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Premise: Rafflesia are rare holoparasitic plants. In the Philippines, all but one species are found only on single islands. This study aimed to better understand the factors contributing to this distributional pattern. Specifically, we sought to determine whether narrow environmental tolerances of host and/or parasite species might explain their island endemicity. Methods: We used Maxent species distribution modeling to identify areas with suitable habitat for R. lagascae, R. lobata, and R. speciosa and their Tetrastigma host species. These analyses were carried out for current climate conditions and two future climate change scenarios. Results: Although species distribution models indicated suitable environmental conditions for the Tetrastigma host species in many parts of the Philippines, considerably fewer areas were inferred to have suitable conditions for the three Rafflesia species. Some of these areas are on islands from which they have not been reported. All three species will face significant threats as a result of climate change. Conclusions: Our results suggest that limited inter‐island dispersibility and/or specific environmental requirements are likely responsible for the current pattern of island endemicity of the three Rafflesia species, rather than environmental requirements of their Tetrastigma host species. [ABSTRACT FROM AUTHOR]

Background: Allergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal‐resident memory CD8+ T (TRM) cells play a key role. The mechanisms involved in the activation of CD8+ TRM cells during allergic flare‐up responses are not understood. Methods: The expression of CD100 and its ligand Plexin B2 on CD8+ TRM cells and keratinocytes before and after allergen exposure was determined by flow cytometry and RT‐qPCR. The role of CD100 in the inflammatory response during the challenge phase of ACD was determined in a model of ACD in CD100 knockout and wild‐type mice. Results: We show that CD8+ TRM cells express CD100 during homeostatic conditions and up‐regulate it following re‐exposure of allergen‐experienced skin to the experimental contact allergen 1‐fluoro‐2,4‐dinitrobenzene (DNFB). Furthermore, Plexin B2 is up‐regulated on keratinocytes following exposure to some contact allergens. We show that loss of CD100 results in a reduced inflammatory response to DNFB with impaired production of IFNγ, IL‐17A, CXCL1, CXCL2, CXCL5, and IL‐1β and decreased recruitment of neutrophils to the epidermis. Conclusion: Our study demonstrates that CD100 is expressed on CD8+ TRM cells and is required for full activation of CD8+ TRM cells and the flare‐up response of ACD. [ABSTRACT FROM AUTHOR]

Background: The junctional adhesion molecule‐like protein (JAML) plays important roles in wound healing and activation of epidermal γδ T cells in mice. Whether JAML plays a role in contact hypersensitivity (CHS), the animal model of allergic contact dermatitis (ACD), is not known. Methods: To examine the role of JAML in CHS, we used various mouse models of CHS in JAML knockout (KO) and wild‐type (WT) mice. Furthermore, the expression of the JAML ligand coxsackievirus and adenovirus receptor (CXADR) on keratinocytes was accessed in vitro and in vivo. Results: JAML KO mice had a diminished inflammatory response during both the sensitization and elicitation phase of CHS and had reduced numbers of CD8+ and CD4+ T cells in the epidermis. Furthermore, interferon γ (IFNγ), interleukin 1β (IL‐1β) and CXCL10 production were significantly reduced in JAML KO mice during the elicitation phase. We found that CD8+ T cells express JAML and that JAML is essential for rapid flare‐up responses to contact allergens. Finally, we show that keratinocytes up‐regulate the JAML ligand CXADR following exposure to contact allergens. Conclusion: Our study is the first to show a central role of JAML in CHS and reveals a potential new target for the treatment of ACD in humans. [ABSTRACT FROM AUTHOR]

We recently developed a rat whole exome sequencing (WES) panel and used it to evaluate early somatic mutations in archival liver tissues from F344/N rats exposed to the hepatocarcinogen, Aflatoxin B1 (AFB1), a widely studied, potent mutagen and hepatocarcinogen associated with hepatocellular carcinoma (HCC). Rats were exposed to 1‐ppm AFB1 in feed for 14, 90, and 90 days plus a recovery 60‐day, non‐exposure period (150‐day) timepoint. Isolated liver DNA was exome sequenced. We identified 172 sequence variants across all timepoints, of which 101 were non‐synonymous variants. Well‐annotated genes carried a diverse set of 29 non‐synonymous mutations at 14 days, increasing to 39 mutations at 90 days and then decreasing to 33 mutations following the 60‐day recovery. Gene Set Enrichment Analysis conducted on previously reported, available RNA expression data of the same exome sequenced archival samples identified altered transcripts in pathways associated with malignant transformation. These included HALLMARK gene sets associated with cell proliferation (MYC Targets Version 1 and Version 2, E2F targets), cell cycle (G2M checkpoint, mitotic spindle), cell death (apoptosis), and DNA damage (DNA repair, UV response Up, Reactive oxygen species) pathways. DriverNet Impact analysis integrated exome‐seq and expression data to reveal somatic mutations in Mcm8, Bdp1, and Cct6a that may drive cancer formation. Connectivity with transcript expression changes identified these genes as the top‐ranked candidate driver genes associated with hepatocellular transformation. In conclusion, exome sequencing revealed early somatic mutations that may play a role in cancer cell transformation that are translatable to aflatoxin‐induced HCC. Whole exome sequencing revealed early somatic mutations that may play a role in cancer cell transformation that are translatable to aflatoxin‐induced HCC. Integration of exome‐sequencing with transcript expression changes identified Mcm8, Bdp1, and Cct6a as the top‐ranked candidate driver genes associated with hepatocellular transformation following short term (14‐day) and sub‐chronic (90‐day) AFB1 exposure. [ABSTRACT FROM AUTHOR]

This paper examines the empirical relationship between the Madden–Julian oscillation (MJO), the quasi‐biennial oscillation (QBO), and atmospheric river (AR) activity and precipitation in California on subseasonal time scales. We introduce an experimental forecast tool that uses observed anomaly patterns during a 38 yr period to predict the probability of above‐ and below‐normal AR activity and precipitation at lead times of 1–6 weeks based on the phase and amplitude of the MJO and QBO. The hindcast prediction skill of probabilistic AR activity and precipitation forecasts is evaluated for Northern, Central, and Southern California, as well as two sets of smaller geographical domains. These smaller domains are more relevant for water resource management and allow us to investigate the sensitivity of prediction skill to domain size. Consistent with previous studies, our results demonstrate that subseasonal AR activity and precipitation in California are strongly modulated by the MJO and QBO. The anomaly patterns of AR activity and precipitation vary considerably throughout the cool season, with a tendency toward below‐normal AR activity and precipitation during easterly QBO and above‐normal AR activity and precipitation during westerly QBO in JFM. The opposite patterns are generally observed in OND, but the anomaly signals are weaker and less coherent for AR activity. Certain combinations of MJO phase, QBO phase, lag time, and season yield notably higher skill scores, reinforcing the notion of "windows of opportunity" for skillful subseasonal‐to‐seasonal predictions. In California, these forecasts of opportunity are predominantly associated with easterly QBO in JFM and FMA. Plain Language Summary: This paper examines the relationship between the Madden–Julian oscillation (MJO), the quasi‐biennial oscillation (QBO), and atmospheric river (AR) activity and precipitation in California. We introduce an experimental forecast tool that shows the likelihood of above‐normal and below‐normal AR activity and precipitation based on the phases of the MJO and QBO. Consistent with previous studies, our results demonstrate that AR activity and precipitation in California are strongly influenced by the MJO and the QBO. There is a tendency for below‐normal AR activity and precipitation during easterly QBO conditions in January–March. The opposite pattern (above‐normal AR activity and precipitation) generally occurs during westerly QBO conditions. The results also suggest that our forecast tool has some potential to improve the prediction of AR activity and precipitation. The reliability and usefulness of this forecast tool depend on multiple factors, including the MJO phase, the QBO phase, and the time of year. In California, this forecast tool is likely to provide the most beneficial value during easterly QBO conditions in mid‐winter through early spring. Key Points: The modulation of atmospheric river (AR) activity and precipitation in California by the Madden‐Julian oscillation and quasi‐biennial oscillation is quantifiedA hindcast skill assessment of probabilistic AR activity and precipitation forecasts is presentedAn experimental subseasonal AR activity and precipitation forecast tool is introduced [ABSTRACT FROM AUTHOR]

Summary: Despite the paramount role of plant diversity for ecosystem functioning, biogeochemical cycles, and human welfare, knowledge of its global distribution is still incomplete, hampering basic research and biodiversity conservation.Here, we used machine learning (random forests, extreme gradient boosting, and neural networks) and conventional statistical methods (generalized linear models and generalized additive models) to test environment‐related hypotheses of broad‐scale vascular plant diversity gradients and to model and predict species richness and phylogenetic richness worldwide. To this end, we used 830 regional plant inventories including c. 300 000 species and predictors of past and present environmental conditions.Machine learning showed a superior performance, explaining up to 80.9% of species richness and 83.3% of phylogenetic richness, illustrating the great potential of such techniques for disentangling complex and interacting associations between the environment and plant diversity. Current climate and environmental heterogeneity emerged as the primary drivers, while past environmental conditions left only small but detectable imprints on plant diversity.Finally, we combined predictions from multiple modeling techniques (ensemble predictions) to reveal global patterns and centers of plant diversity at multiple resolutions down to 7774 km2. Our predictive maps provide accurate estimates of global plant diversity available at grain sizes relevant for conservation and macroecology. See also the Commentary on this article by Puglielli & Pärtel, 237: 1074–1077. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Inflammatory bowel disease (IBD) activity during pregnancy is associated with adverse pregnancy outcomes. We aimed to identify key clinical characteristics that predict disease activity during pregnancy. Methods: Between January 2008 through 2021, we identified all singleton pregnancies among women with IBD recorded in patient and birth registries at a tertiary IBD centre in Denmark. Maternal and infant data were retrieved from medical records. Demographics, Physicians Global Assessment (PGA) of disease activity 6 months prior to pregnancy and in all three trimesters of pregnancy and pregnancy outcomes were recorded. Results: In 609 pregnancies, we observed 603 (99.0%) live births. Disease activity in one or more trimesters was seen in 283 women (46.5%). UC phenotype was associated with an increase in risk of disease activity (adjusted OR = 2.6 [1.8–3.9]; p < 0.001). Disease activity within 6 months prior to conceiving (169 women [27.7%]) was associated with an increased risk of continuous disease activity during pregnancy (adjusted OR of 5.3 [3.5–8.2]; p < 0.001). Disease activity during a previous pregnancy was associated with an increased risk of flares in subsequent pregnancies (adjusted OR of 3.2 [1.5–6.6]; p = 0.002). Sustained clinical remission throughout pregnancy was associated with an increased probability of normal birth term, birthweight and low risk of fetal growth restriction (FGR) and stillbirth. Conclusion: Predictors for disease activity include disease activity in a previous pregnancy and/or prior to conception, as well as UC phenotype. Reassuringly, women with IBD in remission are not at increased risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Allergic contact dermatitis (ACD) is classically described as a delayed‐type hypersensitivity reaction. However, patients often experience flare‐ups characterized by itching erythema, edema, and often vesicles occurring within hours after re‐exposure of previously sensitized skin to the specific contact allergen. Recent studies have indicated that skin‐resident memory T (TRM) cells play a central role in ACD. However, the pathogenic role of TRM cells in allergen‐induced flare‐ups is not known. Methods: By the use of various mouse models and cell depletion protocols, we investigated the role of epidermal TRM cells in flare‐up reactions to the experimental contact allergen 1‐fluoro‐2,4‐dinitrobenzene. The inflammatory response was measured by changes in ear thickness, and the cellular composition in epidermis was determined by flow cytometry and confocal microscopy. Finally, adaptive transfer and inhibitors were used to determine the role of TRM cells, neutrophils, and CXCL1/CXCL2 in the response. Results: We show that CD8+ TRM cells initiate massive infiltration of neutrophils in the epidermis within 12 h after re‐exposure to the contact allergen. Depletion of neutrophils before re‐exposure to the allergen abrogated the flare‐up reactions. Furthermore, we demonstrate that CD8+ TRM cells mediate neutrophil recruitment by inducing CXCL1 and CXCL2 production in the skin, and that blockage of the C‐X‐C chemokine receptor type 1 and 2 inhibits flare‐up reactions and neutrophil infiltration. Conclusion: As the first, we show that epidermal CD8+ TRM cells cause ACD flare‐ups by rapid recruitment of neutrophils to the epidermis. [ABSTRACT FROM AUTHOR]

Rapid environmental change is reshaping ecosystems and driving species loss globally. Carnivore populations have declined and retracted rapidly and have been the target of numerous translocation projects. Success, however, is complicated when these efforts occur in novel ecosystems. Identifying refuges, locations that are resistant to environmental change, within a translocation framework should improve population recovery and persistence. American martens (Martes americana) are the most frequently translocated carnivore in North America. As elsewhere, martens were extirpated across much of the Great Lakes region by the 1930s and, despite multiple translocations beginning in the 1950s, martens remain of regional conservation concern. Surprisingly, martens were rediscovered in 2014 on the Apostle Islands of Lake Superior after a putative absence of >40 yr. To identify the source of martens to the islands and understand connectivity of the reintroduction network, we collected genetic data on martens from the archipelago and from all regional reintroduction sites. In total, we genotyped 483 individual martens, 43 of which inhabited the Apostle Islands (densities 0.42–1.46 km−2). Coalescent analyses supported the contemporary recolonization of the Apostle Islands with progenitors likely originating from Michigan, which were sourced from Ontario. We also identified movements by a first‐order relative between the Apostle Islands and the recovery network. We detected some regional gene flow, but in an unexpected direction: individuals moving from the islands to the mainland. Our findings suggest that the Apostle Islands were naturally recolonized by progeny of translocated individuals and now act as a source back to the reintroduction sites on the mainland. We suggest that the Apostle Islands, given its protection from disturbance, complex forest structure, and reduced carnivore competition, will act as a potential refuge for marten along their trailing range boundary and a central node for regional recovery. Our work reveals that translocations, even those occurring along southern range boundaries, can create recovery networks that function like natural metapopulations. Identifying refuges, locations that are resistant to environmental change, within these recovery networks can further improve species recovery, even within novel environments. Future translocation planning should a priori identify potential refuges and sources to improve short‐term recovery and long‐term persistence. [ABSTRACT FROM AUTHOR]

Summary: Body mass index (BMI) at child and adolescent ages is positively associated with adult coronary heart disease (CHD) whereas height at these ages may be inversely associated with CHD. However, potential effects of age, sex, and socioeconomic status on associations between BMI and CHD are less investigated. We conducted a systematic review and meta‐analysis of BMI and height at ages 2–19 years in relation to adult CHD and examined effects of age, sex, socioeconomic status, and other factors. Twenty‐two studies on BMI and five on height were included, comprising 5,538,319 individuals and 69,830 CHD events. Random effects meta‐analyses were conducted. Child and adolescent BMI were positively associated with CHD (hazard ratio = 1.12; 95% confidence interval [CI] [1.01, 1.25] per standard deviation [SD]), and categorical analyses supported these findings. The associations did not significantly differ by age, sex, or by adjustment for socioeconomic status. Child and adolescent height were inversely associated with CHD (hazard ratio = 0.87; 95% CI [0.81, 0.93] per SD), and categorical analyses agreed. Insufficient studies on height precluded subgroup analyses. Heterogeneity was generally high in all analyses. We found that BMI in youth is positively associated with adult CHD regardless of sex or adjustment for socioeconomic status whereas height is inversely associated with later risk of CHD. [ABSTRACT FROM AUTHOR]

Cell‐free DNA circulates in plasma at low levels as a normal by‐product of cellular apoptosis. Multiple clinical pathologies, as well as environmental stressors can lead to increased circulating cell‐free DNA (ccfDNA) levels. Plasma DNA studies frequently employ targeted amplicon deep sequencing platforms due to limited concentrations (ng/ml) of ccfDNA in the blood. Here, we report whole genome sequencing (WGS) and read distribution across chromosomes of ccfDNA extracted from two human plasma samples from normal, healthy subjects, representative of limited clinical samples at <1 ml. Amplification was sufficiently robust with ~90% of the reference genome (GRCh38.p2) exhibiting 10X coverage. Chromosome read coverage was uniform and directly proportional to the number of reads for each chromosome across both samples. Almost 99% of the identified genomic sequence variants were known annotated dbSNP variants in the hg38 reference genome. A high prevalence of C>T and T>C mutations was present along with a strong concordance of variants shared between the germline genome databases; gnomAD (81.1%) and the 1000 Genome Project (93.6%). This study demonstrates isolation and amplification procedures from low input ccfDNA samples that can detect sequence variants across the whole genome from amplified human plasma ccfDNA that can translate to multiple clinical research disciplines. [ABSTRACT FROM AUTHOR]

Background: Pituitary pars intermedia dysfunction (PPID) is commonly investigated using plasma ACTH concentrations but problems exist with currently available diagnostic thresholds. Objectives: To derive temporally specific diagnostic thresholds for equine plasma ACTH concentration to be used alongside clinical judgement in each individual week of the year and appropriate for the degree of clinical suspicion in any given case. Furthermore, to apply these thresholds to compare the prevalence of high and low ACTH in two subgroups of animals with high and low clinical suspicion of PPID. Study design: A retrospective population study examining a large laboratory database of equine plasma ACTH concentrations using an indirect approach to calculate diagnostic thresholds. Methods: Logs of plasma ACTH concentrations from 75 892 individual horses were examined using robust L2 estimation of mixtures of two normal distributions in categories of each week and month of the year. Thresholds dividing the two populations of high‐ACTH and low‐ACTH horses were then established at different levels of sensitivity and specificity and compared with clinical subgroups of horses divided based on reported clinical signs, as having high (n = 4036) or low (n = 3022) clinical suspicion of PPID. Results: For most of the year there were small interweek differences in diagnostic thresholds. However, from mid‐June to early‐December diagnostic thresholds showed greater interweek variability, reaching a maximum in late September and early October. Grouping of high‐ and low‐ACTH compared favourably with grouping based on clinical signs. Main limitations: Given the multiple sources of diagnostic samples, pre‐analytical data could not be fully verified. Conclusions: Diagnostic thresholds for equine plasma ACTH vary through the year. It is especially important to consider the temporally specific threshold between June and December. Different clinical thresholds can be used depending on the case circumstances and whether a false‐positive or false‐negative diagnosis is deemed least desirable. [ABSTRACT FROM AUTHOR]

Impairments in visuomotor integration (VMI) may contribute to anomalous development of motor, as well as social‐communicative, skills in children with autism spectrum disorder (ASD). However, it is relatively unknown whether VMI impairments are specific to children with ASD versus children with other neurodevelopmental disorders. As such, this study addressed the hypothesis that children with ASD, but not those in other clinical control groups, would show greater deficits in high‐VMI dynamic grip‐force tracking versus low‐VMI static presentation. Seventy‐nine children, aged 7–17 years, participated: 22 children with ASD, 17 children with fetal alcohol spectrum disorder (FASD), 18 children with Attention‐Deficit Hyperactivity Disorder (ADHD), and 22 typically developing (TD) children. Two grip‐force tracking conditions were examined: (1) a low‐VMI condition (static visual target) and (2) a high‐VMI condition (dynamic visual target). Low‐frequency force oscillations <0.5 Hz during the visuomotor task were also examined. Two‐way ANCOVAs were used to examine group x VMI and group x frequency effects (α = 0.05). Children with ASD showed a difficulty, above that seen in the ADHD/FASD groups, tracking dynamic, but not static, visual stimuli as compared to TD children. Low‐frequency force oscillations <0.25 Hz were also significantly greater in the ASD versus the TD group. This study is the first to report VMI deficits during dynamic versus static grip‐force tracking and increased proportion of force oscillations <0.25 Hz during visuomotor tracking in the ASD versus TD group. Dynamic VMI impairments may be a core psychophysiologic feature that could contribute to impaired development of motor and social‐communicative skills in ASD. Lay Summary Children with autism spectrum disorder (ASD) show difficulties using dynamic visual stimuli to guide their own movements compared to their typically developing (TD) peers. It is unknown whether children without a diagnosis of ASD, but with other neurological disorders, show similar difficulties processing dynamic visual stimuli. In this study, we showed that children with ASD show a difficulty using dynamic, but not static, visual stimuli to guide movement that may explain atypical development of motor and social skills. [ABSTRACT FROM AUTHOR]

Recent high impact wildfires and droughts in California and Nevada have been linked to extremes in the Evaporative Demand Drought Index (EDDI) and Standardized Precipitation Evapotranspiration Index (SPEI), respectively. Both indices are dependent on reference evapotranspiration (ET0). Future changes in ET0 for California and Nevada are examined, calculated from global climate model simulations downscaled by Localized Constructed Analogs (LOCA). ET0 increases of 13–18% at seasonal timescales are projected by late century (2070–2099), with greatest relative increases in winter and spring. Seasonal ET0 increases are most strongly driven by warmer temperatures, with increasing specific humidity having a smaller, but noteworthy, counter tendency. Extreme (95th percentile) EDDI values on the 2‐week timescale have coincided with recent large wildfires in the area. Two‐week EDDI extremes are projected to increase by 6–10 times during summer and 4–6 times during autumn by the end of the century. On multiyear timescales, the occurrence of extreme droughts based on 3‐year SPEI below the historical fifth percentile, similar to that experienced during the 2012–2016 drought across the region, is projected to increase 3–15 times by late century. Positive trends in extreme multiyear droughts will further increase seasonal fire potential through degraded forests and increased fuel loads and flammability. Understanding how these drought metrics change on various climate timescales at the local level can provide fundamental information to support the development of long‐term adaptation strategies for wildland fire and water resource management. Plain Language Summary: Since the start of the 21st century, California and Nevada have observed extreme wildland fires and droughts that have caused devastating impacts to ecosystems and society. A common feature of these events has been very high atmospheric evaporative demand—the "thirst" of the atmosphere—which has largely been driven by increased air temperatures caused by anthropogenic climate change. This study examines projected changes in evaporative demand, which of the input variables are causing those changes and how the frequency of extreme wildfire potential and multiyear droughts will change. Evaporative demand is found to increase during all seasons, and increased temperatures drive most of that change. The likelihood of extreme wildfire potential based on 2‐week periods of elevated evaporative demand during summer and autumn increases substantially. A climatic water balance based on precipitation and evaporative demand indicates extreme 3‐year droughts that hold potential to deplete regional‐scale water supply also become much more likely. Future adaptation planning efforts for wildfire management agencies, forest management, and water resource managers should account for a greater likelihood of more extreme events. Key Points: All climate models show increasing reference evapotranspiration (ET0) through the end of the centuryIncreased air temperature has the greatest contribution to projected ET0 increasesExtreme ET0‐based wildfire potential and 3‐year droughts based on precipitation minus ET0 become much more frequent in the future [ABSTRACT FROM AUTHOR]

Background: Androgens function through DNA and non‐DNA binding‐dependent signalling of the androgen receptor (AR). How androgens promote erythropoiesis is not fully understood. Design and methods: To identify the androgen signalling pathway, we treated male mice lacking the second zinc finger of the DNA‐binding domain of the AR (ARΔZF2) with non‐aromatizable 5α‐dihydrotestosterone (5α‐DHT) or aromatizable testosterone. To distinguish direct hematopoietic and non‐hematopoietic mechanisms, we performed bone marrow reconstitution experiments. Results: In wild‐type mice, 5α‐DHT had greater erythroid activity than testosterone, which can be aromatized to estradiol. The erythroid response in wild‐type mice following 5α‐DHT treatment was associated with increased serum erythropoietin (EPO) and its downstream target erythroferrone, and hepcidin suppression. 5α‐DHT had no erythroid activity in ARΔZF2 mice, proving the importance of DNA binding by the AR. Paradoxically, testosterone, but not 5α‐DHT, suppressed EPO levels in ARΔZF2 mice, suggesting testosterone following aromatization may oppose the erythroid‐stimulating effects of androgens. Female wild‐type mice reconstituted with ARΔZF2 bone marrow cells remained responsive to 5α‐DHT. In contrast, ARΔZF2 mice reconstituted with female wild‐type bone marrow cells showed no response to 5α‐DHT. Conclusion: Erythroid promoting effects of androgens are mediated through DNA binding‐dependent actions of the AR in non‐hematopoietic cells, including stimulating EPO expression. [ABSTRACT FROM AUTHOR]

The Endeavour Segment of the Juan de Fuca Ridge is well known for its abundance of hydrothermal vents and chimneys. One‐meter scale multibeam mapping data collected by an autonomous undersea vehicle revealed 572 chimneys along the central 14 km of the segment, although only 47 are named and known to be active. Hydrothermal deposits are restricted to the axial graben and the near‐rims of the graben above a seismically mapped axial magma lens. The sparse eruptive activity on the segment during the last 4,300 years has not buried inactive chimneys, as occurs at more magmatically robust mid‐ocean ridges. Key Points: The Endeavour Segment of the Juan de Fuca Ridge hosts 572 hydrothermal sulfide chimneys in the central 14 km of the segmentHydrothermal activity is limited to the axial graben and the near rims of the graben above the seismically imaged magma lensThe minimal eruptive activity on Endeavour for the past 4,300 years does not bury inactive chimneys as occurs on other ridges [ABSTRACT FROM AUTHOR]

Background: Responsible use of antimicrobials in equine practice relies on knowledge of common bacterial isolates and their antimicrobial sensitivities. Objectives: To assess the frequency of bacterial resistance to a combination of parenteral penicillin and gentamicin and to trimethoprim and sulfamethoxazole for PO use in a selection of clinical isolates, and subsequently to determine the prevalence of resistance to antimicrobials that might then be used as alternatives to first‐line antimicrobials for the same isolates. Methods: Retrospective analysis of minimal inhibitory concentrations (MICs) of antimicrobials for 6354 bacterial isolates from 365 ambulatory practices and 519 isolates from a referral hospital. The MICs were used to indicate sensitivity or resistance to commonly used antimicrobials and the prevalences of resistance were compared between origin of the isolates, and among antimicrobial drugs. Results: Isolates from the referral hospital were significantly (P <.05) more likely to be resistant to the antimicrobials tested than those derived from ambulatory practice. Overall, 91% of the ambulatory isolates and 64% of the hospital isolates were sensitive to penicillin‐gentamicin. For trimethoprim‐sulfamethoxazole combination, 82% of the ambulatory practice isolates and 56% of the referral hospital isolates were sensitive. Conclusions and Clinical Importance: Most isolates were sensitive to penicillin and gentamicin as well as trimethoprim‐sulfamethoxazole. No predictable efficacious second choice antimicrobial was identified for those isolates resistant to the first‐line antimicrobials. The likelihood of isolates being sensitive to second choice antimicrobials was variable but generally higher for ambulatory isolates compared to referral isolates. Bacterial identification and measurement of MIC are essential to make the appropriate antimicrobial choice. [ABSTRACT FROM AUTHOR]

Abstract: Meter‐scale AUV bathymetric mapping and ROV sampling of the entire 47 km‐long Alarcon Rise between the Pescadero and Tamayo transforms show that the shallowest inflated portion of the segment hosts all four active hydrothermal vent fields and the youngest, hottest, and highest effusion rate lava flows. This shallowest inflated part is located ∼1/3 of the way between the Tamayo and Pescadero transforms and is paved by a 16 km2 channelized flow that erupted from 9 km of en echelon fissures and is larger than historic flows on the East Pacific Rise or on the Gorda and Juan de Fuca Ridges. Starting ∼5 km south of the Pescadero transform, 6.5 km of the Alarcon Rise is characterized by faulted ridges and domes of fractionated lavas ranging from basaltic andesite to rhyolite with up to 77.3 wt % SiO2. These are the first known rhyolites from the submarine global mid‐ocean ridge system. Silicic lavas range from >11.7 ka, to as young as 1.1 ka. A basalt‐to‐basaltic andesite sequence and an andesite‐to‐dacite‐to‐rhyolite sequence are consistent with crystal fractionation but some intermediate basaltic andesite and andesite formed by mixing basalt with dacite or rhyolite. Magmatism occurred along the bounding Tamayo and Pescadero transforms as extensive channelized flows. The flows erupted from ring faults surrounding uplifted sediment hills inferred to overlie sills. The transforms are transtensional to accommodate magma migration from the adjacent Alarcon Rise. [ABSTRACT FROM AUTHOR]

Background Pharmacokinetic data show reduced mycophenolic acid levels in renal transplant recipients taking mycophenolate mofetil ( MMF) and proton pump inhibitors ( PPIs) concomitantly. This reduced exposure could increase rejection risk. The typical initial MMF dose post renal transplantation is 2 g/day, which often requires dose reduction secondary to side effects. Existing studies have not shown significant acute rejection differences for patients taking MMF- PPI versus patients taking MMF-ranitidine. Objective The purpose of this study was to evaluate clinical outcomes in renal transplant recipients receiving a lower MMF dose than previously studied (1.5 g/day) and either a PPI or histamine-2 receptor antagonist (H2 RA). Methods This retrospective cohort study included adult subjects receiving a renal transplant between January 1, 2009, and June 30, 2013. Comparison groups were defined based on acid-suppressing therapy class prescribed at discharge from transplantation. The primary outcome was acute rejection incidence within 1 year posttransplantation. Results Of 728 renal transplant recipients screened, 522 were included: 183 taking a PPI and 339 taking an H2 RA. There was no significant difference in acute rejection within 1 year (H2 RA 19% versus PPI 14%, p=0.12) or 3 months (4% vs 5%, p=0.44, respectively) posttransplantation. Maintenance immunosuppression ( MMF dose and tacrolimus troughs) was similar between groups at 3 months and 1 year. Graft and patient survivals were favorable (> 95%), and graft function at 1 year was stable and similar between groups. Conclusion Despite taking lower MMF doses than previously studied, subjects on a PPI compared to an H2 RA were not at increased risk of acute rejection within 1 year posttransplantation. [ABSTRACT FROM AUTHOR]

Methionine metabolism is critical for epigenetic maintenance, redox homeostasis, and animal development. However, the regulation of methionine metabolism remains unclear. Here, we provide evidence that SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase, is critically involved in modulating methionine metabolism, thereby impacting maintenance of mouse embryonic stem cells ( mESCs) and subsequent embryogenesis. We demonstrate that SIRT1-deficient mESCs are hypersensitive to methionine restriction/depletion-induced differentiation and apoptosis, primarily due to a reduced conversion of methionine to S-adenosylmethionine. This reduction markedly decreases methylation levels of histones, resulting in dramatic alterations in gene expression profiles. Mechanistically, we discover that the enzyme converting methionine to S-adenosylmethionine in mESCs, methionine adenosyltransferase 2a ( MAT2a), is under control of Myc and SIRT1. Consistently, SIRT1 KO embryos display reduced Mat2a expression and histone methylation and are sensitive to maternal methionine restriction-induced lethality, whereas maternal methionine supplementation increases the survival of SIRT1 KO newborn mice. Our findings uncover a novel regulatory mechanism for methionine metabolism and highlight the importance of methionine metabolism in SIRT1-mediated mESC maintenance and embryonic development. [ABSTRACT FROM AUTHOR]

Dear Editor, Dermatologists are aware of the familial and hereditary components of melanoma. These genes, which are also associated with prostate cancer, pancreatic cancer, and melanoma risk, are included in melanoma genetic testing panels as they may lead to earlier, more frequent breast screening, prophylactic interventions, and more. [Extracted from the article]

Aim Understanding the scales over which land use affects animal populations is critical for conservation planning, and it can provide information about the mechanisms that underlie correlations between species distributions and land use. We used a citizen science database of anuran surveys to examine the relationship between road density, land use and the distribution of frogs and toads across spatial scales and regions of the United States. Location Eastern and Central United States. Methods We compiled data on anuran occupancy collected from 1999 to 2013 across 13 states in the North American Amphibian Monitoring Program, a citizen science survey of calling frogs. These data were indexed to measures of land use within buffers ranging from 300 m to 10 km. Results The negative effects of road density and development on anuran richness were strongest at the smallest scales (300-1000 m), and this pattern was consistent across regions. In contrast, the relationships of anuran richness to agriculture and forest cover were similar across local scales but varied among regions. Richness had a negative relationship with agriculture/forest loss in the Midwest but a positive relationship with agriculture in the Northeast. Anuran richness was more closely related to primary/secondary road density than to rural road density, and the negative effects of larger roads increased at smaller scales. Individual species differed in the scales over which roads and development affected their distributions, but these differences were not closely related to either body size or movement ability. Main conclusions This study further refines our understanding of the relationship between roads and amphibian populations and highlights the need for research into the specific mechanisms by which roads affect amphibians. Additionally, we find that relationships between land use and species richness can differ substantially across regions, demonstrating that one should use caution in generalizing from one region to another, even when species composition is similar. [ABSTRACT FROM AUTHOR]

Nociceptin/Orphanin FQ (N/ OFQ) is a 17 amino acid peptide whose receptor is designated ORL1 or nociceptin receptor ( NOP). We utilized a potent, selective, and orally bioavailable antagonist with documented engagement with NOP receptors in vivo to assess antidepressant- and anxiolytic-related pharmacological effects of NOP receptor blockade along with measures of cognitive and motor impingement. LY2940094 ([2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol) displayed antidepressant-like behavioral effects in the forced-swim test in mice, an effect absent in NOP−/− mice. LY2940094 also augmented the behavioral effect of fluoxetine without changing target occupancies ( NOP and serotonin reuptake transporter [ SERT]). LY2940094 did not have effects under a differential-reinforcement of low rate schedule. Although anxiolytic-like effects were not observed in some animal models (conditioned suppression, 4-plate test, novelty-suppressed feeding), LY2940094 had effects like that of anxiolytic drugs in three assays: fear-conditioned freezing in mice, stress-induced increases in cerebellar cGMP in mice, and stress-induced hyperthermia in rats. These are the first reports of anxiolytic-like activity with a systemically viable NOP receptor antagonist. LY2940094 did not disrupt performance in either a 5-choice serial reaction time or delayed matching-to-position assay. LY2940094 was also not an activator or suppressor of locomotion in rodents nor did it induce failures of rotarod performance. These data suggest that LY2940094 has unique antidepressant- and anxiolytic-related pharmacological effects in rodents. Clinical proof of concept data on this molecule in depressed patients have been reported elsewhere. [ABSTRACT FROM AUTHOR]

Rafflesia species are endo-holoparasites of Tetrastigma (Vitaceae) vines. Despite receiving considerable attention because of their rarity, enormous flowers, and fascinating parasitic life style, surprisingly little is known about their host specificity and host preference. This lack of information prevents a better understanding of the evolution of the host-parasite associations and host-focused conservation management of these threatened plants. This study is the first comprehensive analysis of host specificity and preference in Rafflesia. A total of 180 host plants of 11 out of 13 species of Philippine Rafflesia as well as non-parasitized Tetrastigma plants from most areas where Rafflesia species have been found were included in our study. Morphological data and nuclear and plastid DNA sequence phylogenies were used to identify and distinguish Tetrastigma lineages. Our studies provide support for previous claims that Tetrastigma species are the exclusive hosts of Rafflesia. A total of eight lineages of Philippine Tetrastigma were identified of which six are hosts of Rafflesia. Most of these Tetrastigma lineages are hosts of multiple Rafflesia species. In addition, four Rafflesia species parasitize multiple Tetrastigma lineages. The finding that Tetrastigma lineages and Rafflesia species that are relatively common are involved in multiple host-parasite associations suggests that these Rafflesia species are less host-specific than previous studies indicated. However, because some sympatric Tetrastigma species are not among the observed host species, we tentatively conclude that Philippine Rafflesia show at least some degree of host specificity. Host phylogenies suggest that cospeciation might not have occurred in the diversification of Philippine Rafflesia and Tetrastigma. [ABSTRACT FROM AUTHOR]

Background: The Demoralization Scale (DS) was initially validated in 2004 to enable the measurement of demoralization in patients with advanced cancer. Subsequent shortcomings indicated the need for psychometric strengthening. Here, the authors report on the refinement and revalidation of the DS to form the DS-II, specifically reporting the scale's internal validity.Methods: Patients with cancer or other progressive diseases who were receiving palliative care (n = 211) completed a revised version of the 24-item DS and a measure of symptom burden (the Memorial Symptom Assessment Scale). Exploratory factor analysis and Rasch modeling were used to evaluate, modify, and revalidate the scale, providing information about dimensionality, suitability of response format, item fit, item bias, and item difficulty. Test-retest reliability was examined for 58 symptomatically stable patients at a 5-day follow-up.Results: Exploratory factor analysis supported a 22-item, 2-component model. Separate Rasch modeling of each component resulted in collapsing the response option categories and removing 3 items from each component. Both final 8-item subscales met Rasch model expectations and were appropriate to sum as a 16-item total score. The DS-II demonstrated internal consistency and test-retest reliability (Meaning and Purpose subscale: α = .84; intraclass correlation [ICC] = 0.68; Distress and Coping Ability subscale: α = .82; ICC = 0.82; total DS: α = .89; ICC = 0.80).Conclusions: The DS-II is a 3-point response, self-report scale comprising 16 items and 2 subscales. Given its revalidation, psychometric strengthening, and simplification, the DS-II is an improved and more practical measure of demoralization for research and clinical use. External validation of the DS-II will be reported subsequently. Cancer 2016;122:2251-9. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Fras1 encodes an extracellular matrix protein that is critical for the establishment of the epidermal basement membrane during gestation. In humans, mutations in FRAS1 cause Fraser Syndrome (FS), a pleiotropic condition with many clinical presentations such as limb, eye, kidney, and craniofacial deformations. Many of these defects are mimicked by loss of Fras1 in mice, and are preceded by the formation of epidermal blisters in utero. Results: In this study, we identified a novel ENU-derived rounded foot ( rdf) mouse mutant with highly penetrant hindlimb soft-tissue syndactyly, among other structural defects. Mapping and sequencing revealed that rdf is a novel loss-of-function nonsense allele of Fras1 ( Fras1 rdf). Focusing on the limb, we found that the Fras1 rdf syndactyly phenotype originates from loss of interdigital cell death (ICD). Despite normal expression of bone morphogenetic protein (BMP) ligands and their receptors, the BMP downstream target gene Msx2, which is also necessary and sufficient to promote ICD, was down-regulated in the interdigital regions of Fras1 rdf hindlimb buds. Conclusions: The close correlation between limb bud epidermal blistering, decreased Msx2 expression, and reduced ICD in the Fras1 rdf hindlimb buds suggests that epithelium detachment from the mesenchyme may create a physical gap that interrupts the transmission of BMP, among other signals, resulting in soft tissue syndactyly. Developmental Dynamics 245:497-507, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

For animals with complex life cycles, conditions in the larval environment can have important effects that persist after metamorphosis. These carry-over effects may influence juvenile growth plasticity and have important fitness consequences., Small juvenile red-eyed treefrogs, Agalychnis callidryas, grow faster than larger ones. We examined to what extent this growth pattern is due to carry-over effects of intraspecific larval competition. In particular, we assessed larval gut plasticity and determined whether carry-over effects could persist given the extensive gut remodelling that occurs when herbivorous larvae transition to carnivorous juveniles., We reared larvae in mesocosms at low, medium and high densities and measured the size of both larval and juvenile guts, livers and fat bodies. We also monitored the timing of the onset of juvenile feeding post-metamorphosis and, after the onset of feeding, we measured intake rate and mean diet retention time. Finally, we measured juvenile metabolic rates to determine whether any organ size plasticity contributed to metabolic carry-over effects., Larval density had strong effects on larval morphology with higher densities increasing gut length and decreasing liver and fat body sizes. The effects of this plasticity carried over post-metamorphosis. High larval densities produced smaller juveniles with proportionately longer guts and extremely small livers and fat bodies. There were no apparent carry-over effects on size-specific metabolic rate., Differences in larval density were also associated with differences in post-metamorphic feeding. Small juveniles from high larval densities began feeding even before metamorphosis was complete, whereas large juveniles from low larval densities experienced a significant 2-week delay. Although juvenile body mass varied over threefold across treatments, once feeding was initiated, neither intake nor mean diet retention time scaled with body size., Overall, high larval densities produced small juveniles with very low lipid reserves that may have stimulated hyperphagia relative to larger juveniles. Longer guts carried over from the larval stage could facilitate this by allowing small juveniles to elevate intake without sacrificing diet retention time. Patterns of intake coupled with differences in the onset of feeding explain the size-dependent growth pattern previously reported in this and other species. [ABSTRACT FROM AUTHOR]

This paper draws upon an explanation of the proleptic, an understanding of time as being socially constructed within specific contexts, to interpret a series of dramatic sequences enacted in ethnodramatic pedagogy. The authors present two major arguments: (1) teachers can help students analyze the processes that influence and shape their identities by adopting a proleptic framework; (2) ethnodrama, a dramatic and dialogic approach to interpreting texts, creates an opportunity for students to evaluate the social forces that shape identity construction as they situate and reflect on texts within multiple contexts. The authors delineate the ways in which teachers can use ethnodrama to help students revise their understandings of the personal and cultural implications of texts by situating these understandings in different configurations of place, space, and time. [ABSTRACT FROM AUTHOR]

Aim To investigate the positive and negative aspects of family caregiving in two settings: community and aged care facility. Methods Postal questionnaires included the short Zarit Burden Interview ( ZBI) and a scale developed for this study: Positive Aspects of Caring Scale ( PACS). Results Analysis of responses of 90 carers showed high burden levels, with no difference between care settings. Carers of an older person with a cognitive condition showed higher burden. There was no association between carer burden and positive attitudes. Carers in community settings recorded lower levels of positive attitudes. Conclusion The two measures ( ZBI and PACS) may be a useful clinical tool to provide a balanced assessment of carers' experiences. The high burden found in both carer groups indicates the need for greater awareness, and improved support for carers, across the care continuum, from home to aged care facility. [ABSTRACT FROM AUTHOR]

Background/aim The Health Promoting Activities Scale ( HPAS) measures the frequency that mothers participate in self-selected leisure activities that promote health and wellbeing. The scale was originally validated on mothers of school-aged children with disabilities, and the current article extends this research using a comparative sample of mothers of typically developing school-aged children. Method Australian mothers ( N = 263) completed a questionnaire containing the HPAS, a measure of depression, anxiety and stress ( DASS-21) and questions concerning their weight, height, sleep quality and demographics. Statistical analysis assessed the underlying structure, internal consistency and construct validity of the HPAS. Inferential statistics were utilised to investigate the construct validity. Results Exploratory factor analysis supported the unidimensionality of the HPAS. It showed good internal consistency (Cronbach's alpha = 0.78). Significantly lower HPAS scores were recorded for women who were obese; had elevated levels of depression, anxiety and stress; had poor quality sleep or had heavy caring commitments. The mean HPAS score in this sample (M = 32.2) was significantly higher than was previously reported for women of children with a disability (M = 21.6: P < 0.001). Conclusions Further psychometric evaluation of the HPAS continues to support the HPAS as a sound instrument that measures the frequency that women participate in meaningful occupation that is associated with differences in mental health and wellbeing and other health indicators. [ABSTRACT FROM AUTHOR]

Aim This study investigated the internal construct validity and dimensionality of the Melbourne Assessment of Unilateral Upper Limb Function ( Melbourne Assessment), a widely-used measure of quality of upper limb movement, valid for children aged 2 years 6 months to 15 years with cerebral palsy. Method Rasch analysis was used to assess of Melbourne Assessment raw scores for 163 children (94 males, 69 females; mean age 8y, SD 3y 5mo). Analysis was undertaken on the full scale comprising 37 scores and on groups of scores separated into four distinct movement subscales: range of movement, accuracy, dexterity, and fluency. Tests were conducted to evaluate overall model fit, item fit, suitability of the response options, unidimensionality, and differential item functioning ( DIF) for sex, child age, and different raters. Results The results did not support the unidimensionality of the 37 -score scale. The four subscales showed adequate model fit after removal of some score items, and rescaling of others. The resulting subscales showed good internal consistency and no DIF for sex or child age. Interpretation This study provides empirical support for a revised version of the Melbourne Assessment which comprises 14 tasks and 30 movement scores grouped across four separate subscales. Further testing is required to assess the responsiveness of subscales to clinically important change. [ABSTRACT FROM AUTHOR]

Purpose To explore the onset and progression of spherical refractive error in a population with infantile nystagmus syndrome. Methods Retrospective refractive error data were obtained from 147 medical records of children with infantile nystagmus syndrome (albinism n = 98; idiopathic infantile nystagmus n = 49), attending a low vision clinic in Northern Ireland, over a 24 year period (1986-2010). Data were categorised by age to allow for comparisons with published studies. A prospective group of participants with Infantile nystagmus syndrome ( INS) [ n = 22 (albinism n = 18, idiopathic infantile nystagmus n = 4)] (aged 0-4) were also recruited. Cycloplegic streak retinoscopy was performed biannually, over a 3 year period. Spherical equivalent refractive error and most ametropic meridian were analysed. Results The mean spherical equivalent refractive errors for albinism and idiopathic infantile nystagmus groups (across all age categories) were hypermetropic, with highest levels demonstrated by the participants with albinism aged 1 ≤ 4 years (Mann-Whitney U test, p = 0.013). Mean most ametropic meridian was highest in the albinism group aged 1 ≤ 12 years (Mann-Whitney U test, p < 0.05). Individual data demonstrated relatively static spherical equivalent refractive errors over time. Prospective participants were hypermetropic at all visits and those with albinism had, on average, higher refractive errors than those with idiopathic infantile nystagmus ( IIN). No significant correlations were noted between visual acuity and spherical equivalent refractive errors or most ametropic meridian. Conclusions Hypermetropia is the most prevalent spherical refractive error in the INS population, irrespective of level of visual acuity. Individuals with infantile nystagmus syndrome fail to demonstrate typical patterns of emmetropisation, particularly in the presence of albinism. [ABSTRACT FROM AUTHOR]

Aim Sleep problems are more common among children with disabilities. Mothers are likely to provide night-time care. Mothers of children with disabilities are known to experience high levels of stress and mental health issues compared with other mothers. Relationships between a child's sleep problems, and chronic maternal sleep interruption and subjective health have not been researched. Method Cross-sectional mail-out survey with follow-up phone call was used. Instruments included the Short Form 36 version 2 and instruments that measured maternal, child and sleep characteristics. Descriptive statistics examined characteristics of participants and correlation, and Kruskal- Wallis test was used to determine important maternal and child characteristics around sleep issues. Results All mothers ( n = 152) cared for a school-aged child with a developmental disability including autism spectrum disorder ( n = 94) and cerebral palsy ( n = 29). Nearly half (49%) of the mothers were awoken more than 4 nights/week. Three distinct sleep groups were identified: no sleep interruption; sleep interruption once/night, 4 nights/week; and more frequent interruption. Mothers experiencing the most sleep interruptions reported significantly poorer health on six Short Form 36 version 2 dimensions. Night-time caregiving was associated with higher child care needs rather than children's diagnoses. Mothers who experienced more sleep interruption also participated less in health-promoting activities (active leisure, time with socially supportive others) during the day. Conclusion This study identifies a group of mothers with chronic sleep interruption and demonstrates related poor maternal subjective health and lower participation in health activities that may service to support maternal health. Mothers with children with the highest daytime care needs also experienced high night-time care responsibilities. Changes to service provision are recommended to identify mothers in need of additional supports and services. [ABSTRACT FROM AUTHOR]

This article describes a risk analysis used to inform resource allocation at the Tucson Sector of the U.S. Border Patrol, the busiest sector for alien and drug trafficking along the Southwest land border with Mexico. The model and methodology that underlie this analysis are generally applicable to many resource allocation decisions regarding the management of frequently occurring hazards, decisions regularly made by officials at all levels of the homeland security enterprise. The analysis was executed by agents without previous risk expertise working under a short time frame, and the findings from the analysis were used to inform several resource allocation decisions. [ABSTRACT FROM AUTHOR]

Most cases of human immunodeficiency virus ( HIV)-associated non- Hodgkin Lymphoma ( NHL) are of B-cell origin; T-cell NHLs are rarely reported. Within a single centre prospective cohort of 370 HIV- NHL, 17 (5%) were of T-cell origin (82% male; median age, 39 years). Median CD4+ cell count was 0·194 × 109/l and 41% had undetectable plasma HIV- RNA at lymphoma diagnosis. All patients received combination antiretroviral therapy during chemotherapy. All histological samples were centrally reviewed. The distribution of the histological subtypes differed from the general population with absence of angioimmunoblastic subtype. Lymphoma was disseminated in 14 patients, and seven patients had performance status >2. All patients received full-dose chemotherapy: eight standard and nine intensive regimens. Two patients who received intensive chemotherapy died during therapy. The complete remission rate was 53%; 62·5% with standard therapy and 44% with intensive therapy. After a median follow-up of 7·2 years, the median overall survival was 9·4 months. Most deaths (85%) occurred within the first year following diagnosis, as a consequence of lymphoma progression in 10/13 cases. In this rare but severe complication of HIV infection the use of intensive chemotherapy does not appear to be beneficial for response, with increased toxicity. [ABSTRACT FROM AUTHOR]

Background: Mammalian lung development consists of a series of precisely choreographed events that drive the progression from simple lung buds to the elaborately branched organ that fulfills the vital function of gas exchange. Strict transcriptional control is essential for lung development. Among the large number of transcription factors encoded in the mouse genome, only a small portion of them are known to be expressed and function in the developing lung. Thus a systematic investigation of transcription factors expressed in the lung is warranted. Results: To enrich for genes that may be responsible for regional growth and patterning, we performed a screen using RNA in situ hybridization to identify genes that show restricted expression patterns in the embryonic lung. We focused on the pseudoglandular stage during which the lung underergoes branching morphogenesis, a cardinal event of lung development. Using a genome-scale probe set that represents over 90% of the transcription factors encoded in the mouse genome, we identified 62 transcription factor genes with localized expression in the epithelium, mesenchyme, or both. Many of these genes have not been previously implicated in lung development. Conclusions: Our findings provide new starting points for the elucidation of the transcriptional circuitry that controls lung development. Developmental Dynamics 241:1432-1453, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: Charcot-Marie-Tooth disease (CMT) is a common heritable peripheral neuropathy. There is no treatment for any form of CMT, although clinical trials are increasingly occurring. Patients usually develop symptoms during the first 2 decades of life, but there are no established outcome measures of disease severity or response to treatment. We identified a set of items that represent a range of impairment levels and conducted a series of validation studies to build a patient-centered multi-item rating scale of disability for children with CMT. Methods: As part of the Inherited Neuropathies Consortium, patients aged 3 to 20 years with a variety of CMT types were recruited from the USA, United Kingdom, Italy, and Australia. Initial development stages involved definition of the construct, item pool generation, peer review, and pilot testing. Based on data from 172 patients, a series of validation studies were conducted, including item and factor analysis, reliability testing, Rasch modeling, and sensitivity analysis. Results: Seven areas for measurement were identified (strength, dexterity, sensation, gait, balance, power, endurance), and a psychometrically robust 11-item scale was constructed (CMT Pediatric Scale [CMTPedS]). Rasch analysis supported the viability of the CMTPedS as a unidimensional measure of disability in children with CMT. It showed good overall model fit, no evidence of misfitting items, and no person misfit, and it was well targeted for children with CMT. Interpretation: The CMTPedS is a well-tolerated outcome measure that can be completed in 25 minutes. It is a reliable, valid, and sensitive global measure of disability for children with CMT from the age of 3 years. ANN NEUROL 2012; [ABSTRACT FROM AUTHOR]

Aim: This research investigated the mental health of mothers of school-aged children with disabilities in Victoria, Australia. Methods: A mixed method triangulation design model was used to investigate the mental health of mothers ( n= 152) of school-aged children with developmental disabilities. Self-reported medical history and completion of the Short Form Health Survey Version 2 were used to collect data via mail-out survey and follow-up phone interview. Results: Mothers reported subjective mental health two standard deviations below other Australians and higher rates of depression and anxiety that other Australian women and the adult population in general. Half of participants reported that their health affected their ability to provide the care that their child needed, and half experienced frequent interrupted sleep secondary to the care of their child with a disability. Significantly poorer mental health was reported by mothers with a pre-school-aged child as well as a child with a disability ( P < 0.001), mothers with more than one child with a disability ( P= 0.038), mothers of children with autism spectrum disorder (ASD) ( P= 0.026), and mothers who recognised that their health affected care giving ( P < 0.001). Conclusions: The reported mental health of participants in this study indicates that further attention is needed to action health strategies to support mothers of children with disabilities. Health programs and policy that will identify mothers in need of assistance, as well as management strategies that will adequately support mental wellness in mothers is required in Australia. [ABSTRACT FROM AUTHOR]

Introduction: Research has been conducted over several years to develop a new off-road assessment battery referred to as the Occupational Therapy - Driver Off-Road Assessment Battery. This article documents the development of the Battery, and provides preliminary research evidence to support its content and predictive validity. Methods: Literature reviews and a focus group with nine driver assessor occupational therapists were undertaken, as well as data collection using the Occupational Therapy - Driver Off-Road Assessment Battery with 246 clients. A Classification and Regression Tree model was constructed to ascertain the predictive validity of the Battery, with fitness-to-drive as the outcome. Results: Twenty-one physical, 13 sensory and seven assessments of cognition/perception were identified as being reflective of the skills required for driving. Following rating of their psychometric properties, the best assessments were presented to focus group members. The driver assessors supported the inclusion of several assessments and encouraged the development of new assessments. A draft version of the Occupational Therapy - Driver Off-Road Assessment Battery was tested and found to have excellent predictive validity for client on-road performance of 82.6%. The Classification and Regression Tree model showed that client performance on tests included in the Battery should be used together, rather than in isolation, to support fitness-to-drive recommendations. Conclusion: This research identified the most suitable physical, sensory and cognitive assessments to include in the Occupational Therapy - Driver Off-Road Assessment Battery, and provided support for its validity. The development of this standardised battery assists driver assessors to accurately and consistently assess and report the off-road driving capacity of clients. [ABSTRACT FROM AUTHOR]

Hybridization is an important evolutionary factor in the diversification of many plant and animal species. Of particular interest is that historical hybridization resulting in the origin of new species or introgressants has occurred between species now geographically separated by great distances. Here, we report that Senecio massaicus, a tetraploid species native to Morocco and the Canary Islands, contains genetic material of two distinct, geographically separated lineages: a Mediterranean lineage and a mainly southern African lineage. A time-calibrated internal transcribed spacer phylogeny indicates that the hybridization event took place up to 6.18 Ma. Because the southern African lineage has never been recorded from Morocco or the Canary Islands, we hypothesize that it reached this area in the distant past, but never became permanently established. Interestingly, the southern African lineage includes S. inaequidens, a highly invasive species that has recently become widespread throughout Europe and was introduced at the end of the 19th century as a 'wool alien'. Our results suggest that this more recent invasion of Europe by S. inaequidens represents the second arrival of this lineage into the region. [ABSTRACT FROM AUTHOR]

Citation information: McClelland JF, O'Donoghue L, McIntyre M & Saunders KJ. Cup-to-disc and arteriole-to-venule ratios in children aged 6-7 and 12-13 years. Ophthalmic Physiol Opt 2011. doi: 10.1111/j.1475-1313.2011.00878.x Abstract Purpose: Little data exist detailing the normal cup-to-disc (CD) ratios and arteriole-to-venule (A/V) ratios of school age children. In addition, controversy exists in the literature regarding associations between CD and A/V ratios and visual and biometric parameters. The present study investigates the success rates of obtaining useable optic disc images from the portable Nidek Handheld Non-Mydriatic Fundus Camera (NM-200D) from school-age children and describes the distribution of CD ratios and A/V ratios in children aged 6-7 years of age and 12-13 years of age. In addition, the present study explores associations between CD and A/V ratios and a range of visual function and biometric parameters in children. Methods: Fundus images were obtained from 195 6-7 year old children and 227 12-13 year old children participating in a wider study of visual function in childhood (Northern Ireland Childhood Errors of Refraction Study or NICER). ImageJ software was used to obtain CD and A/V ratios from the digital images. Visual function measures and biometric parameters were also available for all participants including; cycloplegic refractive error, vision, corneal curvature, axial length, height and weight. Results: One hundred and eighty fundus images (92.3%) from the 6-7 year olds and 194 images (85.5%) from the 12-13 year olds children were considered useable. Analysis (one way anova) demonstrated statistically significant differences between CD ratios and A/V ratios between the age groups. Participants aged 12-13 years had larger CD ratios and smaller A/V ratios (mean CD ratio 0.37 ± 0.09, mean A/V ratio 0.75 ± 0.10) than 6-7 year old participants (mean CD ratio 0.30 ± 0.09, mean A/V ratio 0.78 ± 0.12). No significant associations were noted between CD ratios and A/V ratio and any visual, ocular or biometric parameters. Conclusions: The present study provides novel normative data on CD and A/V ratios in UK school age children for clinicians in practice. [ABSTRACT FROM AUTHOR]

As natural forest cover declines, planted forests have come to occupy an increasing percentage of the earth's surface, yet we know little about their suitability as alternative habitat for wildlife. Although some primate species use planted forests, few studies have compared primate populations in natural and nearby planted forests. From March 2006 to July 2010, we conducted line transect surveys and assessed group sizes and compositions in natural and nearby 60-70 year old mixed indigenous planted forest to determine the densities of diurnal primate species ( Colobus guereza, Cercopithecus mitis, C. ascanius) in these two forest types at Isecheno, Kakamega Forest, Kenya. Line transect data were analyzed using the Encounter Rate, Whitesides, and Distance sampling methods, which all provided broadly consistent results. We found that all three diurnal primate species occupy both natural and planted forest at Isecheno. However, group densities of the two Cercopithecus species were 42-46% lower in planted than in natural forest. Colobus guereza achieved comparable group densities in the two forest types, although the species is found in smaller groups, and thus at lower (35%) individual density, in planted than in natural forest. Following a logging episode in the planted forest mid-way through our study, Cercopithecus ascanius group densities fell by 60% while C. mitis and Colobus guereza group densities remained stable over the next two years. Overall, our results suggest that while primate species vary in their response to habitat disturbance, planted forest has the potential to contribute to the conservation of some African monkey species. Even for the relatively flexible taxa in our study, however, 60-70 year old mixed indigenous planted forest failed to support densities comparable to those in nearby natural forest. From the perspective of Kakamega's primates, planted forests may supplement natural forest, but are not an adequate replacement for it. Am. J. Primatol. 73:1-14, 2011. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Cytochrome P450 (CYP) epoxygenases CYP2C8 and CYP2J2 generate epoxyeicosatrienoic acids (EETs) from arachidonic acid. Mice with expression of CYP2J2 in cardiomyocytes (αMHC-CYP2J2 Tr) or treated with synthetic EETs have increased functional recovery after ischemia/reperfusion (I/R); however, no studies have examined the role of cardiomyocyte- vs. endothelial-derived EETs or compared the effects of different CYP epoxygenase isoforms in the ischemic heart. We generated transgenic mice with increased endothelial EET biosynthesis (Tie2-CYP2C8 Tr and Tie2-CYP2J2 Tr) or EET hydrolysis (Tie2-sEH Tr). Compared to wild-type (WT), αMHC-CYP2J2 Tr hearts showed increased recovery of left ventricular developed pressure (LVDP) and decreased infarct size after I/R. In contrast, LVDP recovery and infarct size were unchanged in Tie2-CYP2J2 Tr and Tie2-sEH Tr hearts. Surprisingly, compared to WT, Tie2-CYP2C8 Tr hearts had significantly reduced LVDP recovery (from 21 to 14%) and increased infarct size after I/R (from 51 to 61%). Tie2-CYP2C8 Tr hearts also exhibited increased reactive oxygen species (ROS) generation, dihydroxyoctadecenoic acid (DiHOME) formation, and coronary resistance after I/R. ROS scavengers and CYP2C8 inhibition reversed the detrimental effects of CYP2C8 expression in Tie2-CYP2C8 Tr hearts. Treatment of WT hearts with 250 nM 9,10-DiHOME decreased LVDP recovery compared to vehicle (16 vs. 31%, respectively) and increased coronary resistance after I/R. These data demonstrate that increased ROS generation and enhanced DiHOME synthesis by endothelial CYP2C8 impair functional recovery andmask the beneficial effects of increased EET production following I/R. [ABSTRACT FROM AUTHOR]

Objective: The Hospital Anxiety and Depression Scale (HADS) is often used to screen for cancer caregivers' anxiety and depression, despite few studies examining the tool's psychometric performance within this population. The purpose of this article is to use Rasch analysis to assess the psychometric properties of the HADS in a sample of cancer caregivers. Methods: HADS was administered to 541 caregivers of a population-based sample of patients diagnosed with one of the eight most incident cancers in Australia. Rasch analysis was conducted using RUMM2020. Results: More than two-thirds of caregivers were women and most participants were married (95.9%) and caring for their spouse/partner with cancer (89.8%). The HADS-Anxiety (HADS-A) subscale showed good fit to the model, with appropriate internal consistency after removal of item 11. There were no disordered thresholds and no differential item functioning (DIF) for sex or age. To achieve satisfactory model fit for the HADS-Depression (HADS-D) subscale item 8 was removed due to DIF for sex and item 14 was rescored to resolve disordered thresholds. Analyses supported the unidimensionality of the individual subscales; however, there was no support for the combination of subscales to form a HADS-Total. Conclusions: The results of Rasch analysis support the use of a modified version of the HADS-A and HADS-D among cancer caregivers. Further research is needed to confirm these findings and identify revised clinical cut-points. Findings reinforce the need for clinicians and researchers to formally test the psychometric properties of the instruments that they intend to use with different samples. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study which proposed an operability-based methodology formulated in the Linear Programming (LP) framework to determine the feasible set of output constraints for non-square model predictive control (MPC) controllers. The study considered a steam methane reformer process example provided by Air Products and Chemicals and DuPont and addressed high-dimensional systems characterizing industrial problems to demonstrate the effectiveness of the proposed LP approach. Results show that constrained region of operation can be reduced.