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OBJECTIVE: To describe and identify predictors of 12-month outcomes of serious orthopaedic injuries due to sport and active recreation. DESIGN: Prospective cohort study with 12-month follow-up. SETTING: Two Level 1 adult trauma centers in Victoria, Australia. PARTICIPANTS: A total of 366 adults admitted to two Level 1 trauma centers for an orthopaedic sport and active recreation injury between August 2003 and March 2006. Patients were captured by the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), followed up at 12 months, and were free of moderate to severe disability prior to injury. ASSESSMENT OF RISK FACTORS: Independent variables assessed for predictors of outcome were sporting group, age, sex, marital status, education level, Injury Severity Score, injury patterns, and head injury status. MAIN OUTCOME MEASUREMENTS: The 12-item Short Form Health Survey and maximum pain scores. RESULTS: At 12 months postinjury, 22.8% of patients reported moderate to severe physical disability, 12.1% reported moderate to severe mental health disability, and 11.1% reported moderate to severe pain. There were significant differences in physical outcomes between sporting groups, with motor and equestrian sports reporting the worst physical outcomes. Multivariate analysis indentified increasing age (P = 0.010) and patterns of injury (P = 0.040) as significant predictors of a poor physical outcome at 12 months. No significant independent predictors of outcome for mental health and maximum pain at 12 months were identified. CONCLUSION: Almost one-quarter of participants reported moderate to severe physical disability at 12 months postinjury. Increasing age and patterns of injury were found to be significant predictors of a poor physical outcome at 12 months. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria are important respiratory pathogens in patients with cystic fibrosis (CF). For diagnosis, international guidelines recommend culture of sputum that has been decontaminated via chemical treatment. Fifty-six sputum samples from 32 patients known to be previously colonized or infected with NTM were subdivided, and the aliquots were subjected to six different decontamination strategies, followed by quantitative culture for NTM. Thirty sputum samples contained Mycobacterium abscessus complex (MABSC) and 11 contained Mycobacterium avium complex (MAC). Decontamination strategies included treatment with N-acetyl L-cysteine with 2% sodium hydroxide (NALC-NaOH), 4% NaOH, 1% chlorhexidine, 0.5 N sulfuric acid, 5% oxalic acid, double decontamination with NALC-NaOH, followed by 5% oxalic acid, and saline (0.85%) as a control. The samples were also cultured directly with no treatment. Treatment with NALC-NaOH resulted in an average reduction in colony count of 87% for MABSC when compared with direct culture. NaOH at 4% caused a 98.3% average reduction in colony count. All treatments that included NaOH resulted in colony counts that were statistically lower than those obtained from direct culture or the saline-treated control (p < 0.05). Standard treatments using sulfuric or oxalic acids were less deleterious, but still resulted in an average reduction in colony count of at least 30%. The viability of MAC was much less affected by most decontamination treatments. In conclusion, the viability of MABSC was severely compromised by standard decontamination regimens. This supports recent evidence showing that optimal recovery of MABSC is achieved by culture on an appropriate selective agar without decontamination of sputum samples.

The ‘alternate wetting and drying’ (AWD) technology for rice is a water-saving technology with a high greenhouse gas (GHG) mitigation potential. The Philippine government attempts to disseminate AWD in all national irrigation systems in order to adapt to increasingly scarce water resources. This article describes how a model for climatic AWD suitability assessment developed by the International Rice Research Institute (IRRI) is suited for a national assessment of the Philippines, and country-scale climatic suitability maps for AWD are develop for wet and dry season. Furthermore, how the assessment can be used to estimate potential GHG emission savings is illustrated. Results show that a maximum of 60% of the rice area of the Philippines is climatically suited to AWD, reaching more than 90% in the dry and 34% in the wet season. The potential, maximum annual reduction is around 265,000t of CH4 emissions from lowland rice in the Philippines, or around 15% of the country's annual emissions from the agriculture sector. The article concludes with recommendations on the use of this simple spatial water balance model for mitigation planning which offers a more spatially detailed, quantitative and transparent estimate of national GHG emissions in the rice sub-sector for rice producing countries.

In this paper, we present the linguistic and cultural description of the Brazilian Zeeuws-Flemish population in Espírito Santo, which today has no more than 20 speakers. The Zeeuws-Flemish speakers, hundreds of whom left Zeeland in 1858-1862, have faced hardship and difficulty in adaptation and integration into Brazilian society ever since their arrival, with their language threatened not only by Brazilian Portuguese, but also by Brazilian Pomeranian, somewhat of a lingua franca among the Germanic Protestant community in the region. In this paper we present a sociolinguistic survey of the Brazilian Zeeuws-Flemish language community and an overview of its linguistic features such as intra- and interspeaker allophony, lexical borrowing and calquing, relative pronoun neutralization, do-support, topic drop, complementizer fusion, and loss of diminutives. --- DOI: http://dx.doi.org/10.22409/gragoata.2017n42a852 --- Original in English.

Abstract Background Late onset sepsis (LOS) in preterm infants is associated with considerable morbidity and mortality. While studies have implicated gut bacteria in the aetiology of the disease, functional analysis and mechanistic insights are generally lacking. We performed temporal bacterial (n = 613) and metabolomic (n = 63) profiling on extensively sampled stool from 7 infants with LOS and 28 matched healthy (no LOS or NEC) controls. Results The bacteria isolated in diagnostic blood culture usually corresponded to the dominant bacterial genera in the gut microbiome. Longitudinal changes were monitored based on preterm gut community types (PGCTs), where control infants had an increased number of PGCTs compared to LOS infants (P = 0.011). PGCT 6, characterised by Bifidobacteria dominance, was only present in control infants. Metabolite profiles differed between LOS and control infants at diagnosis and 7 days later, but not 7 days prior to diagnosis. Bifidobacteria was positively correlated with control metabolites, including raffinose, sucrose, and acetic acid. Conclusions Using multi-omic analysis, we show that the gut microbiome is involved in the pathogenesis of LOS. While the causative agent of LOS varies, it is usually abundant in the gut. Bifidobacteria dominance was associated with control infants, and the presence of this organism may directly protect, or act as a marker for protection, against gut epithelial translocation. While the metabolomic data is preliminary, the findings support that gut development and protection in preterm infants is associated with increased in prebiotic oligosaccharides (e.g. raffinose) and the growth of beneficial bacteria (e.g. Bifidobacterium).

Lucy Seki é uma das pioneiras da pesquisa de línguas indígenas no Brasil. Fez bacharelado em História pela UFMG. Obteve seu Mestrado em Filologia (especialidade Língua e Literatura Russa) e PhD em Filologia (especialidade Línguas Indígenas Americanas) pela Universidade Patrice Lumumba (Moscou).

OBJECTIVES/GOALS: This project seeks to understand how personalized medicine can optimize care for patients with colorectal cancer. It identifies opportunities for personalized medicine to improve clinical outcomes, and uses cost-effectiveness analysis to assess the clinical and financial impact of this approach. METHODS/STUDY POPULATION: This project uses two methods to understand the impact of personalized medicine. First, this project has used SEER-Medicare data in conjunction with Clinical Pharmacogenetics Implementation Consortium guidelines to identify medications used by patients with colorectal cancer that can be impacted by genetic variants. This data will then be combined with population genetic variant rates to understand the likely impact screening for a given variant will have on medication response and adverse events. Medication use frequencies and genetic variant rates are then used to populate cost-effectiveness models that simulate the clinical and financial outcomes, identifying optimal genes to screen. RESULTS/ANTICIPATED RESULTS: The first result will be a comprehensive overview of treatment patterns for patients with colorectal cancer in the United States, as well as the treatments used for disease-induced comorbidities. The second result will be the identification of genetic variants based on population rates and medication utilization that should be screened in this patient population. The final result will be a breakdown of the clinical and financial outcomes associated with implementing screening for the identified genes. Preliminary results from a two-gene cost-effectiveness analysis demonstrates that screening for variants in those genes improves both clinical and financial outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: This project demonstrates how current treatment approaches can be optimized via personalized medicine. It uses epidemiological methods to identify opportunities to integrate genetic findings from other diseases, and uses cost-effectiveness analysis to understand the impact of transforming care. CONFLICT OF INTEREST DESCRIPTION: Stocks-Aurinia, Syndax, Adaptimmune, Rigel pharma

ABSTRACT Temperate bacteriophages are a common feature of Pseudomonas aeruginosa genomes, but their role in chronic lung infections is poorly understood. This study was designed to identify the diverse communities of mobile P. aeruginosa phages by employing novel metagenomic methods, to determine cross infectivity, and to demonstrate the influence of phage infection on antimicrobial susceptibility. Mixed temperate phage populations were chemically mobilized from individual P. aeruginosa, isolated from patients with cystic fibrosis (CF) or bronchiectasis (BR). The infectivity phenotype of each temperate phage lysate was evaluated by performing a cross-infection screen against all bacterial isolates and tested for associations with clinical variables. We utilized metagenomic sequencing data generated for each phage lysate and developed a novel bioinformatic approach allowing resolution of individual temperate phage genomes. Finally, we used a subset of the temperate phages to infect P. aeruginosa PAO1 and tested the resulting lysogens for their susceptibility to antibiotics. Here, we resolved 105 temperate phage genomes from 94 lysates that phylogenetically clustered into 8 groups. We observed disease-specific phage infectivity profiles and found that phages induced from bacteria isolated from more advanced disease infected broader ranges of P. aeruginosa isolates. Importantly, when infecting PAO1 in vitro with 20 different phages, 8 influenced antimicrobial susceptibility. This study shows that P. aeruginosa isolated from CF and BR patients harbors diverse communities of inducible phages, with hierarchical infectivity profiles that relate to the progression of the disease. Temperate phage infection altered the antimicrobial susceptibility of PAO1 at subinhibitory concentrations of antibiotics, suggesting they may be precursory to antimicrobial resistance. IMPORTANCE Pseudomonas aeruginosa is a key opportunistic respiratory pathogen in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. The genomes of these pathogens are enriched with mobile genetic elements including diverse temperate phages. While the temperate phages of the Liverpool epidemic strain have been shown to be active in the human lung and enhance fitness in a rat lung infection model, little is known about their mobilization more broadly across P. aeruginosa in chronic respiratory infection. Using a novel metagenomic approach, we identified eight groups of temperate phages that were mobilized from 94 clinical P. aeruginosa isolates. Temperate phages from P. aeruginosa isolated from more advanced disease showed high infectivity rates across a wide range of P. aeruginosa genotypes. Furthermore, we showed that multiple phages altered the susceptibility of PAO1 to antibiotics at subinhibitory concentrations.

Infective endocarditis is an uncommon microbial infection of the endocardial surface of the heart. Patients with structural heart disease, such as a ventricular septal defect, are at higher risk for infective endocarditis and clinicians must have a high index of suspicion in such patients presenting with recurrent fevers. We present a patient with a known ventricular septal defect presenting with recurrent fevers associated with migratory lung nodules following a “low‐risk” dental procedure without antibiotic prophylaxis. The unusual presentation delayed the diagnosis of the migratory lung lesions as septic pulmonary emboli and consequentially the diagnosis of ventricular septal defect related infective endocarditis. The patient made an uneventful recovery following antibiotic therapy and surgical intervention.

Clinical laboratories have adopted next generation sequencing (NGS) as a gold standard for the diagnosis of hereditary disorders because of its analytic accuracy, high throughput, and potential for cost-effectiveness. We describe the implementation of a single broad-based NGS sequencing assay to meet the genetic testing needs at the University of Minnesota. A single hybrid capture library preparation was used for each test ordered, data was informatically blinded to clinically-ordered genes, and identified variants were reviewed and classified by genetic counselors and molecular pathologists. We performed 2509 sequencing tests from August 2012 till December 2017. The diagnostic yield has remained steady at 25%, but the number of variants of uncertain significance (VUS) included in a patient report decreased over time with 50% of the patient reports including at least one VUS in 2012 and only 22% of the patient reports reporting a VUS in 2017 (p = .002). Among the various clinical specialties, the diagnostic yield was highest in dermatology (60% diagnostic yield) and ophthalmology (42% diagnostic yield) while the diagnostic yield was lowest in gastrointestinal diseases and pulmonary diseases (10% detection yield in both specialties). Deletion/duplication analysis was also implemented in a subset of panels ordered, with 9% of samples having a diagnostic finding using the deletion/duplication analysis. We have demonstrated the feasibility of this broad-based NGS platform to meet the needs of our academic institution by aggregating a sufficient sample volume from many individually rare tests and providing a flexible ordering for custom, patient-specific panels. Keywords: Next generation sequencing, Molecular diagnostics, Panel testing, Diagnostic yield, Variants of uncertain significance, Copy number variation

For fast-flying birds, the ability to respond to wind during landing is critical, as errors can lead to injury or even death. Nonetheless, landing ability, and its ecological significance, remain unstudied. We show that for auks, 60% of attempts to land at their cliff nests fail in a strong breeze (80% in near-gale winds). This is most likely because wind interferes with the ability to maintain flight control in the last phase of landing. Their extreme flight costs mean that the energetic penalty for multiple landing attempts is high. We propose that exposure, and ability to respond to, such conditions will influence the suitability of breeding habitat. In support of this (i) auk colonies appear to be orientated away from prevailing winds and (ii) landing success within colonies is higher on crowded ledges with more airspace for manoeuvring. More generally, the interplay between wind and flight capacities could impact breeding distributions across species and scales.

Introduction: Diffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50–90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively. Methods: We applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7 Telsa (7 T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns. Results: Ten adult patients with a histo-molecular (n = 9) or radiological (n = 1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/− 12.3 years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (p = .001), and increased peritumoural GluCEST contrast was associated with both recent seizures (p = .038) and drug refractory epilepsy (p = .029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (R = 0.89, p = .003) and a positive trend existed in the tumour voxel (R = 0.65, p = .113). Conclusion: This study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7 T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required. Keywords: Glutamate, Glioma, Epilepsy, GluCEST, Seizure, 7 T MRI

Abstract Background During minimally invasive pulmonary resection, both limited visualization and tactile feedback can make localization of pulmonary nodules and assessment for synchronous disease challenging. Intraoperative molecular imaging is an emerging technology that can enhance a surgeon’s ability to detect cancers at the time of resection. Case presentation In this report, we describe the application of a folate receptor-targeted, near infrared optical contrast agent (OTL38) for the detection of an invasive pulmonary adenocarcinoma. During molecular imaging, an otherwise undetectable synchronous nodule was also identified. This finding resulted in intraoperative upstaging and operative plan modifications. Conclusion This report marks the first successful utilization of a targeted, near infrared intraoperative molecular imaging probe useful for thoracic malignancies. This rapidly evolving technology may enhance the surgeon’s ability to perform a number of oncologic procedures including tumor localization, margin assessment and intraoperative staging.

Summary: Long-lived reservoirs of persistent HIV are a major barrier to a cure. CD4+ hematopoietic stem and progenitor cells (HSPCs) have the capacity for lifelong survival, self-renewal, and the generation of daughter cells. Recent evidence shows that they are also susceptible to HIV infection in vitro and in vivo. Whether HSPCs harbor infectious virus or contribute to plasma virus (PV) is unknown. Here, we provide strong evidence that clusters of identical proviruses from HSPCs and their likely progeny often match residual PV. A higher proportion of these sequences match residual PV than proviral genomes from bone marrow and peripheral blood mononuclear cells that are observed only once. Furthermore, an analysis of near-full-length genomes isolated from HSPCs provides evidence that HSPCs harbor functional HIV proviral genomes that often match residual PV. These results support the conclusion that HIV-infected HSPCs form a distinct and functionally significant reservoir of persistent HIV in infected people. : HIV causes an infection that persists even when optimal therapy is used. Zaikos et al. provide evidence that HIV-infected progenitor cells from the bone marrow can amplify virus through normal cellular growth pathways in some treated people. Keywords: HIV, latency, reservoir, virus, persistence, clonal, hematopoietic, human, defective, infectious

We have characterized and compared the structures of ergosterol- and cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes before and after interaction with the amphiphilic antifungal drug amphotericin B (AmB) using neutron reflection. AmB inserts into both pure POPC and sterol-containing membranes in the lipid chain region and does not significantly perturb the structure of pure POPC membranes. By selective per-deuteration of the lipids/sterols, we show that AmB extracts ergosterol but not cholesterol from the bilayers and inserts to a much higher degree in the cholesterol-containing membranes. Ergosterol extraction by AmB is accompanied by membrane thinning. Our results provide new insights into the mechanism and antifungal effect of AmB in these simple models of fungal and mammalian membranes and help understand the molecular origin of its selectivity and toxic side effects.