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Objective: This study assessed whether adding a telephone care management protocol to usual aftercare improved the outcomes of veterans in the year after they were discharged from residential treatment for posttraumatic stress disorder (PTSD).Methods: In a multisite randomized controlled trial, 837 veterans entering residential PTSD treatment were assigned to receive either standard outpatient aftercare (N=425) or standard aftercare plus biweekly telephone monitoring and support (N=412) for three months after discharge. Symptoms of PTSD and depression, violence, substance use, and quality of life were assessed by self-report questionnaires at intake, discharge, and four and 12 months postdischarge. Treatment utilization was determined from the Department of Veterans Affairs administrative data.Results: Telephone case monitors reached 355 participants (86%) by phone at least once and provided an average of 4.5 of the six calls planned. Participants in the telephone care and treatment-as-usual groups showed similar outcomes on all clinical measures. Time to rehospitalization did not differ by condition. In contrast with prior studies reporting poor treatment attendance among veterans, participants in both telephone monitoring and treatment as usual completed a mental health visit an average of once every ten days in the year after discharge. Many participants had continuing problems despite high utilization of outpatient care.Conclusions: Telephone care management had little incremental value for patients who were already high utilizers of mental health services. Telephone care management could potentially be beneficial in settings where patients experience greater barriers to engaging with outpatient mental health care after discharge from inpatient treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Diagnostic errors in primary care are harmful but poorly studied. To facilitate the understanding of diagnostic errors in real-world primary care settings that use electronic health records (EHRs), this study explored the use of the situational awareness (SA) framework from aviation human factors research. METHODS: A mixed-methods study was conducted involving reviews of EHR data followed by semi-structured interviews of selected providers from two institutions in the USA. The study population included 380 consecutive patients with colorectal and lung cancers diagnosed between February 2008 and January 2009. Using a pre-tested data collection instrument, trained physicians identified diagnostic errors, defined as lack of timely action on one or more established indications for diagnostic work-up for lung and colorectal cancers. Twenty-six providers involved in cases with and without errors were interviewed. Interviews probed for providers' lack of SA and how this may have influenced the diagnostic process. RESULTS: Of 254 cases meeting inclusion criteria, errors were found in 30 of 92 (32.6%) lung cancer cases and 56 of 167 (33.5%) colorectal cancer cases. Analysis of interviews related to error cases revealed evidence of lack of one of four levels of SA applicable to primary care practice: information perception, information comprehension, forecasting future events, and choosing appropriate action based on the first three levels. In cases without error, application of the SA framework provided insight into processes involved in attention management. CONCLUSIONS: A framework of SA can help analyse and understand diagnostic errors in primary care settings that use EHRs. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) retinitis is a common opportunistic infection among patients with AIDS and still causes visual morbidity despite the wide spread usage of highly active antiretroviral therapy (HAART). The ubiquitous CMV pathogen contains a human interleukin-10 (IL-10) homolog in its genome and utilizes it to evade host immune reactions through an IL-10 receptor mediated immune-suppression pathway.Methods: Effects of IL-10R1, IL-10 and previously described AIDS restriction gene variants are investigated on the development of CMV retinitis in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort (N = 1284).Results: In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22- 31.54; P = .03) to CMV retinitis. In African Americans (n = 534), potential effects of IL-10 variants are observed.Conclusion: Host genetics may have a role in the occurrence of CMV retinitis in patients infected with HIV. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence supports a role for cell-mediated immunity in the pathogenesis of cardiovascular disease. Single-nucleotide polymorphisms (SNPs) in JAK3, STAT4, and STAT6 of the Janus kinase-signal transducer and activator of transcription (Jak-Stat) signal transduction pathway were examined for association with time to new cardiovascular events in incident dialysis patients from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study.Study Design: Prospective cohort study.Setting& Participants: 764 white (n = 518) and black (n = 246) participants from 79 dialysis centers.Predictor: SNPs in JAK3, STAT4, and STAT6 selected using a pairwise approach to identify a maximally informative set of tag SNPs for populations of European and African descent.Outcomes& Measurements: Cox proportional hazards models were used to estimate unadjusted and multivariable-adjusted hazard ratios (HRs) for incident cardiovascular disease events after dialysis therapy initiation associated with each race-specific SNP.Results: 2 European tag SNPs (rs3212780 and rs3213409) in JAK3 were associated with new cardiovascular disease events in white patients with unadjusted HRs of 1.92 (P < 0.001) and 1.82 (P = 0.07), respectively. One dual-tag SNP (rs3212752) in JAK3 was associated with new cardiovascular events in white patients with an unadjusted HR of 2.09 (P < 0.001) and in black patients with an HR of 2.07 (P = 0.007). SNP rs3213409 codes for a valine to isoleucine change at amino acid 722, a potentially functional mutation. SNPs in STAT4 and STAT6 were not associated with cardiovascular events after the initiation of dialysis therapy.Limitations: This study does not provide direct evidence for the mechanism of increased risk. Replication in independent cohorts is necessary.Conclusions: Genetic polymorphisms in the Jak-Stat signaling pathway are associated with an increased risk of new cardiovascular events in incident dialysis patients. [ABSTRACT FROM AUTHOR]

Background: Rare mutations in nephrosis 2 (NPHS2), encoding podocin, are found in patients with familial and sporadic steroid-resistant nephrotic syndrome and focal segmental glomerular sclerosis. The objective of this study is to assess the contribution of the commonly reported functional podocin polymorphism R229Q to kidney disease in the population at large and replicate a prior study of an association of R229Q and albuminuria in the general population.Study Design: Large sample of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based prospective study.Setting& Participants: 4,424 white and 3,746 black middle-aged adults.Predictor: Genotype at the R229Q polymorphism in podocin.Outcomes: Urinary albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) as measures of kidney damage/dysfunction.Measurements: Crude and multivariable adjusted linear and logistic regression models.Results: R229Q allele frequencies were 3.7% in 4,424 white and 0.6% in 3,746 black individuals. No significant association of R229Q with increased ACR or decreased eGFR was observed (adjusted odds ratio of ACR > or = 30 mg/g in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.84; adjusted odds ratio of eGFR < 60 mL/min/1.73 m(2) in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.83). As expected, the established kidney disease risk factors hypertension and diabetes mellitus were associated strongly with measures of kidney damage/dysfunction, but the R229Q polymorphism was not associated with an additional increase in kidney disease measures.Limitations: Single measurement of ACR, subsample of all ARIC participants.Conclusion: No significant association of the relatively rare R229Q variant and ACR or eGFR was found in either white or black individuals. The phenotypic effect of a variant as R229Q would have to be of great magnitude to meaningfully contribute to the risk of kidney disease on a population level. The importance of such variants in the general population, as well as replication studies, can be evaluated best in large community-based studies that allow for accounting of established disease risk factors. [ABSTRACT FROM AUTHOR]

We investigated the determinants of inpatient rehabilitation costs in the Department of Veterans Affairs (VA) and examined the relationship between length of stay (LOS) and discharge costs using data from VA and community rehabilitation hospitals. We estimated regression models to identify patient characteristics associated with specialized inpatient rehabilitation costs. VA data included 3,535 patients discharged from 63 facilities in fiscal year 2001. We compared VA costs to community rehabilitation hospitals using a sample from the Uniform Data System for Medical Rehabilitation of 190,112 patients discharged in 1999 from 697 facilities. LOS was a strong predictor of cost for VA and non-VA hospitals. Functional status, measured by Functional Independence Measure (FIM) scores at admission, was statistically significant but added little explanatory value after controlling for LOS. Although FIM scores were associated with LOS, FIM scores accounted for little variance in cost after controlling for LOS. These results are most applicable to researchers conducting cost-effectiveness analyses. [ABSTRACT FROM AUTHOR]

Apoptotic beta-cell death is central to the pathogenesis of type 1 diabetes and may be important in islet graft rejection. Despite this, genetic control of beta-cell apoptosis is only poorly understood. We report that inhibition of gene transcription sensitized beta-cells to tumor necrosis factor (TNF)-alpha-induced apoptosis, indicating the presence of a regulated antiapoptotic response. Using oligonucleotide microarrays and real-time PCR, we identified TNFAIP3/A20 as the most highly regulated antiapoptotic gene expressed in cytokine-stimulated human and mouse islets. Cytokine induction of A20 mRNA in primary islets and insulinoma cells was rapid and observed within 1 h, consistent with A20 being an immediate early response gene in beta-cells. Regulation of A20 was nuclear factor-kappaB (NF-kappaB)-dependent, two NF-kappaB sites within the A20 promoter were found to be necessary and sufficient for A20 expression in beta-cells. Activation of NF-kappaB by TNF receptor-associated factor (TRAF) 2, TRAF6, NF-kappaB-inducing kinase, or protein kinase D, which transduce signals downstream of Toll-like receptors, TNF receptors, and free radicals, respectively, were all potent activators of the A20 promoter. Moreover, A20 expression was induced in transplanted islets in vivo. Finally, A20 expression was sufficient to protect beta-cells from TNF-induced apoptosis. These data demonstrate that A20 is the cardinal antiapoptotic gene in beta-cells. Further, A20 expression is NF-kappaB dependent, thus linking islet proinflammatory gene responses with protection from apoptosis. [ABSTRACT FROM AUTHOR]

The mid-1990s saw dramatic changes in mental health care in the Department of Veterans Affairs (VA), the largest provider of such care in the United States. Spending for specialized inpatient mental health care fell 21 percent from 1995 to 2001, while spending for specialized outpatient care rose 63 percent. The shift from inpatient to outpatient care was accompanied by rapid increases in outpatient medication costs. Overall, the VA reduced the average cost (per VA user) of specialized mental health care by 22 percent while it increased the number of users of these services by 35 percent. [ABSTRACT FROM AUTHOR]

[gamma]-Hydroxybutyrate (GHB) and its precursor [gamma]-butyrolactone (GBL) are commonly abused drugs with a narrow therapeutic index. Therefore, overdoses occur readily with recreational use, and severe poisoning can occur after deliberate self-poisoning. We report the sequelae in a patient who ingested a massive dose of GBL, with suicidal intent. Severe metabolic acidosis and an asystolic cardiac arrest were successfully treated with standard resuscitation, supportive care, and continuous venovenous hemodiafiltration. Plasma GHB concentrations were the highest reported to date. The acidosis was attributed to rapid systemic absorption of GBL, followed by rapid metabolism to GHB. [ABSTRACT FROM AUTHOR]

Objective: This study estimated the loss in outpatient copayment revenue for the U.S. Department of Veterans Affairs (VA) health care system from a mandate for free care related to military sexual trauma. sMethods: A retrospective database analysis located all VA enrollees who screened positive for military sexual trauma and received related care in fiscal years 2006-2008. The analysis predicted which individuals would face copayments for care related to military sexual trauma with and without the mandate and the cost to the VA in lost copayments in the outpatient setting.Results: Over 97% of persons receiving outpatient care for military sexual trauma would face no copayment even in the absence of a free-care mandate. The net cost to the VA health care system is small, .01%-.04% of annual collections of outpatient copayments.Conclusions: Administrative data are readily available to estimate the cost of a VA mandate for free care. The case of military sexual trauma shows that the forgone revenue may be small even when the number of free encounters is very large. [ABSTRACT FROM AUTHOR]

• Badlands do not always control the export of sediments in intermittent streams. • At the annual scale, badlands supply less than half of the total sediment yield. • At season scale, sediment produced in badlands can be higher than the sediment yield. • Drainage network controls sediment export directly related with the flashiness. • Pulses will determine the role of the drainage network (i.e. source or sink) The objective of this paper is to analyse the production and the yield of fine sediment in a small mountain catchment (10 km2), characterised by patches of badlands (25% of the catchment area) and drained by intermittent streams. The study area is located in the Southern Central Pyrenees. The study is performed at multiple temporal scales to further highlight: (i) the effect of pulses in the transfer of water and fine sediment; (ii) the contribution of the sediment production from badlands to the sediment yield of the catchment; and (iii) the role of the drainage network as fine sediment source and sink. Significant correlations between meteorological and flow variables were found; specifically, the strongest positive relations were observed between stream flashiness, the duration of the period in which the stream is dry and the suspended sediment concentration. Results indicated that badlands do not always control the export of sediments. At the annual scale badlands supply around 40% of the total catchment sediment yield. Seasonally sediment produced in badlands can be higher than the amount exported at the catchment outlet, suggesting the channel network acts as a sink. In terms of sediment production, badlands represent around of 53% of the total production taking also into account agricultural fields and forest areas. Results emphasise the key role of the channel network on controlling pulses of sediment transfer, in direct relation to the intermittent character of the streams. The frequency and magnitude of such pulses determines the catchment Sediment Delivery Ratio (SDR), depending on whether the drainage network acts as a sediment sink or source. [ABSTRACT FROM AUTHOR]

Australian wild limes occur in highly diverse range of environments and are a unique genetic resource within the genus Citrus. Here we compare the haplotype-resolved genome assemblies of six Australian native limes, including four new assemblies generated using PacBio HiFi and Hi-C sequencing data. The size of the genomes was between 315 and 391 Mb with contig N50s from 29.5 to 35 Mb. Gene completeness of the assemblies was estimated to be from 98.4 to 99.3% and the annotations from 97.7 to 98.9% based upon BUSCO, confirming the high contiguity and completeness of the assembled genomes. High collinearity was observed among the genomes and the two haplotype assemblies for each species. Gene duplication and evolutionary analysis demonstrated that the Australian citrus have undergone only one ancient whole-genome triplication event during evolution. The highest number of species-specific and expanded gene families were found in C. glauca and they were primarily enriched in purine, thiamine metabolism, amino acids and aromatic amino acids metabolism which might help C. glauca to mitigate drought, salinity, and pathogen attacks in the drier environments in which this species is found. Unique genes related to terpene biosynthesis, glutathione metabolism, and toll-like receptors in C. australasica, and starch and sucrose metabolism genes in both C. australis and C. australasica might be important candidate genes for HLB tolerance in these species. Expanded gene families were not lineage specific, however, a greater number of genes related to plant-pathogen interactions, predominantly disease resistant protein, was found in C. australasica and C. australis., (© 2024. The Author(s).)

We describe the first total synthesis of the unusual cyclopropane-containing indole alkaloid (-)-rauvomine B via a strategy centered upon intramolecular cyclopropanation of a tetracyclic N -sulfonyltriazole. Preparation of this precursor evolved through two generations of synthesis, with the ultimately successful route involving a palladium-catalyzed stereospecific allylic amination, a cis -selective Pictet-Spengler reaction, and ring-closing metathesis as important bond-forming reactions. The key cyclopropanation step was found to be highly dependent on the structure and conformational strain of the indoloquinolizidine N -sulfonyltriazole precursor, the origins of which are explored computationally through DFT studies. Overall, our synthesis proceeds in 11 total steps and 2.4% yield from commercial materials.

The recently updated Society for Healthcare Epidemiology of America, the Infectious Diseases Society of America, and the Association of Professionals in Infection Control practice recommendations for methicillin-resistant Staphylococcus aureus (MRSA) prevention in acute care facilities list contact precautions (CPs) for patients known to be infected or colonized with MRSA as an "essential practice," meaning that it should be adopted in all acute care facilities. We argue that existing evidence on benefits and harms associated with CP do not justify this recommendation. There are no controlled trials that support broad use of CP for MRSA prevention. Data from hospitals that have discontinued CP for MRSA have found no impact on MRSA acquisition or infection. The burden and harms of CP remain concerning, including the environmental impact of increased gown and glove use. We suggest that CP be included among other "additional approaches" to MRSA prevention that can be implemented under specific circumstances (eg outbreaks, evidence of ongoing transmission despite application of essential practices)., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Changes in climate shift the geographic locations that are suitable for malaria transmission because of the thermal constraints on vector Anopheles mosquitos and Plasmodium spp. malaria parasites and the lack of availability of surface water for vector breeding. Previous Africa-wide assessments have tended to solely represent surface water using precipitation, ignoring many important hydrological processes. Here, we applied a validated and weighted ensemble of global hydrological and climate models to estimate present and future areas of hydroclimatic suitability for malaria transmission. With explicit surface water representation, we predict a net decrease in areas suitable for malaria transmission from 2025 onward, greater sensitivity to future greenhouse gas emissions, and different, more complex, malaria transmission patterns. Areas of malaria transmission that are projected to change are smaller than those estimated by precipitation-based estimates but are associated with greater changes in transmission season lengths.

Background: The finger lime (Citrus australasica), one of six Australian endemic citrus species shows a high natural phenotypic diversity and novel characteristics. The wide variation and unique horticultural features have made this lime an attractive candidate for domestication. Currently no haplotype resolved genome is available for this species. Here we present a high quality, haplotype-resolved reference genome for this species using PacBio HiFi and Hi-C sequencing., Results: Hifiasm assembly and SALSA scaffolding resulted in a collapsed genome size of 344.2 Mb and 321.1 Mb and 323.2 Mb size for the two haplotypes. The nine pseudochromosomes of the collapsed genome had an N50 of 35.2 Mb, 99.1% genome assembly completeness and 98.9% gene annotation completeness (BUSCO). A total of 41,304 genes were predicted in the nuclear genome. Comparison with C. australis revealed that 13,661 genes in pseudochromosomes were unique in C. australasica. These were mainly involved in plant-pathogen interactions, stress response, cellular metabolic and developmental processes, and signal transduction. The two genomes showed a syntenic arrangement at the chromosome level with large structural rearrangements in some chromosomes. Genetic variation among five C. australasica cultivars was analysed. Genes related to defense, synthesis of volatile compounds and red/yellow coloration were identified in the genome. A major expansion of genes encoding thylakoid curvature proteins was found in the C. australasica genome., Conclusions: The genome of C. australasica present in this study is of high quality and contiguity. This genome helps deepen our understanding of citrus evolution and reveals disease resistance and quality related genes with potential to accelerate the genetic improvement of citrus., (© 2024. The Author(s).)

Using data from the Veterans' Health Administration from 2010 to 2019, we examined the distribution and prevalence of community-acquired phenotypic extended-spectrum β-lactamase (ESBL) E. coli in the United States. ESBL prevalence slowly increased during the study period, and cluster analysis showed clustering in both urban and rural locations.

Land cover responses to climate change must be quantified for understanding Arctic climate, managing Arctic water resources, maintaining the health and livelihoods of Arctic societies and for sustainable economic development. This need is especially pressing in Greenland, where climate changes are amongst the most pronounced of anywhere in the Arctic. Ice loss from the Greenland Ice Sheet and from glaciers and ice caps has increased since the 1980s and consequently the proglacial parts of Greenland have expanded rapidly. Here we determine proglacial land cover changes at 30 m spatial resolution across Greenland during the last three decades. Besides the vastly decreased ice cover (- 28,707 km 2  ± 9767 km 2 ), we find a doubling in total areal coverage of vegetation (111% ± 13%), a quadrupling in wetlands coverage (380% ± 29%), increased meltwater (15% ± 15%), decreased bare bedrock (- 16% ± 4%) and increased coverage of fine unconsolidated sediment (4% ± 13%). We identify that land cover change is strongly associated with the difference in the number of positive degree days, especially above 6 °C between the 1980s and the present day. Contrastingly, absolute temperature increase has a negligible association with land cover change. We explain that these land cover changes represent local rapid and intense geomorphological activity that has profound consequences for land surface albedo, greenhouse gas emissions, landscape stability and sediment delivery, and biogeochemical processes., (© 2024. The Author(s).)

The psammaplysins are a unique class of brominated marine alkaloids bearing a signature 5/7-spiroisoxazoline-oxepine core linked to a variable tyramine-derived unit. Here, we report the total synthesis of several members of this family via a dipolar cycloaddition between an in situ generated nitrile oxide and an unusual seven-membered enediol diether dipolarophile. Carefully orchestrated oxidative transformation toward the fully functionalized spirocycle and direct coupling with tyramine-derived amines provides access to five representative family members, psammaplysins A, M, O, and Q and ceratinamide A, the latter four for the first time. Additionally, kinetic resolution of a late-stage intermediate enables the first asymmetric synthesis of (-)-psammaplysin A, thereby confirming its absolute configuration.

Total syntheses of the 5/5-spirocyclic indoline alkaloids (±)-spiroindimicins B, C, D, E, F, and G have been achieved via a modular approach. Our route features direct coupling of halogenated pyrrolemetal and isatin partners, Suzuki coupling to append the indole unit, Lewis acid-mediated spirocyclization, and divergent functionalization to give various family members. These syntheses are concise (six or seven steps from commercial materials) and highly amenable to analogue synthesis.

The Myrioneuron alkaloids are a relatively small family of plant-derived alkaloids that present an intriguing array of structural intricacy and biological properties. As such, these natural products have drawn interest from the synthetic community, resulting in creative total syntheses of several family members. This review showcases recent synthetic efforts towards these polycyclic alkaloids.

The orange subfamily (Aurantioideae) contains several Citrus species cultivated worldwide, such as sweet orange and lemon. The origin of Citrus species has long been debated and less is known about the Aurantioideae. Here, we compiled the genome sequences of 314 accessions, de novo assembled the genomes of 12 species and constructed a graph-based pangenome for Aurantioideae. Our analysis indicates that the ancient Indian Plate is the ancestral area for Citrus-related genera and that South Central China is the primary center of origin of the Citrus genus. We found substantial variations in the sequence and expression of the PH4 gene in Citrus relative to Citrus-related genera. Gene editing and biochemical experiments demonstrate a central role for PH4 in the accumulation of citric acid in citrus fruits. This study provides insights into the origin and evolution of the orange subfamily and a regulatory mechanism underpinning the evolution of fruit taste., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Fluoroquinolone resistance among Enterobacteriaceae is a notable challenge for appropriate empiric therapy in outpatient settings. We describe the spatial distribution of fluoroquinolone resistance and its chronological change between 2000 and 2017 in the nationwide Veterans' Health Administration system. We found spatially concentrated increasing prevalence in the 2000s, followed by spatial dispersion in the 2010s.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals 1 . These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample., (© 2023. The Author(s).)