulated in time. We measured threshold contrasts using a criterion-free (forced-choice), adaptive psychophysical method (QUEST algorithm). Also, each individual’s acuity limit was estimated by fitting his or her data with a model and extrapolating to find the spatial frequency corresponding to 100% contrast. Results At a very low temporal rate, the spatial CSF was the canonical inverted-U; but for higher temporal rates, the maxima of the spatial CSFs shifted: Observers lost sensitivity at high spatial frequencies and gained sensitivity at low frequencies; also, all the maxima of the CSFs shifted by about the same amount in spatial frequency. Main effect: there was a significant (ANOVA) sex difference. Across the entire spatio-temporal domain, males were more sensitive, especially at higher spatial frequencies; similarly males had significantly better acuity at all temporal rates. Conclusion As with other sensory systems, there are marked sex differences in vision. The CSFs we measure are largely determined by inputs from specific sets of thalamic neurons to individual neurons in primary visual cortex. This convergence from thalamus to cortex is guided by cortex during embryogenesis. We suggest that testosterone plays a major role, leading to different connectivities in males and in females. But, for whatever reasons, we find that males have significantly greater sensitivity for fine detail and for rapidly moving stimuli. One interpretation is that this is consistent with sex roles in hunter-gatherer societies.

Abstract Background Because cerebral cortex has a very large number of testosterone receptors, we examined the possible sex differences in color appearance of monochromatic lights across the visible spectrum. There is a history of men and women perceiving color differently. However, all of these studies deal with higher cognitive functions which may be culture-biased. We study basic visual functions, such as color appearance, without reference to any objects. We present here a detailed analysis of sex differences in primary chromatic sensations. Methods We tested large groups of young adults with normal vision, including spatial and temporal resolution, and stereopsis. Based on standard color-screening and anomaloscope data, we excluded all color-deficient observers. Stimuli were equi-luminant monochromatic lights across the spectrum. They were foveally-viewed flashes presented against a dark background. The elicited sensations were measured using magnitude estimation of hue and saturation. When the only permitted hue terms are red (R) yellow (Y), green (G), blue (B), alone or in combination, such hue descriptions are language-independent and the hue and saturation values can be used to derive a wide range of color-discrimination functions. Results There were relatively small but clear and significant, differences between males and females in the hue sensations elicited by almost the entire spectrum. Generally, males required a slightly longer wavelength to experience the same hue as did females. The spectral loci of the unique hues are not correlated with anomaloscope matches; these matches are directly determined by the spectral sensitivities of L- and M-cones (genes for these cones are on the X-chromosomes). Nor are there correlations between loci of pairs of unique hues (R, Y, G, B). Wavelength-discrimination functions derived from the scaling data show that males have a broader range of poorer discrimination in the middle of the spectrum. The precise values for all the data depend on whether Newtonian or Maxwellian optics were used, but the sex differences were the same for both optical systems. Conclusion As with our associated paper on spatio-temporal vision, there are marked sex differences in color vision. The color-appearances we measured are determined by inputs from thalamic neurons (LGN) to individual neurons in primary visual cortex. This convergence from LGN to cortex is guided by the cortex during embryogenesis. We hypothesize that testosterone plays a major role, somehow leading to different connectivities for males and females: color appearance requires a re-combination and re-weighting of neuronal inputs from the LGN to the cortex, which, as we show, depends on the sex of the participant.

Abstract Background Current guidelines for rehabilitation of arm and hand function after stroke recommend that motor training focus on realistic tasks that require reaching and manipulation and engage the patient intensively, actively, and adaptively. Here, we investigated the feasibility of a novel robotic task-practice system, ADAPT, designed in accordance with such guidelines. At each trial, ADAPT selects a functional task according to a training schedule and with difficulty based on previous performance. Once the task is selected, the robot picks up and presents the corresponding tool, simulates the dynamics of the tasks, and the patient interacts with the tool to perform the task. Methods Five participants with chronic stroke with mild to moderate impairments (> 9 months post-stroke; Fugl-Meyer arm score 49.2 ± 5.6) practiced four functional tasks (selected out of six in a pre-test) with ADAPT for about one and half hour and 144 trials in a pseudo-random schedule of 3-trial blocks per task. Results No adverse events occurred and ADAPT successfully presented the six functional tasks without human intervention for a total of 900 trials. Qualitative analysis of trajectories showed that ADAPT simulated the desired task dynamics adequately, and participants reported good, although not excellent, task fidelity. During training, the adaptive difficulty algorithm progressively increased task difficulty leading towards an optimal challenge point based on performance; difficulty was then continuously adjusted to keep performance around the challenge point. Furthermore, the time to complete all trained tasks decreased significantly from pretest to one-hour post-test. Finally, post-training questionnaires demonstrated positive patient acceptance of ADAPT. Conclusions ADAPT successfully provided adaptive progressive training for multiple functional tasks based on participant's performance. Our encouraging results establish the feasibility of ADAPT; its efficacy will next be tested in a clinical trial.

Abstract Background Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data. Methods Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. Results Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c ≥ 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 ± 1.35 U/Kg to 0.88 ± 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 ± 2.51 U/Kg to 0.98 ± 2.58 U/Kg, p < 0.001). Conclusion In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.

Abstract Background Insulin glargine (glargine) and insulin NPH (NPH) are two basal insulin treatments. This study investigated the effect on glycaemic control of switching from a NPH-based regimen to a glargine-based regimen in 701 patients with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care data. Methods Data for this retrospective observational study were extracted from a UK primary care database (The Health Improvement Network). Patients were required to have at least 12 months of data before and after switching from NPH to glargine. The principal analysis was the change in HbA1c after 12 months treatment with glargine; secondary analyses included change in weight and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable reporting of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. Results After adjustment, both diabetic cohorts showed statistically significant reductions in mean HbA1c 12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with baseline HbA1c; patients with baseline HbA1c ≥ 8% had reductions of 0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant change in weight or total daily insulin dose while on glargine. The majority of patients received a basal-bolus regimen prior to and after the switch (mean 79.3% before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%, respectively in type 2 patients, p > 0.05). Conclusion In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.

Abstract Background Antenatal education (AE) started more than 30 years ago with the purpose of decreasing pain during childbirth. Epidural anaesthesia has achieved this objective, and the value of AE is therefore currently questioned. This article describes the protocol and process of a study designed to assess AE results today. Methods/Design A prospective study was designed in which a cohort of 616 nulliparous pregnant women attending midwife offices of the Basque Health Service were followed for 13 months. Three exposure groups were considered based on the number of AE sessions attended: (a) women attending no session, (b) women attending 1 to 4, and (c) women attending 5 or more sessions. Sociodemographic, personality, and outcome variables related to childbirth and breastfeeding were measured. It was expected 40% of pregnant women not to have participated in any AE session. However, 93% had attended at least one session. This low exposure variability decreased statistical power of the study as compared to the initially planned power. Despite this, there was a greater than 80% power for detecting as significant differences between exposure groups of, for instance, 10% in continuation of breastfeeding at one and a half months and in visits for false labour. Women attending more sessions were seen to have a mean higher age and educational level, and to belong to a higher socioeconomic group (p < 0.01). Follow-up was completed in 99% of participants. Discussion Adequate prior estimation of variability in the exposure under study is essential for designing cohort studies. Sociodemographic characteristics may play a confounding role in studies assessing AE and should be controlled in design and analyses. Quality control during the study process and continued collaboration from both public system midwives and eligible pregnant women resulted in a negligible loss rate.

Reports on developments related to medical care as of December 1999. Includes therapeutic powers of prayer; Smoke alarms' effectiveness in preventing accidental death in children caused by fire.

NIMH's mission is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. New imaging techniques hold great promise for improving our understanding of the pathophysiology of mental illnesses, stratifying patients for treatment selection, and developing a personalized medicine approach. Here, we highlight emerging and promising new technologies that are likely to be vital in helping NIMH accomplish its mission, the potential for utilizing multimodal approaches to study mental illness, and considerations for data analytics and data sharing., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Mental illnesses arise from dysfunction in the brain. Although numerous extraneural factors influence these illnesses, ultimately, it is the science of the brain that will lead to novel therapies. Meanwhile, our understanding of this complex organ is incomplete, leading to the oft-repeated trope that neuroscience has yet to make significant contributions to the care of individuals with mental illnesses. This review seeks to counter this narrative, using specific examples of how neuroscientific advances have contributed to progress in mental health care in the past and how current achievements set the stage for further progress in the future., Competing Interests: Declaration of interests K.D. is a member of the Cell editorial board., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The human brain undergoes rapid development during the first years of life. Beginning in utero, a wide array of biological, social, and environmental factors can have lasting impacts on brain structure and function. To understand how prenatal and early life experiences alter neurodevelopmental trajectories and shape health outcomes, several NIH Institutes, Centers, and Offices collaborated to support and launch the HEALthy Brain and Child Development (HBCD) Study. The HBCD Study is a multi-site prospective longitudinal cohort study, that will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Influenced by the success of the ongoing Adolescent Brain Cognitive Development SM Study (ABCD Study®) and in partnership with the NIH Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, the HBCD Study aims to establish a diverse cohort of over 7000 pregnant participants to understand how early life experiences, including prenatal exposure to addictive substances and adverse social environments as well as their interactions with an individual's genes, can affect neurodevelopmental trajectories and outcomes. Knowledge gained from the HBCD Study will help identify targets for early interventions and inform policies that promote resilience and mitigate the neurodevelopmental effects of adverse childhood experiences and environments., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Julia L. Zehr reports a relationship with Jazz Pharmaceuticals Inc that includes: equity or stocks. Co-author’s spouse is employed by Jazz Pharmaceuticals, Inc - JLZ If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier Ltd.)

Background: Squamous cell carcinoma of the prostate (SCCP) is a neoplasm that comprises fewer than 1% of all primary prostate cancer diagnoses. Given its rarity, there is a paucity of data regarding the treatment of this disease. The limited literature points to the potential of local therapy in conjunction with chemotherapy to improve patient mortality., Methods: Using the National Cancer Initiative's Surveillance, Epidemiology, and End Results (SEER) database, a retrospective review of patients diagnosed with primary SCCP between 2000 and 2018 was performed. Patient demographics, tumor characteristics, and patient outcomes based on treatment modality were analyzed. Univariate and survival analyses were conducted with p < 0.05 indicating statistical significance., Results: A total of 66 patients were identified. Five-year overall survival (5y OS) was 24%; mean and median survival were 2.2 years (1.8, 2.7) and 1.2 years (0.3, 2.1), respectively. Patients with Grade I or Grade II disease had an increased 5y OS of 55% (27%, 83%). In comparison, 5y OS was 13% (-2%, 29%) for patients with Grade III and Grade IV disease (p = 0.017). Analysis of 5y OS based on disease histology revealed patients with papillary SCC had a 5y OS of 50% [9.2%, 91%], compared to 21% [9%, 34%] for patients with SCC, not otherwise specified and 0% for those with lymphoepithelial carcinoma (p = 0.048). Analysis of 5y OS stratified by treatment modality revealed no statistically significant change with any treatment (surgery, radiotherapy, and chemotherapy). No difference in 5y OS was seen between those treated with radical prostatectomy versus external beam radiation therapy., Conclusions: The literature on SCCP remains sparse; the rarity of this disease limits analysis. While the investigation undertaken in this paper does not find any change in 5y OS regardless of treatment modality, the variation in 5y OS based on histologic classification of SCCP points to a potential route for the future treatment of this disease., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Skeletal muscle has a classic structure function relationship; both skeletal muscle microstructure and architecture are directly related to force generating capacity. Biopsy, the gold standard for evaluating muscle microstructure, is highly invasive, destructive to muscle, and provides only a small amount of information about the entire volume of a muscle. Similarly, muscle fiber lengths and pennation angles, key features of muscle architecture predictive of muscle function, are traditionally studied via cadaveric dissection. Noninvasive techniques such as diffusion magnetic resonance imaging (dMRI) offer quantitative approaches to study skeletal muscle microstructure and architecture. Despite its prevalence in applications for musculoskeletal research, clinical adoption is hindered by a lack of understanding regarding its sensitivity to clinically important biomarkers such as muscle fiber cross-sectional area. This review aims to elucidate how dMRI has been utilized to study skeletal muscle, covering fundamentals of muscle physiology, dMRI acquisition techniques, dMRI modeling, and applications where dMRI has been leveraged to noninvasively study skeletal muscle changes in response to disease, aging, injury, and human performance. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Emerging evidence indicates that incarcerated populations' perceptions of dehumanization by officers are prevalent, yet measures of it are few, and to our knowledge, no self-report measure of dehumanization from officers exists. To fill this gap, we have developed the Perceived Dehumanization from Officers Scale (PDOS), which is designed as a brief measure to assess perception of officer treatment as dehumanizing., Methods: In this article, we provide preliminary evidence from two studies examining the reliability and validity of the PDOS. In study 1, a jail sample (n = 411), we analyzed the exploratory factor structure, internal consistency, and discriminant validity (in relation to procedural justice [PJ]) of the PDOS. Additionally, using a cross-sectional ordinary least squares (OLS) regression analysis, we related independent variables with the PDOS, the dependent variable. In Study 2, a prison sample (n = 2993), we confirmed the findings from study 1., Results: The PDOS appears to be a psychometrically sound measure of perceived dehumanization from officers with strong association between perceptions of PJ and perceived dehumanization from officers., Conclusions: The PDOS provides opportunity for future research, intervention through rehumanization efforts, and signals the important officer treatment. Importantly We close by discussing implications of these studies, limitations, and future research directions to further develop and test the PDOS., (© 2024 Wiley Periodicals LLC.)

Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes. We present data for 109 anticancer drug combinations from AstraZeneca's oncology small molecule portfolio screened in 755 pan-cancer cell lines. Combinations were screened in a 7 × 7 concentration matrix, with more than 4 million measurements of sensitivity, producing an exceptionally data-rich resource. We implement a new approach using combination Emax (viability effect) and highest single agent (HSA) to assess combination benefit. We designed a clinical translatability workflow to identify combinations with clearly defined patient populations, rationale for tolerability based on tumor type and combination-specific "emergent" biomarkers, and exposures relevant to clinical doses. We describe three actionable combinations in defined cancer types, confirmed in vitro and in vivo, with a focus on hematologic cancers and apoptotic targets., Significance: We present the largest cancer drug combination screen published to date with 7 × 7 concentration response matrices for 109 combinations in more than 750 cell lines, complemented by multi-omics predictors of response and identification of "emergent" combination biomarkers. We prioritize hits to optimize clinical translatability, and experimentally validate novel combination hypotheses. This article is featured in Selected Articles from This Issue, p. 695., (©2024 The Authors; Published by the American Association for Cancer Research.)

The medial entorhinal cortex (MEC) is hypothesized to function as a cognitive map for memory-guided navigation. How this map develops during learning and influences memory remains unclear. By imaging MEC calcium dynamics while mice successfully learned a novel virtual environment over ten days, we discovered that the dynamics gradually became more spatially consistent and then stabilized. Additionally, grid cells in the MEC not only exhibited improved spatial tuning consistency, but also maintained stable phase relationships, suggesting a network mechanism involving synaptic plasticity and rigid recurrent connectivity to shape grid cell activity during learning. Increased c-Fos expression in the MEC in novel environments further supports the induction of synaptic plasticity. Unsuccessful learning lacked these activity features, indicating that a consistent map is specific for effective spatial memory. Finally, optogenetically disrupting spatial consistency of the map impaired memory-guided navigation in a well-learned environment. Thus, we demonstrate that the establishment of a spatially consistent MEC map across learning both correlates with, and is necessary for, successful spatial memory., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)