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Premise of the study:
Microsatellite primers were developed for
Melaleuca argentea
(Myrtaceae) to evaluate genetic diversity and population genetic structure of this broadly distributed northern ...Australian riparian tree species.
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Methods and Results:
454 GS-FLX shotgun sequencing was used to obtain 5860 sequences containing putative microsatellite motifs. Two multiplex PCRs were optimized to genotype 11 polymorphic microsatellite loci. These loci were screened for variation in individuals from two populations in the Pilbara region, northwestern Western Australia. Overall, observed heterozygosities ranged from 0.27 to 0.86 (mean: 0.52) and the number of alleles per locus ranged from two to 13 (average: 4.3).
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Conclusions:
These microsatellite loci will be useful in future studies of the evolutionary history and population and spatial genetic structure in
M. argentea
, and inform the development of seed sourcing strategies for the species.
Antibodies are important reagents for research, diagnostics, and therapeutics. Many examples of chimeric proteins combining the specific target recognition of antibodies with complementing ...functionalities such as fluorescence, toxicity or enzymatic activity have been described. However, antibodies selected solely on the basis of their binding specificities are not necessarily ideal candidates for the construction of chimeras. Here, we describe a high throughput method based on yeast display to directly select antibodies most suitable for conversion to fluorescent chimera. A library of scFv binders was converted to a fluorescent chimeric form, by cloning thermal green protein into the linker between VH and VL, and directly selecting for both binding and fluorescent functionality. This allowed us to directly identify antibodies functional in the single chain TGP format, that manifest higher protein expression, easier protein purification, and one-step binding assays.
Mixed linear model (MLM) methods have proven useful in controlling for population structure and relatedness within genome-wide association studies. However, MLM-based methods can be computationally ...challenging for large datasets. We report a compression approach, called 'compressed MLM', that decreases the effective sample size of such datasets by clustering individuals into groups. We also present a complementary approach, 'population parameters previously determined' (P3D), that eliminates the need to re-compute variance components. We applied these two methods both independently and combined in selected genetic association datasets from human, dog and maize. The joint implementation of these two methods markedly reduced computing time and either maintained or improved statistical power. We used simulations to demonstrate the usefulness in controlling for substructure in genetic association datasets for a range of species and genetic architectures. We have made these methods available within an implementation of the software program TASSEL.
Abstract
In vitro display technologies based on phage and yeast have a successful history of selecting single-chain variable fragment (scFv) antibodies against various targets. However, single-chain ...antibodies are often unstable and poorly expressed in Escherichia coli. Here, we explore the feasibility of converting scFv antibodies to an intrinsically fluorescent format by inserting the monomeric, stable fluorescent protein named thermal green, between the light- and heavy-chain variable regions. Our results show that the scTGP format maintains the affinity and specificity of the antibodies, improves expression levels, allows one-step fluorescent assay for detection of binding and is a suitable reagent for epitope binning. We also report the crystal structure of an scTGP construct that recognizes phosphorylated tyrosine on FcεR1 receptor of the allergy pathway.
Aims
To synthesise the current, global evidence‐informed guidance that supports nurses and midwives to recognise and respond to intimate partner violence (IPV), and how these practices can be ...translated from face‐to‐face encounters to care that is delivered through telehealth.
Background
COVID‐19‐related social and physical distancing measures increase the risk for individuals who are socially isolated with partners who perpetuate violence. Providing support through telehealth is one strategy that can mitigate the pandemic of IPV, while helping patients and providers stay safe from COVID‐19.
Design and Methods
In this discursive paper, we describe how practical guidance for safely recognising and responding to IPV in telehealth encounters was developed. The ADAPT‐ITT (Assessment, Decisions, Administration, Production, Topical Experts, Integration, Testing, Training) framework was used to guide the novel identification and adaptation of evidence‐informed guidance. We focused on the first six stages of the ADAPT‐ITT framework.
Conclusions
This paper fills a gap in available guidance, specifically for IPV recognition and response via telehealth. We present strategies for prioritising safety and promoting privacy while initiating, managing or terminating a telehealth encounter with patients who may be at risk for or experiencing IPV. Strategies for assessment, planning and intervention are also summarised. System‐level responses, such as increasing equitable access to telecommunication technology, are also discussed.
Relevance to clinical practice
Integrating innovative IPV‐focused practices into telehealth care is an important opportunity for nurses and midwives during the current global COVID‐19 pandemic. There are also implications for future secondary outbreaks, natural disasters or other physically isolating events, for improving healthcare efficiency, and for addressing the needs of vulnerable populations with limited access to health care.
Deutetrabenazine (Austedo, Teva Pharmaceuticals) is a deuterated form of tetrabenazine. It is the first deuterated drug to receive US regulatory approval and is approved for treatment of chorea in ...Huntington’s disease and tardive dyskinesia. Two oral single dose studies comparing deutetrabenazine (25 mg) with tetrabenazine (25 mg) in healthy volunteers evaluated the impact of deuteration on pharmacokinetics of the active metabolites, alpha‐dihydrotetrabenazine (α‐HTBZ) and beta‐dihydrotetrabenazine (β‐HTBZ), metabolite profile, safety, and tolerability. In the two‐way, cross‐over study, the mean elimination half‐life of deuterated total (α + β)‐HTBZ was doubled compared with nondeuterated total (α + β)‐HTBZ, with a twofold increase in overall mean exposure (area under the concentration‐time curve from zero to infinity (AUC0–inf)) and a marginal increase in mean peak plasma concentration (Cmax). In the mass balance and metabolite profiling study, there were no novel plasma or urinary metabolites of 14C‐deutetrabenazine relative to 14C‐tetrabenazine. Specific deuteration in deutetrabenazine resulted in a superior pharmacokinetic profile and an increased ratio of active‐to‐inactive metabolites, attributes considered to provide significant benefits to patients.
Background. The excess morbidity and mortality related to catheter utilization at and immediately following dialysis initiation may simply be a proxy for poor prognosis. We examined hospitalization ...burden related to vascular access (VA) type among incident patients who received some predialysis care.
Methods. We identified a random sample of incident US Dialysis Outcomes and Practice Patterns Study hemodialysis patients (1996-2004) who reported predialysis nephrologist care. VA utilization was assessed at baseline and throughout the first 6 months on dialysis. Poisson regression was used to estimate the risk of all-cause and cause-specific hospitalizations during the first 6 months.
Results. Among 2635 incident patients, 60% were dialyzing with a catheter, 22% with a graft and 18% with a fistula at baseline. Compared to fistulae, baseline catheter use was associated with an increased risk of all-cause hospitalization adjusted relative risk (RR) = 1.30, 95% confidence interval (CI): 1.09-1.54 and graft use was not (RR = 1.07, 95% CI: 0.89-1.28). Allowing for VA changes over time, the risk of catheter versus fistula use was more pronounced (RR = 1.72, 95% CI: 1.42-2.08) and increased slightly for graft use (RR = 1.15, 95% CI: 0.94-1.41). Baseline catheter use was most strongly related to infection-related (RR = 1.47, 95% CI: 0.92-2.36) and VA-related hospitalizations (RR = 1.49, 95% CI: 1.06-2.11). These effects were further strengthened when VA use was allowed to vary over time (RR = 2.31, 95% CI: 1.48-3.61 and RR = 3.10, 95% CI: 1.95-4.91, respectively). A similar pattern was noted for VA-related hospitalizations with graft use.
Discussion. Among potentially healthier incident patients, hospitalization risk, particularly infection and VA-related, was highest for patients dialyzing with a catheter at initiation and throughout follow-up, providing further support to clinical practice recommendations to minimize catheter placement.
Background Limited data exist describing vascular access conversions during the first year on dialysis therapy or the effect of converting to and from a catheter on subsequent mortality risk. Study ...Design Retrospective cohort study. Setting & Participants We studied a random sample of incident US hemodialysis patients (initiated long-term dialysis < 30 days before study entry) in the Dialysis Outcomes and Practice Patterns Study (DOPPS; 1996-2004). Predictors At dialysis therapy initiation, we assessed vascular access type in use (arteriovenous fistula AVF, arteriovenous graft AVG, or catheter) and other patient characteristics. We characterized changes in vascular access type (conversions) by using regularly collected functional status information. Outcome & Measurements We assessed time to all-cause mortality. We first described conversions, then used time-dependent Cox regression to estimate mortality hazard ratios (HRs) for conversions from a catheter to a permanent vascular access (versus no conversion) and conversions from a permanent vascular access to a catheter (versus no conversion). Results The study included 4,532 patients; 69.2% were dialyzing with a catheter; 17.6%, with an AVG; and 13.1%, with an AVF. In patients initiating therapy with an AVF or AVG, 22% experienced a conversion (failure), and median times to first failure were 62 and 84 days, respectively. In catheter patients, 59% converted to an AVF/AVG (predominantly AVG 57%); median times to first conversion were 92 and 66 days, respectively. Conversion to a permanent access was associated with an adjusted mortality HR of 0.69 (95% confidence interval, 0.55 to 0.85). The effect was similar for conversion to an AVF or AVG, and these persisted across demographic groups and facilities with different conversion practices. Conversion from a permanent vascular access to a catheter was associated with an adjusted mortality HR of 1.81 (95% confidence interval, 1.22 to 2.68). Limitations Potential for residual confounding because of unmeasured factors influencing decision to convert. Conclusion Vascular access conversions are common in incident patients. Continued efforts to increase early nephrologist referral and permanent vascular access placement may help decrease mortality risk in incident dialysis patients.
We describe a case of cerebral trichomoniasis in a neonate in whom seizures and multiorgan failure developed during treatment for staphylococcal sepsis. Brain abscesses were identified with cranial ...sonography, and Trichomonas vaginalis was isolated from cerebrospinal fluid samples. The patient died despite metronidazole therapy.
Deutetrabenazine (Austedo, Teva), an approved treatment of chorea in Huntington's disease and tardive dyskinesia in adult patients, is a rationally designed deuterated form of tetrabenazine. Two ...studies assessed the pharmacokinetics and safety of deutetrabenazine compared with tetrabenazine, and the effects of food on absorption of the deuterated active metabolites, α‐dihydrotetrabenazine (α‐HTBZ) and β‐dihydrotetrabenazine (β‐HTBZ). One study was an open‐label 2‐part study in healthy volunteers; the first part included a crossover single dose of two 15 mg candidate deutetrabenazine formulations in fed and fasted states compared with tetrabenazine 25 mg in the fasted state, and the second part included single and repeated dosing of the commercial formulation of deutetrabenazine (7.5, 15, and 22.5 mg) compared with tetrabenazine 25 mg. The second study was an open‐label 5‐way crossover study in healthy volunteers (n = 32) to evaluate relative bioavailability of 4 dose levels of the commercial formulation of deutetrabenazine (6, 12, 18, and 24 mg) with a standard meal and 18 mg with a high‐fat meal. Both studies confirmed longer half‐lives for active metabolites and lower peak‐to‐trough fluctuations for the sum of the metabolites (total α+β‐HTBZ) following deutetrabenazine compared with tetrabenazine (3‐ to 4‐fold and 11‐fold, respectively) in steady‐state conditions. Deutetrabenazine doses estimated to provide total (α+β)‐HTBZ exposure comparable to tetrabenazine 25 mg were 11.4‐13.2 mg. Food had no effect on exposure to total (α+β)‐HTBZ, as measured by AUC. Although the total (α+β)‐HTBZ Cmax of deutetrabenazine was increased by ≈50% in the presence of food, it remained lower than that of tetrabenazine.
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