Molecular Phylogenetics of the Genus Neoconocephalus (Orthoptera, Tettigoniidae) and the Evolution of Temperate Life Histories

BACKGROUND:The katydid genus Neoconocephalus (25+ species) has a prominent acoustic communication system and occurs in large parts of the Neotropics and Nearctic. This group has been subject of numerous behavioral, physiological, and evolutionary studies of its acoustic communication system. Two distinct life histories occur in this group: The tropical life history incorporates multiple generations/year and direct egg development without environmental triggers. Temperate life history is characterized by overwintering in the egg stage, cold trigger of egg development, and one generation/year. This study reconstructs the phylogenetic relationships within the genus to (1) determine the evolutionary history of the temperate life history, and (2) to support comparative studies of evolutionary and physiological problems in this genus. METHODOLOGY/PRINCIPAL FINDINGS:We used Amplified Fragment Length Polymorphisms (AFLP), and sequences of two nuclear loci and one mitochondrial locus to reconstruct phylogenetic relationships. The analysis included 17 ingroup and two outgroup species. AFLP and mitochondrial data provided resolution at the species level while the two nuclear loci revealed only deeper nodes. The data sets were combined in a super-matrix to estimate a total evidence tree. Seven of the temperate species form a monophyletic group; however, three more temperate species were placed as siblings of tropical species. CONCLUSIONS/SIGNIFICANCE:Our analyses support the reliability of the current taxonomic treatment of the Neoconocephalus fauna of Caribbean, Central, and North America. Ancestral state reconstruction of life history traits was not conclusive, however at least four transitions between life histories occurred among our sample of species. The proposed phylogeny will strengthen conclusions from comparative work in this group

Individualized Cost-Effectiveness Analysis

John Ioannidis and Alan Garber discuss how to use incremental cost-effectiveness ratios (ICER) and related metrics so they can be useful for decision-making at the individual level, whether used by clinicians or individual patients

Prevalence and predictors of hospital prealerting in acute stroke: a mixed methods study.

BACKGROUND: Thrombolysis can significantly reduce the burden of stroke but the time window for safe and effective treatment is short. In patients travelling to hospital via ambulance, the sending of a 'prealert' message can significantly improve the timeliness of treatment. OBJECTIVE: Examine the prevalence of hospital prealerting, the extent to which prealert protocols are followed and what factors influence emergency medical services (EMS) staff's decision to send a prealert. METHODS: Cohort study of patients admitted to two acute stroke units in West Midlands (UK) hospitals using linked data from hospital and EMS records. A logistic regression model examined the association between prealert eligibility and whether a prealert message was sent. In semistructured interviews, EMS staff were asked about their experiences of patients with suspected stroke. RESULTS: Of the 539 patients eligible for this study, 271 (51%) were recruited. Of these, only 79 (29%) were eligible for prealerting according to criteria set out in local protocols but 143 (53%) were prealerted. Increasing number of Face, Arm, Speech Test symptoms (1 symptom, OR 6.14, 95% CI 2.06 to 18.30, p=0.001; 2 symptoms, OR 31.36, 95% CI 9.91 to 99.24, p<0.001; 3 symptoms, OR 75.84, 95% CI 24.68 to 233.03, p<0.001) and EMS contact within 5 h of symptom onset (OR 2.99, 95% CI 1.37 to 6.50 p=0.006) were key predictors of prealerting but eligibility for prealert as a whole was not (OR 1.92, 95% CI 0.85 to 4.34 p=0.12). In qualitative interviews, EMS staff displayed varying understanding of prealert protocols and described frustration when their interpretation of the prealert criteria was not shared by ED staff. CONCLUSIONS: Up to half of the patients presenting with suspected stroke in this study were prealerted by EMS staff, regardless of eligibility, resulting in disagreements with ED staff during handover. Aligning the expectations of EMS and ED staff, perhaps through simplified prealert protocols, could be considered to facilitate more appropriate use of hospital prealerting in acute stroke

Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal

Mounting evidence suggests that there is frequently considerable variation in the risk of the outcome of interest in clinical trial populations. These differences in risk will often cause clinically important heterogeneity in treatment effects (HTE) across the trial population, such that the balance between treatment risks and benefits may differ substantially between large identifiable patient subgroups; the "average" benefit observed in the summary result may even be non-representative of the treatment effect for a typical patient in the trial. Conventional subgroup analyses, which examine whether specific patient characteristics modify the effects of treatment, are usually unable to detect even large variations in treatment benefit (and harm) across risk groups because they do not account for the fact that patients have multiple characteristics simultaneously that affect the likelihood of treatment benefit. Based upon recent evidence on optimal statistical approaches to assessing HTE, we propose a framework that prioritizes the analysis and reporting of multivariate risk-based HTE and suggests that other subgroup analyses should be explicitly labeled either as primary subgroup analyses (well-motivated by prior evidence and intended to produce clinically actionable results) or secondary (exploratory) subgroup analyses (performed to inform future research). A standardized and transparent approach to HTE assessment and reporting could substantially improve clinical trial utility and interpretability

Predicting Out-of-Office Blood Pressure in the Clinic for the Diagnosis of Hypertension in Primary Care An Economic Evaluation

Clinical guidelines in the United States and United Kingdom recommend that individuals with suspected hypertension should have ambulatory blood pressure (BP) monitoring to confirm the diagnosis. This approach reduces misdiagnosis because of white coat hypertension but will not identify people with masked hypertension who may benefit from treatment. The Predicting Out-of-Office Blood Pressure (PROOF-BP) algorithm predicts masked and white coat hypertension based on patient characteristics and clinic BP, improving the accuracy of diagnosis while limiting subsequent ambulatory BP monitoring. This study assessed the cost-effectiveness of using this tool in diagnosing hypertension in primary care. A Markov cost–utility cohort model was developed to compare diagnostic strategies: the PROOF-BP approach, including those with clinic BP ≥130/80 mm Hg who receive ambulatory BP monitoring as guided by the algorithm, compared with current standard diagnostic strategies including those with clinic BP ≥140/90 mm Hg combined with further monitoring (ambulatory BP monitoring as reference, clinic, and home monitoring also assessed). The model adopted a lifetime horizon with a 3-month time cycle, taking a UK Health Service/Personal Social Services perspective. The PROOF-BP algorithm was cost-effective in screening all patients with clinic BP ≥130/80 mm Hg compared with current strategies that only screen those with clinic BP ≥140/90 mm Hg, provided healthcare providers were willing to pay up to £20 000 ($26 000)/quality-adjusted life year gained. Deterministic and probabilistic sensitivity analyses supported the base-case findings. The PROOF-BP algorithm seems to be cost-effective compared with the conventional BP diagnostic options in primary care. Its use in clinical practice is likely to lead to reduced cardiovascular disease, death, and disability

Underwater Application of Quantitative PCR on an Ocean Mooring

The Environmental Sample Processor (ESP) is a device that allows for the underwater, autonomous application of DNA and protein probe array technologies as a means to remotely identify and quantify, in situ, marine microorganisms and substances they produce. Here, we added functionality to the ESP through the development and incorporation of a module capable of solid-phase nucleic acid extraction and quantitative PCR (qPCR). Samples collected by the instrument were homogenized in a chaotropic buffer compatible with direct detection of ribosomal RNA (rRNA) and nucleic acid purification. From a single sample, both an rRNA community profile and select gene abundances were ascertained. To illustrate this functionality, we focused on bacterioplankton commonly found along the central coast of California and that are known to vary in accordance with different oceanic conditions. DNA probe arrays targeting rRNA revealed the presence of 16S rRNA indicative of marine crenarchaea, SAR11 and marine cyanobacteria; in parallel, qPCR was used to detect 16S rRNA genes from the former two groups and the large subunit RuBisCo gene (rbcL) from Synecchococcus. The PCR-enabled ESP was deployed on a coastal mooring in Monterey Bay for 28 days during the spring-summer upwelling season. The distributions of the targeted bacterioplankon groups were as expected, with the exception of an increase in abundance of marine crenarchaea in anomalous nitrate-rich, low-salinity waters. The unexpected co-occurrence demonstrated the utility of the ESP in detecting novel events relative to previously described distributions of particular bacterioplankton groups. The ESP can easily be configured to detect and enumerate genes and gene products from a wide range of organisms. This study demonstrated for the first time that gene abundances could be assessed autonomously, underwater in near real-time and referenced against prevailing chemical, physical and bulk biological conditions

An endoscopic modification of the simultaneous ‘above and below’ approach to large pituitary adenomas

Surgical resections of large-to-giant pituitary adenomas (PA) are technically challenging procedures. Tumors with a fibrous consistency or ‘hour-glass’ configurations are particularly difficult to remove completely and safely through the transsphenoidal route alone. Although the transcranial approach can facilitate the removal of a large suprasellar mass, it may be associated with significant bleeding within the intradural space. A simultaneous microscopic transcranial and transsphenoidal approach has been described as an alternative surgical strategy. We have further modified this ‘above and below’ approach by adopting endoscopic techniques for the transsphenoidal part of the procedure. This modified approach has the advantages of requiring only one operating microscope, and permitting freer maneuvers and easier orientation for both surgical teams. We present two patients successfully treated with this approach. Complete tumor removal was achieved and both patients achieved satisfactory functional recovery

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

Funding: RTM is supported by a Wellcome Trust Intermediate Clinical Fellowship (grant no: 098522), https://wellcome.ac.uk/what-we-do/directories/intermediate-clinical-fellowships-people-funded. TWK is supported by Engineering and Physical Sciences Research Council grant EP/P015638/1, http://gow.epsrc.ac.uk/NGBOViewGrant.aspx?GrantRef=EP/P015638/1.The accuracy of Follicle Stimulating Hormone as a predictor of azoospermia in adult survivors of childhood cancer is unclear, with conflicting results in the published literature. A systematic review and post hoc analysis of combined data (n = 367) were performed on all published studies containing extractable data on both serum Follicle Stimulating Hormone concentration and semen concentration in survivors of childhood cancer. PubMed and Medline databases were searched up to March 2017 by two blind investigators. Articles were included if they contained both serum FSH concentration and semen concentration, used World Health Organisation certified methods for semen analysis, and the study participants were all childhood cancer survivors. There was no evidence for either publication bias or heterogeneity for the five studies. For the combined data (n = 367) the optimal Follicle Stimulating Hormone threshold was 10.4 IU/L with specificity 81% (95% CI 76%–86%) and sensitivity 83% (95% CI 76%–89%). The AUC was 0.89 (95%CI 0.86–0.93). A range of threshold FSH values for the diagnosis of azoospermia with their associated sensitivities and specificities were calculated. This study provides strong supporting evidence for the use of serum Follicle Stimulating Hormone as a surrogate biomarker for azoospermia in adult males who have been treated for childhood cancer.Publisher PDFPeer reviewe

Giant capsids from lattice self-assembly of cyclodextrin complexes

Proteins can readily assemble into rigid, crystalline and functional structures such as viral capsids and bacterial compartments. Despite ongoing advances, it is still a fundamental challenge to design and synthesize protein-mimetic molecules to form crystalline structures. Here we report the lattice self-assembly of cyclodextrin complexes into a variety of capsidlike structures such as lamellae, helical tubes and hollow rhombic dodecahedra. The dodecahedral morphology has not hitherto been observed in self-assembly systems. The tubes can spontaneously encapsulate colloidal particles and liposomes. The dodecahedra and tubes are respectively comparable to and much larger than the largest known virus. In particular, the resemblance to protein assemblies is not limited to morphology but extends to structural rigidity and crystallinity-a well-defined, 2D rhombic lattice of molecular arrangement is strikingly universal for all the observed structures. We propose a simple design rule for the current lattice self-assembly, potentially opening doors for new protein-mimetic materials