Search

Over the last few years, both ALMA and Spitzer/IRAC observations have revealed a population of likely massive galaxies at $z>3$ that was too faint to be detected in HST rest-frame ultraviolet imaging. However, due to the very limited photometry for individual galaxies, the true nature of these so-called HST-dark galaxies has remained elusive. Here, we present the first sample of such galaxies observed with very deep, high-resolution NIRCam imaging from the Early Release Science Program CEERS. 30 HST-dark sources are selected based on their red colours across 1.6 $μ$m to 4.4 $μ$m. Their physical properties are derived from 12-band multi-wavelength photometry, including ancillary HST imaging. We find that these galaxies are generally heavily dust-obscured ($A_{V}\sim2$ mag), massive ($\log (M/M_{\odot}) \sim10$), star-forming sources at $z\sim2-8$ with an observed surface density of $\sim0.8$ arcmin$^{-2}$. This suggests that an important fraction of massive galaxies may have been missing from our cosmic census at $z>3$ all the way into the Reionization epoch. The HST-dark sources lie on the main sequence of galaxies and add an obscured star formation rate density (SFRD) of $\mathrm{3.2^{+1.8}_{-1.3} \times 10^{-3} M_{\odot}/yr/Mpc^{3}}$ at $z\sim7$ showing likely presence of dust in the Epoch of Reionization. Our analysis shows the unique power of JWST to reveal this previously missing galaxy population and to provide a more complete census of galaxies at $z=2-8$ based on rest-frame optical imaging., 9 pages, 7 figures, accepted to MNRAS

We reduce and analyse the available James Webb Space Telescope (JWST) ERO and ERS NIRCam imaging (SMACS0723, GLASS, CEERS) in combination with the latest deep ground-based near-infrared imaging in the COSMOS field (provided by UltraVISTA DR5) to produce a new measurement of the evolving galaxy UV luminosity function (LF) over the redshift range $z = 8 - 15$. This yields a new estimate of the evolution of UV luminosity density ($\rho_{\rm UV}$), and hence cosmic star-formation rate density ($\rho_{\rm SFR}$) out to within $< 300$\, Myr of the Big Bang. Our results confirm that the high-redshift LF is best described by a double power-law (rather than a Schechter) function up to $z\sim10$, and that the LF and the resulting derived $\rho_{\rm UV}$ (and thus $\rho_{\rm SFR}$), continues to decline gradually and steadily up to $z\sim15$ (as anticipated from previous studies which analysed the pre-existing data in a consistent manner to this study). We provide details of the 61 high-redshift galaxy candidates, 47 of which are new, that have enabled this new analysis. Our sample contains 6 galaxies at $z \ge 12$, one of which appears to set a new redshift record as an apparently robust galaxy candidate at $z \simeq 16.4$, the properties of which we therefore consider in detail. The advances presented here emphasize the importance of achieving high dynamic range in studies of early galaxy evolution, and re-affirm the enormous potential of forthcoming larger JWST programmes to transform our understanding of the young Universe., Comment: 28 pages, 4 figures in main manuscript, accepted for publication in MNRAS. Updated zero-point corrections noted in Appendix C

We utilise JWST NIRCam medium-band imaging to search for extreme redshift ($z \geq 9.5$) galaxy candidates in the Hubble Ultra Deep Field (HUDF) and the additional pointing within the GOODS-South field provided by the second NIRCam module. Our search reveals 6 robust candidates, 3 of which have recently been spectroscopically confirmed. One of these 3 is the previously controversial $z \simeq 12$ galaxy candidate UDF-22980 which is now detected in five JWST NIRCam medium-band filters (F182M, F210M, F430M, F460M and F480M), efficiently excluding alternative low-redshift solutions and allowing us to now report a secure photometric redshift of $z = 11.6 \pm 0.2$. We also detect 2 galaxies at $z \geq 12.5$ including a newly-detected candidate in the imaging provided by the second NIRCam module (south-west of the HUDF) at $z = 12.6 \pm 0.6$. We determine the physical properties of the 6 galaxies by fitting the 14-band photometry with Bagpipes. We find stellar masses of $\log(M_{\star}/{\rm {M_{\odot}}}) \simeq 7.5 - 8.7$ and star-formation rates of $\log(\rm{SFR}/M_{\odot}^{-1} \rm{yr}^{-1}) \simeq 0.3 - 5.0$. Despite the relatively small cosmological volume covered by the HUDF itself and the second NIRCam module imaging, we find that the existence of these galaxies is fully consistent with the latest measurements of both the UV luminosity function and cosmic star-formation rate density at $z\simeq11$, supporting a gradual steady decline in the cosmic star-formation rate density out to at least $z\simeq15$., 8 pages, 4 figures, accepted for publication in MNRAS

Before the end of the Epoch of Reionization, the Hydrogen in the Universe was predominantly neutral. This leads to a strong attenuation of Ly α lines of z ≳ 6 galaxies in the intergalactic medium. Nevertheless, Ly α has been detected up to very high redshifts (z ∼ 9) for several especially UV luminous galaxies. Here, we test to what extent the galaxy’s local environment might impact the Ly α transmission of such sources. We present an analysis of dedicated Hubble Space Telescope (HST) imaging in the CANDELS/EGS field to search for fainter neighbours around three of the most UV luminous and most distant spectroscopically confirmed Ly α emitters: EGS-zs8-1, EGS-zs8-2, and EGSY-z8p7 at zspec = 7.73, 7.48, and 8.68, respectively. We combine the multiwavelength HST imaging with Spitzer data to reliably select z ∼ 7–9 galaxies around the central, UV-luminous sources. In all cases, we find a clear enhancement of neighbouring galaxies compared to the expected number in a blank field (by a factor ∼3–9×). Our analysis thus reveals ubiquitous overdensities around luminous Ly α emitting sources in the heart of the cosmic reionization epoch. We show that our results are in excellent agreement with expectations from the DRAGONS simulation, confirming the theoretical prediction that the first ionized bubbles preferentially formed in overdense regions. While three UV luminous galaxies already have spectroscopic redshifts, the majority of the remaining fainter, surrounding sources are yet to be confirmed via spectroscopy. JWST follow-up observations of the neighbouring galaxies identified here will thus be needed to confirm their physical association and to map out the ionized regions produced by these sources.

Objectives Defects in human cognition commonly result in clinical reasoning failures that can lead to diagnostic errors. Case presentation A 43-year-old female was brought to the emergency department with 4–5 days of confusion, disequilibrium resulting in several falls, and hallucinations. Further investigation revealed tachycardia, diaphoresis, mydriatic pupils, incomprehensible speech and she was seen picking at the air. Given multiple recent medication changes, there was initial concern for serotonin syndrome vs. an anticholinergic toxidrome. She then developed a fever, marked leukocytosis, and worsening encephalopathy. She underwent lumbar puncture and aspiration of an identified left ankle effusion. Methicillin sensitive staph aureus (MSSA) grew from blood, joint, and cerebrospinal fluid cultures within 18 h. She improved with antibiotics and incision, drainage, and washout of her ankle by orthopedic surgery. Conclusions Through integrated commentary on the diagnostic reasoning process from clinical reasoning experts, this case underscores how multiple cognitive biases can cascade sequentially, skewing clinical reasoning toward erroneous conclusions and driving potentially inappropriate testing and treatment. A fishbone diagram is provided to visually demonstrate the major factors that contributed to the diagnostic error. A case discussant describes the importance of structured reflection, a tool to promote metacognitive analysis, and the application of knowledge organization tools such as illness scripts to navigate these cognitive biases.

Southwest Pacific nations are among some of the worst impacted and most vulnerable globally in terms of tropical cyclone (TC)-induced flooding and accompanying risks. This study objectively quantifies the fractional contribution of TCs to extreme rainfall (hereafter, TC contributions) in the context of climate variability and change. We show that TC contributions to extreme rainfall are substantially enhanced during active phases of the Madden–Julian Oscillation and by El Niño conditions (particularly over the eastern southwest Pacific region); this enhancement is primarily attributed to increased TC activity during these event periods. There are also indications of increasing intensities of TC-induced extreme rainfall events over the past few decades. A key part of this work involves development of sophisticated Bayesian regression models for individual island nations in order to better understand the synergistic relationships between TC-induced extreme rainfall and combinations of various climatic drivers that modulate the relationship. Such models are found to be very useful for not only assessing probabilities of TC- and non-TC induced extreme rainfall events but also evaluating probabilities of extreme rainfall for cases with different underlying climatic conditions. For example, TC-induced extreme rainfall probability over Samoa can vary from ~ 95 to ~ 75% during a La Niña period, if it coincides with an active or inactive phase of the MJO, and can be reduced to ~ 30% during a combination of El Niño period and inactive phase of the MJO. Several other such cases have been assessed for different island nations, providing information that have potentially important implications for planning and preparing for TC risks in vulnerable Pacific Island nations.

The southwest Pacific (SWP) region is vulnerable to tropical cyclone (TC) related impacts which adversely affect people, infrastructure and economies across several nations and territories. Skilful TC outlooks are needed for this region, but the erratic nature of SWP TCs and the complex ocean–atmosphere interactions that influence TC behaviour on seasonal timescales presents significant challenges. Here, we present a new TC outlook tool for the SWP using multivariate Poisson regression with indices of multiple climate modes. This approach provides skilful, island-scale TC count outlooks from July (four months ahead of the official TC season start in November). Monthly island-scale TC frequency outlooks are generated between July and December, enabling continuous refinement of predicted TC counts before and during a TC season. Use of this approach in conjunction with other seasonal climate guidance (including dynamical models) has implications for preparations ahead of severe weather events, resilience and risk reduction.

Clinical reasoning encompasses the process of data collection, synthesis, and interpretation to generate a working diagnosis and make management decisions. Situated cognition theory suggests that knowledge is relative to contextual factors, and clinical reasoning in urgent situations is framed by pressure of consequential, time-sensitive decision-making for diagnosis and management. These unique aspects of urgent clinical care may limit the effectiveness of traditional tools to assess, teach, and remediate clinical reasoning.Using two validated frameworks, a multidisciplinary group of clinicians trained to remediate clinical reasoning and with experience in urgent clinical care encounters designed the novel Rapid Evaluation Assessment of Clinical Reasoning Tool (REACT). REACT is a behaviorally anchored assessment tool scoring five domains used to provide formative feedback to learners evaluating patients during urgent clinical situations. A pilot study was performed to assess fourth-year medical students during simulated urgent clinical scenarios. Learners were scored using REACT by a separate, multidisciplinary group of clinician educators with no additional training in the clinical reasoning process. REACT scores were analyzed for internal consistency across raters and observations.Overall internal consistency for the 41 patient simulations as measured by Cronbach's alpha was 0.86. A weighted kappa statistic was used to assess the overall score inter-rater reliability. Moderate reliability was observed at 0.56.To our knowledge, REACT is the first tool designed specifically for formative assessment of a learner's clinical reasoning performance during simulated urgent clinical situations. With evidence of reliability and content validity, this tool guides feedback to learners during high-risk urgent clinical scenarios, with the goal of reducing diagnostic and management errors to limit patient harm.

Background There is a wide chasm in access to essential and emergency surgery between high and low/middle income countries (LMICs). Surgeons worldwide are integral to solutions needed to address this imbalance. Involving surgical trainees, who represent the future of surgery, is vital to this endeavour. The Association of Surgeons in Training (ASiT) is an independent charity that support surgical trainees of all ten surgical specialties in the UK and Ireland. ASiT convened a consensus meeting at the ASiT conference in Liverpool 2016 to discuss trainee engagement with global surgery, including potential barriers and solutions. Methods A face-to-face consensus meeting reviewed the engagement of, and roles for, surgical trainees in global surgery at the ASiT Conference (Liverpool, England), March 2016. Participants self-identified based on experience and interest in the field, and included trainees (residents and students) and consultants (attending grade). Following expert review, seven pre-determined core areas were presented for review and debate. Extensive discussion was facilitated by a consultant and a senior surgical trainee, with expertise in global surgery. The draft derived from these initial discussions was circulated to all those who had participated, and an iterative process of revision was undertaken until a final consensus and recommendations were reached. Results There is increasing interest from trainee surgeons to work in LMICs. There are however, ethical considerations, and it is important that trainees working in LMICs undertake work appropriate to their training stage and competencies. Visiting surgeons must consider the requirements of the hosting centres rather than just their own objectives. If appropriately organised, both short and long-term visits, can enable development of transferable clinical, organisational, research and education skills. A central repository of information on global surgery would be useful to trainees, to complement existing resources. Challenges to trainees considering a global surgery placement include approval for placements while on a training program, financial cost and dangers inherent in working in a resource poor setting. Currently global surgery experience is generally as an out of program experience and does not count for certificate of completion of training (CCT). Methods to recognise surgical trainee global surgery experience as an integrated part of training should be explored, similar to that seen in other specialties. Conclusion There is a role for surgical trainees to become involved in Global Surgery, especially in partnership with local surgeons and with appropriate ethical consideration. Trainees develop translational skills in resource poor settings. Development of appropriate pathways for recognition of global surgery experience for CCT should be considered.

World War I was fought in a period highly charged with both nationalism and religion. Both ideas emerged damaged from the conflict. Nationalism returned in various guises after the conflict, both i...

Posttranscriptional gene regulation by RNA-binding proteins, such as HuR (elavl1), fine-tune gene expression in T cells, leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3′ untranslated region adenylate and uridylate–rich elements. It was previously demonstrated that HuR facilitates Th2 cytokine expression by mRNA stabilization. However, its effects upon IL-2 homeostasis and CD4+ Th2 differentiation are not as well understood. We found that optimal translation of Il2ra (CD25) required interaction of its mRNA with HuR. Conditional HuR knockout in CD4+ T cells resulted in loss of IL-2 homeostasis and defects in JAK–STAT signaling, Th2 differentiation, and cytokine production. HuR-knockout CD4+ T cells from OVA-immunized mice also failed to proliferate in response to Ag. These results demonstrate that HuR plays a pivotal role in maintaining normal IL-2 homeostasis and initiating CD4+ Th2 differentiation.

Tropical cyclones (TCs) pose a significant risk to the nations and territories of the southwest Pacific (SWP). The spatio-temporal variability of TCs makes it challenging to forecast where and when a TC is likely to develop. Therefore, the aim of this study is to better understand the link between large-scale climatic variability, the environmental conditions required for tropical cyclogenesis (TC genesis), and the spatial variability of TC activity. Three modes of climate variability are investigated: (1) El Nino/Southern Oscillation (ENSO), (2) ENSO Modoki, and (3) the Interdecadal Pacific Oscillation (IPO); along with TC genesis parameters: sea surface temperature; 700 hPa relative humidity; 700 hPa vorticity; and vertical wind shear (difference between 200 hPa and 850 hPa winds). Our findings reaffirm the well-established northeast/southwest modulation of TC activity according to El Nino (EN)/La Nina (LN) using an extended TC dataset (1945–2011). In addition, new insights into how ENSO Modoki and the IPO modulate TC activity according to phase and season are identified. Importantly, we show that depending on phase, the IPO can enhance or alter the spatial modulation of TC genesis during ENSO/ENSO Modoki events, in favour of the northeast/southwest modulations typical of IPO positive/negative events. This is particularly the case during the latter half of the SWP TC season. For example, EN events that occur within IPO positive (negative) epochs result in a shift of TC activity up to 1087 km (1288 km) further east (west) during February to April, compared to the typical location of TC activity during EN events. Importantly, these statistical relationships are also associated with anomalously favourable genesis parameters, providing some insights into the physical mechanisms behind the modulations. The findings of this study provide baseline metrics with which to compare climate model simulations and may also facilitate improved seasonal outlooks and better quantification of TC-related risks for the vulnerable island nations and territories of the SWP.

Background Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. Methods LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). Results 1568 participants were randomised during 2007–2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75–1.95) or 0.82 (95% CI 0.52–1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. Conclusions Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening., While low-dose CT is now preferred for lung cancer screening, our randomised trial of smokers with COPD showed that a proposed sequential policy using sputum testing to select who receives low-dose CT and autofluorescence bronchoscopy was ineffective http://bit.ly/2JZujnx

Introduction The US Department of Defense (DoD) has adopted a model concept of the warrior athlete. Identifying latent disease that could compromise the military operator is critical to the warrior athlete concept. Cardiovascular complaints are the important problem recognized in service members evacuated from combat zones, and the incidence of sudden cardiac death in U.S. military recruits is comparable to or greater than that among National Collegiate Athletic Association Athletes. Nevertheless, the mandatory electrocardiogram (ECG) was removed from official U.S. military accession screening policy in 2002. Inclusion of ECG screening in high risk athletics is increasingly recognized as appropriate by professional organizations such as the American Heart Association and American Medical Society for Sports Medicine, though neither recommends ECG for generalized screening in large, low-risk populations. Materials and Methods The appropriate DoD instructions were reviewed in the context of recent literature regarding the sensitivity and specificity of ECG screening for prevention of sudden cardiac arrest or debilitating arrhythmias. Results Challenges to implementation of ECG as a screening modality in U.S. military accessions include clinician interpretation validity and reliability. Modern interpretation criteria and new interpretation technology each serve to mitigate these recognized limitations. Outside experience with implementation of modern ECG suggest potential benefits are significant in the highest risk military groups. Conclusion Prospective study of ECG screening is needed to determine the impact on cardiovascular outcomes in U.S. military populations.

Recent efforts to understand tropical cyclone (TC) activity in the southwest Pacific (SWP) have led to the development of numerous TC databases. The methods used to compile each database vary and are based on data from different meteorological centres, standalone TC databases and archived synoptic charts. Therefore the aims of this study are to (i) provide a spatio-temporal comparison of three TC best-track (BT) databases and explore any differences between them (and any associated implications) and (ii) investigate whether there are any spatial, temporal or statistical differences between pre-satellite (1945–1969), post-satellite (1970–2011) and post-geostationary satellite (1982–2011) era TC data given the changing observational technologies with time. To achieve this, we compare three best-track TC databases for the SWP region (0–35° S, 135° E–120° W) from 1945 to 2011: the Joint Typhoon Warning Center (JTWC), the International Best Track Archive for Climate Stewardship (IBTrACS) and the Southwest Pacific Enhanced Archive of Tropical Cyclones (SPEArTC). The results of this study suggest that SPEArTC is the most complete repository of TCs for the SWP region. In particular, we show that the SPEArTC database includes a number of additional TCs, not included in either the JTWC or IBTrACS database. These SPEArTC events do occur under environmental conditions conducive to tropical cyclogenesis (TC genesis), including anomalously negative 700 hPa vorticity (VORT), anomalously negative vertical shear of zonal winds (VSZW), anomalously negative 700 hPa geopotential height (GPH), cyclonic (absolute) 700 hPa winds and low values of absolute vertical wind shear (EVWS). Further, while changes in observational technologies from 1945 have undoubtedly improved our ability to detect and monitor TCs, we show that the number of TCs detected prior to the satellite era (1945–1969) are not statistically different to those in the post-satellite era (post-1970). Although data from pre-satellite and pre-geostationary satellite periods are currently inadequate for investigating TC intensity, this study suggests that SPEArTC data (from 1945) may be used to investigate long-term variability of TC counts and TC genesis locations.

The destruction caused by tropical cyclone (TC) Pam in March 2015 is considered one of the worst natural disasters in the history of Vanuatu. It has highlighted the need for a better understanding of TC impacts and adaptation in the Southwest Pacific (SWP) region. Therefore, the key aims of this study are to (i) understand local perceptions of TC activity, (ii) investigate impacts of TC activity and (iii) uncover adaptation strategies used to offset the impacts of TCs. To address these aims, a survey (with 130 participants from urban areas) was conducted across three SWP small island states (SISs): Fiji, Vanuatu and Tonga (FVT). It was found that respondents generally had a high level of risk perception and awareness of TCs and the associated physical impacts, but lacked an understanding of the underlying weather conditions. Responses highlighted that current methods of adaptation generally occur at the local level, immediately prior to a TC event (preparation of property, gathering of food, finding a safe place to shelter). However higher level adaptation measures (such as the modification to building structures) may reduce vulnerability further. Finally, we discuss the potential of utilising weather-related traditional knowledge and non-traditional knowledge of empirical and climate-model-based weather forecasts to improve TC outlooks, which would ultimately reduce vulnerability and increase adaptive capacity. Importantly, lessons learned from this study may result in the modification and/or development of existing adaptation strategies.

Posttranscriptional gene regulation by RNA-binding proteins, such as HuR (elavl1), fine-tune gene expression in T cells, leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3′ untranslated region adenylate and uridylate–rich elements. It was previously demonstrated that HuR facilitates Th2 cytokine expression by mRNA stabilization. However, its effects upon IL-2 homeostasis and CD4+ Th2 differentiation are not as well understood. We found that optimal translation of Il2ra (CD25) required interaction of its mRNA with HuR. Conditional HuR knockout in CD4+ T cells resulted in loss of IL-2 homeostasis and defects in JAK–STAT signaling, Th2 differentiation, and cytokine production. HuR-knockout CD4+ T cells from OVA-immunized mice also failed to proliferate in response to Ag. These results demonstrate that HuR plays a pivotal role in maintaining normal IL-2 homeostasis and initiating CD4+ Th2 differentiation.

Extracted from text ... Introduction Rectal prolapse is commonly seen at the extremes of age groups. In adults, it is almost exclusively seen in females. The aetiology of rectal prolapse in adult males is not completely understood. A case of rectal prolapse in a young adult male patient is presented and a likely unique aetiopathology is discussed. Case history A 39-year-old male Caucasian patient presented with a history of rectal bleeding and faecal incontinence. The patient was previously healthy and had no relevant past medical or surgical history. Specifically, there was no history of constipation, straining, chronic cough, psychiatric illness, rectal or pelvic trauma, ..

Highlight This work investigated the relationship between cell-wall properties in diverse maize lines that contribute to the differences in enzymatic hydrolysis yields for both untreated and mild NaOH-pre-treated biomass., A maize (Zea mays L. subsp. mays) diversity panel consisting of 26 maize lines exhibiting a wide range of cell-wall properties and responses to hydrolysis by cellulolytic enzymes was employed to investigate the relationship between cell-wall properties, cell-wall responses to mild NaOH pre-treatment, and enzymatic hydrolysis yields. Enzymatic hydrolysis of the cellulose in the untreated maize was found to be positively correlated with the water retention value, which is a measure of cell-wall susceptibility to swelling. It was also positively correlated with the lignin syringyl/guaiacyl ratio and negatively correlated with the initial cell-wall lignin, xylan, acetate, and p-coumaric acid (pCA) content, as well as pCA released from the cell wall by pre-treatment. The hydrolysis yield following pre-treatment exhibited statistically significant negative correlations to the lignin content after pre-treatment and positive correlations to the solubilized ferulic acid and pCA. Several unanticipated results were observed, including a positive correlation between initial lignin and acetate content, lack of correlation between acetate content and initial xylan content, and negative correlation between each of these three variables to the hydrolysis yields for untreated maize. Another surprising result was that pCA release was negatively correlated with hydrolysis yields for untreated maize and, along with ferulic acid release, was positively correlated with the pre-treated maize hydrolysis yields. This indicates that these properties that may negatively contribute to the recalcitrance in untreated cell walls may positively contribute to their deconstruction by alkaline pre-treatment.

A machine learning approach that we term the `Stochastic Replica Voting Machine' (SRVM) algorithm is presented and applied to a binary and a 3-class classification problems in materials science. Here, we employ SRVM to predict candidate compounds capable of forming stable perovskites and double perovskites and further classify binary ($AB$) solids. The results of our binary and ternary classifications compared well to those obtained by SVM and neural network algorithms., Comment: 45 pages, 25 figures

The posttranscriptional mechanisms by which RNA binding proteins (RBPs) regulate T-cell differentiation and cytokine production in vivo remain unclear. The RBP HuR binds to labile mRNAs, usually leading to increases in mRNA stability and/or translation. Previous work demonstrated that HuR binds to the mRNAs encoding the Th2 transcription factor trans-acting T-cell-specific transcription factor (GATA-3) and Th2 cytokines interleukin (IL)-4 and IL-13, thereby regulating their expression. By using a novel conditional HuR knockout (KO) mouse in which HuR is deleted in activated T cells, we show that Th2-polarized cells from heterozygous HuR conditional (OX40-Cre HuR(fl/+)) KO mice had decreased steady-state levels of Gata3, Il4 and Il13 mRNAs with little changes at the protein level. Surprisingly, Th2-polarized cells from homozygous HuR conditional (OX40-Cre HuR(fl/fl)) KO mice showed increased Il2, Il4 and Il13 mRNA and protein via different mechanisms. Specifically, Il4 was transcriptionally upregulated in HuR KO T cells, whereas Il2 and Il13 mRNA stabilities increased. Additionally, when using the standard ovalbumin model of allergic airway inflammation, HuR conditional KO mice mounted a robust inflammatory response similar to mice with wild-type HuR levels. These results reveal a complex differential posttranscriptional regulation of cytokines by HuR in which gene dosage plays an important role. These findings may have significant implications in allergies and asthma, as well as autoimmune diseases and infection.

Surveys are frequently used to collect data in graduate medical education (GME) settings.1 However, if a GME survey is not rigorously designed, the quality of the results is likely to be lower than desirable. In a recent editorial we introduced a framework for developing survey instruments.1 This systematic approach is intended to improve the quality of GME surveys and increase the likelihood of collecting survey data with evidence of reliability and validity. In this article we illustrate how researchers in medical education may operationalize this framework with examples from a survey we developed during the recent integration of 2 independent internal medicine (IM) residency programs.