Mating system and population genetic structure of the bulldog ant Myrmecia pavida

Understanding the evolution of the alternative mating strategies of monandry and polyandry is a fundamental problem in evolutionary biology because of the cost-benefit trade-offs associated with mating for females. The problem is particularly intriguing in the social insects because queens in most species appear to be obligately monandrous (i.e., only a single male fathers their offspring), while those in a minority of species have evolved high, and sometimes extreme, polyandry. One group which may shed particular insight is the ant subfamily Myrmeciinae (Myrmecia and Nothomyrmecia). Here we examine the population and colony genetic structure of the bulldog ant Myrmecia pavida CLARK, 1951 by genotyping offspring workers from 45 colonies. We find little evidence of geographic structuring or inbreeding in the population, indicating that the species outbreeds, most probably in mating swarms. We also find that queens of M pavida show moderately high polyandry, with 84% having mated with between two and seven males, and an overall mean observed mating frequency of 3.8. This is significantly higher than previously reported for queens of Nothomyrmecia macrops, in which most females mate singly. This was similar to that of M pyriformis, M brevinoda, and M pilosula, the three congenerics for which mating frequencies have recently been reported. The two genera in the Myrmeciinae therefore appear to show multiple transitions in mating frequency and further investigation of the subfamily may be highly informative for disentangling the forces driving the evolution of alternative mating strategies

Clinical Feasibility of Noninvasive Visualization of Lymphatic Flow with Principles of Spin Labeling MR Imaging: Implications for Lymphedema Assessment

Purpose To extend a commonly used noninvasive arterial spin labeling magnetic resonance (MR) imaging method for measuring blood flow to evaluate lymphatic flow. Materials and Methods All volunteers (n = 12) provided informed consent in accordance with institutional review board and HIPAA regulations. Quantitative relaxation time (T1 and T2) measurements were made in extracted human lymphatic fluid at 3.0 T. Guided by these parameters, an arterial spin labeling MR imaging approach was adapted to measure lymphatic flow (flow-alternating inversion-recovery lymphatic water labeling, 3 × 3 × 5 mm) in healthy subjects (n = 6; mean age, 30 years ± 1 [standard deviation]; recruitment duration, 2 months). Lymphatic flow velocity was quantified by performing spin labeling measurements as a function of postlabeling delay time and by measuring time to peak signal intensity in axillary lymph nodes. Clinical feasibility was evaluated in patients with stage II lymphedema (three women; age range, 43–64 years) and in control subjects with unilateral cuff-induced lymphatic stenosis (one woman, two men; age range, 31–35 years). Results Mean T1 and T2 relaxation times of lymphatic fluid at 3.0 T were 3100 msec ± 160 (range, 2930–3210 msec; median, 3200 msec) and 610 msec ± 12 (range, 598–618 msec; median, 610 msec), respectively. Healthy lymphatic flow (afferent vessel to axillary node) velocity was 0.61 cm/min ± 0.13 (n = 6). A reduction (P \u3c .005) in lymphatic flow velocity in the affected arms of patients and the affected arms of healthy subjects with manipulated cuff-induced flow reduction was observed. The ratio of unaffected to affected axilla lymphatic velocity (1.24 ± 0.18) was significantly (P \u3c .005) higher than the left-to-right ratio in healthy subjects (0.91 ± 0.18). Conclusion This work provides a foundation for clinical investigations whereby lymphedema etiogenesis and therapies may be interrogated without exogenous agents and with clinically available imaging equipment

Extending the reach of the Fire Effects Planning Framework by taking a critical approach to science delivery and application

The Fire Effects Planning Framework (FEPF), developed under JFSP project (99-1-3-16) “Wildland fuels management: evaluating and planning risks and benefits,” was formally completed in June 2004. FEPF is a logical framework that uses available data (e.g., local, LANDFIRE data) and existing software (e.g., GIS, Farsite, FlamMap, expert knowledge) to produce maps of probable fire effects during the pre-season or in advance of a fire front. The initial project included significant technology transfer activities. As that project concluded, however, we continued to receive requests for assistance from field managers (District, Forest and Regional Forest Service offices), international organizations (Interior West Fire Council), and national fire planning organizations (Fire Program Analysis). These requests sought more information about the tool, assistance with using it for hazardous fuels planning, and guidance for incorporating FEPF into regional training courses. To enable us to continue our outreach efforts, we initiated JFSP 05-4-1-20 “Extending the reach of the the Fire Effects Planning Framework by taking a critical approach to science delivery and application”. This funding allowed us to meet requests for assistance and participation while allowing us to identify and concentrate on the most valuable transfer mechanisms. Our goal was to observe how field managers think about and use the tool, learn who they think the primary audience is, and then revise our materials and activities accordingly. FEPF is the only analysis tool we know of that helps managers (land and fire) articulate probable ecologic effects of fire and integrate these into fire decision-making and assessment. The technology and data used by FEPF is widely available. The scientific basis for crosswalk determinations are grounded in best available science, transparent, and easily updated as new information becomes available. As the federal fire agencies move toward more comprehensive implementation of Appropriate Management Response, FEPF remains the only process that can quickly and consistently indicate areas and conditions where fire may be neutral, beneficial or harmful to natural resources of interest. Thus, it provides the only existing process to link emergency fire operations (from full suppression to wildland fire use) with land management plans, a requirement of federal oversight entities (e.g., OIG)

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Legal professionals and witness statements from people with a suspected mental health diagnosis

Individuals with mental health problems are considered to be part of a group labeled ‘vulnerable’ in forensic psychology literature and the legal system more generally. In producing witness statements, there are numerous guidelines in the UK, designed to facilitate the production of reliable and valid accounts by those deemed to be vulnerable witnesses. And yet, it is not entirely clear how mental health impacts on reliability and validity within the judicial system, partly due to the diversity of those who present with mental health difficulties. In this paper, we set out to explore how legal professionals operating in the UK understand the impact of mental distress on the practical production of witness testimonies. Twenty legal professionals, including police officers, judges, magistrates and detectives were involved in a semi-structured interview to examine their knowledge and experience of working with mental health problems, and how they approached and worked with this group. A thematic analysis was conducted on the data and specific themes relevant to the overall research question are presented. These include a) dilemmas and deficiencies in knowledge of mental health, b) the abandonment of diagnosis and c) barriers to knowledge: time restrictions, silence, professional identity and fear. Finally, we explore some of the implications of these barriers, with regard to professional practice

DNA strand break repair and neurodegeneration.

A number of DNA repair disorders are known to cause neurological problems. These disorders can be broadly characterised into early developmental, mid-to-late developmental or progressive. The exact developmental processes that are affected can influence disease pathology, with symptoms ranging from early embryonic lethality to late-onset ataxia. The category these diseases belong to depends on the frequency of lesions arising in the brain, the role of the defective repair pathway, and the nature of the mutation within the patient. Using observations from patients and transgenic mice, we discuss the importance of double strand break repair during neuroprogenitor proliferation and brain development and the repair of single stranded lesions in neuronal function and maintenance

High Risk of Unexpected Late Fetal Death in Monochorionic Twins Despite Intensive Ultrasound Surveillance: A Cohort Study

BACKGROUND: The rationale for fetal surveillance in monochorionic twin pregnancies is timely intervention to prevent the increased fetal/perinatal morbidity and mortality attributed to twin–twin transfusion syndrome and intrauterine growth restriction. We investigated the residual risk of fetal death after viability in otherwise uncomplicated monochorionic diamniotic twin pregnancies. METHODS AND FINDINGS: We searched an electronic database of 480 completed monochorionic pregnancies that underwent fortnightly ultrasound surveillance in our tertiary referral fetal medicine service between 1992 and 2004. After excluding pregnancies with twin–twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence, and monoamniotic and high-order multiple pregnancies, we identified 151 uncomplicated monochorionic diamniotic twin pregnancies with normal growth, normal liquor volume, and normal Doppler studies on fortnightly ultrasound scans. Ten unexpected intrauterine deaths occurred in seven (4.6%) of 151 previously uncomplicated monochorionic diamniotic pregnancies, within 2 wk of a normal scan, at a median gestational age of 34(+1) wk (weeks(+days); range 28(+0) to 36(+3)). Two of the five cases that underwent autopsy had features suggestive of acute late onset twin–twin transfusion syndrome, but no antenatal indicators of transfusional imbalance or growth restriction, either empirically or in a 1:3 gestation-matched case–control comparison. The prospective risk of unexpected antepartum stillbirth after 32 wk was 1/23 monochorionic diamniotic pregnancies (95% confidence interval 1/11 to 1/63). CONCLUSION: Despite intensive fetal surveillance, structurally normal monochorionic diamniotic twin pregnancies without TTTS or IUGR are complicated by a high rate of unexpected intrauterine death. This prospective risk of fetal death in otherwise uncomplicated monochorionic diamniotic pregnancies after 32 wk of gestation might be obviated by a policy of elective preterm delivery, which now warrants evaluation

VCAM-1-targeted MRI Improves Detection of the Tumor-brain Interface

PurposeDespite optimal local therapy, tumor cell invasion into normal brain parenchyma frequently results in recurrence in patients with solid tumors. The aim of this study was to determine whether microvascular inflammation can be targeted to better delineate the tumor-brain interface through vascular cell adhesion molecule-1 (VCAM-1)-targeted MRI.Experimental designIntracerebral xenograft rat models of MDA231Br-GFP (breast cancer) brain metastasis and U87MG (glioblastoma) were used to histologically examine the tumor-brain interface and to test the efficacy of VCAM-1-targeted MRI in detecting this region. Human biopsy samples of the brain metastasis and glioblastoma margins were examined for endothelial VCAM-1 expression.ResultsThe interface between tumor and surrounding normal brain tissue exhibited elevated endothelial VCAM-1 expression and increased microvessel density. Tumor proliferation and stemness markers were also significantly upregulated at the tumor rim in the brain metastasis model. T2*-weighted MRI, following intravenous administration of VCAM-MPIO, highlighted the tumor-brain interface of both tumor models more extensively than gadolinium-DTPA-enhanced T1-weighted MRI. Sites of VCAM-MPIO binding, evident as hypointense signals on MR images, correlated spatially with endothelial VCAM-1 upregulation and bound VCAM-MPIO beads detected histologically. These findings were further validated in an orthotopic medulloblastoma model. Finally, the tumor-brain interface in human brain metastasis and glioblastoma samples was similarly characterized by microvascular inflammation, extending beyond the region detectable using conventional MRI.ConclusionsThis work illustrates the potential of VCAM-1-targeted MRI for improved delineation of the tumor-brain interface in both primary and secondary brain tumors

Systematic Review of the Empirical Evidence of Study Publication Bias and Outcome Reporting Bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials

Pravastatin for early-onset pre-eclampsia:a randomised, blinded, placebo-controlled trial

Objective: Women with pre-eclampsia have elevated circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1). Statins can reduce sFlt-1 from cultured cells and improve pregnancy outcome in animals with a pre-eclampsia-like syndrome. We investigated the effect of pravastatin on plasma sFlt-1 levels during pre-eclampsia. Design: Blinded (clinician and participant), proof of principle, placebo-controlled trial. Setting: Fifteen UK maternity units. Population: We used a minimisation algorithm to assign 62 women with early-onset pre-eclampsia (24 +0–31 +6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. Primary outcome: Difference in mean plasma sFlt-1 levels over the first 3 days following randomisation. Results: The difference in the mean maternal plasma sFlt-1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days [interquartile range (IQR) 5–14 days] for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin. Conclusions: We found no evidence that pravastatin lowered maternal plasma sFlt-1 levels once early-onset pre-eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. Tweetable abstract: Pravastatin does not improve maternal plasma sFlt-1 or placental growth factor levels following a diagnosis of early preterm pre-eclampsia #clinicaltrial finds