Thermal structure and exhumation history of the Lesser Himalaya in central Nepal

The Lesser Himalaya (LH) consists of metasedimentary rocks that have been scrapped off from the underthrusting Indian crust and accreted to the mountain range over the last ~20 Myr. It now forms a significant fraction of the Himalayan collisional orogen. We document the kinematics and thermal metamorphism associated with the deformation and exhumation of the LH, combining thermometric and thermochronological methods with structural geology. Peak metamorphic temperatures estimated from Raman spectroscopy of carbonaceous material decrease gradually from 520°–550°C below the Main Central Thrust zone down to less than 330°C. These temperatures describe structurally a 20°–50°C/km inverted apparent gradient. The Ar muscovite ages from LH samples and from the overlying crystalline thrust sheets all indicate the same regular trend; i.e., an increase from about 3–4 Ma near the front of the high range to about 20 Ma near the leading edge of the thrust sheets, about 80 km to the south. This suggests that the LH has been exhumed jointly with the overlying nappes as a result of overthrusting by about 5 mm/yr. For a convergence rate of about 20 mm/yr, this implies underthrusting of the Indian basement below the Himalaya by about 15 mm/yr. The structure, metamorphic grade and exhumation history of the LH supports the view that, since the mid-Miocene, the Himalayan orogen has essentially grown by underplating, rather than by frontal accretion. This process has resulted from duplexing at a depth close to the brittle-ductile transition zone, by southward migration of a midcrustal ramp along the Main Himalayan Thrust fault, and is estimated to have resulted in a net flux of up to 150 m^2/yr of LH rocks into the Himalayan orogenic wedge. The steep inverse thermal gradient across the LH is interpreted to have resulted from a combination of underplating and post metamorphic shearing of the underplated units

Beyond Leptin: Emerging Candidates for the Integration of Metabolic and Reproductive Function during Negative Energy Balance

Reproductive status is tightly coupled to metabolic state in females, and ovarian cycling in mammals is halted when energy output exceeds energy input, a metabolic condition known as negative energy balance. This inhibition of reproductive function during negative energy balance occurs due to suppression of gonadotropin-releasing hormone (GnRH) release in the hypothalamus. The GnRH secretagogue kisspeptin is also inhibited during negative energy balance, indicating that inhibition of reproductive neuroendocrine circuits may occur upstream of GnRH itself. Understanding the metabolic signals responsible for the inhibition of reproductive pathways has been a compelling research focus for many years. A predominant theory in the field is that the status of energy balance is conveyed to reproductive neuroendocrine circuits via the adipocyte hormone leptin. Leptin is stimulatory for GnRH release and lower levels of leptin during negative energy balance are believed to result in decreased stimulatory drive for GnRH cells. However, recent evidence found that restoring leptin to physiological levels did not restore GnRH function in three different models of negative energy balance. This suggests that although leptin may be an important permissive signal for reproductive function as indicated by many years of research, factors other than leptin must critically contribute to negative energy balance-induced reproductive inhibition. This review will focus on emerging candidates for the integration of metabolic status and reproductive function during negative energy balance

Establishing the liquid phase equilibrium of angrites to constrain their petrogenesis

Angrites are a series of differentiat-ed meteorites, extremely silica undersaturated and with unusally high Ca and Al contents [1]. They are thought to originate from a small planetesimal parent body of ~ 100-200 km in radius ([2-3]), can be either plutonic (i.e., cumulates) or volcanic (often referred to as quenched) in origin, and their old formation ages (4 to 11 Myr after CAIs) have made them prime anchors to tie the relative chronologies inferred from short-lived radionuclides (e.g., Al-Mg, Mn-Cr, Hf-W) to the absolute Pb-Pb clock [4]. They are also the most vola-tile element-depleted meteorites available, displaying a K-depletion of a factor of 110 relative to CIs

Phase correlation of laser waves with arbitrary frequency spacing

The theoretically predicted correlation of laser phase fluctuations in Lambda-type interaction schemes is experimentally demonstrated. We show, that the mechanism of correlation in a Lambda scheme is restricted to high frequency noise components, whereas in a double-$\Lambda$ scheme, due to the laser phase locking in closed-loop interaction, it extends to all noise frequencies. In this case the correlation is weakly sensitive to coherence losses. Thus the double-Lambda scheme can be used to correlate e.m. fields with carrier frequency differences beyond the GHz regime.Comment: 4 pages, 4 figure

Superconductivity-enhanced bias spectroscopy in carbon nanotube quantum dots

We study low-temperature transport through carbon nanotube quantum dots in the Coulomb blockade regime coupled to niobium-based superconducting leads. We observe pronounced conductance peaks at finite source-drain bias, which we ascribe to elastic and inelastic cotunneling processes enhanced by the coherence peaks in the density of states of the superconducting leads. The inelastic cotunneling lines display a marked dependence on the applied gate voltage which we relate to different tunneling-renormalizations of the two subbands in the nanotube. Finally, we discuss the origin of an especially pronounced sub-gap structure observed in every fourth Coulomb diamond

Belimumab : a technological advance for systemic lupus erythematosus patients? Report of a systematic review and meta-analysis

Objectives: To undertake a systematic review and meta-analysis to investigate clinical effectiveness of belimumab for patients with systemic lupus erythematosus (SLE) and antinuclear and/or anti-double-stranded DNA (dsDNA) autoantibodies. Methods: We searched eight electronic databases and reference lists for randomised controlled trials (RCTs) of belimumab against placebo or best supportive care. Quality assessment and random effects meta-analysis were undertaken. Design: A meta-analysis of RCTs. Participants: 2133 SLE patients. Primary and secondary outcome measures: SLE Responder Index (SRI) at week 52. Results: Three double-blind placebo-controlled RCTs (L02, BLISS-52 BLISS-76) investigated 2133 SLE patients. BLISS-52 and BLISS-76 trials recruited patients with antinuclear and/or anti-dsDNA autoantibodies and demonstrated belimumab effectiveness for the SRI at week 52. Ethnicity and geographical location of participants varied considerably between BLISS trials. Although tests for statistical heterogeneity were negative, BLISS-52 results were systematically more favourable for all measured outcomes. Meta-analysis of pooled 52-week SRI BLISS results showed benefit for belimumab (OR 1.63, 95% CI 1.27 to 2.09). By week 76, the primary SRI outcome in BLISS-76 was not statistically significant (OR 1.31, 95% CI 0.919 to 1.855)

Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer : a systematic review and overview of reviews

Background: Prophylactic aspirin has been considered to be beneficial in reducing the risks of heart disease and cancer. However, potential benefits must be balanced against the possible harm from side effects, such as bleeding and gastrointestinal (GI) symptoms. It is particularly important to know the risk of side effects when aspirin is used as primary prevention - that is when used by people as yet free of, but at risk of developing, cardiovascular disease (CVD) or cancer. In this report we aim to identify and re-analyse randomised controlled trials (RCTs), systematic reviews and meta-analyses to summarise the current scientific evidence with a focus on possible harms of prophylactic aspirin in primary prevention of CVD and cancer. Objectives: To identify RCTs, systematic reviews and meta-analyses of RCTs of the prophylactic use of aspirin in primary prevention of CVD or cancer. To undertake a quality assessment of identified systematic reviews and meta-analyses using meta-analysis to investigate study-level effects on estimates of benefits and risks of adverse events; cumulative meta-analysis; exploratory multivariable meta-regression; and to quantify relative and absolute risks and benefits. Methods: We identified RCTs, meta-analyses and systematic reviews, and searched electronic bibliographic databases (from 2008 September 2012) including MEDLINE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Centre for Reviews and Dissemination, and Science Citation Index. We limited searches to publications since 2008, based on timing of the most recent comprehensive systematic reviews. Results: In total, 2572 potentially relevant papers were identified and 27 met the inclusion criteria. Benefits of aspirin ranged from 6% reduction in relative risk (RR) for all-cause mortality [RR 0.94, 95% confidence interval (CI) 0.88 to 1.00] and 10% reduction in major cardiovascular events (MCEs) (RR 0.90, 95% CI 0.85 to 0.96) to a reduction in total coronary heart disease (CHD) of 15% (RR 0.85, 95% CI 0.69 to 1.06). Reported pooled odds ratios (ORs) for total cancer mortality ranged between 0.76 (95% CI 0.66 to 0.88) and 0.93 (95% CI 0.84 to 1.03). Inclusion of the Women's Health Study changed the estimated OR to 0.82 (95% CI 0.69 to 0.97). Aspirin reduced reported colorectal cancer (CRC) incidence (OR 0.66, 95% CI 0.90 to 1.02). However, including studies in which aspirin was given every other day raised the OR to 0.91 (95% CI 0.74 to 1.11). Reported cancer benefits appeared approximately 5 years from start of treatment. Calculation of absolute effects per 100,000 patient-years of follow-up showed reductions ranging from 33 to 46 deaths (all-cause mortality), 60-84 MCEs and 47-64 incidents of CHD and a possible avoidance of 34 deaths from CRC. Reported increased RRs of adverse events from aspirin use were 37% for GI bleeding (RR 1.37, 95% CI 1.15 to 1.62), between 54% (RR 1.54, 95% CI 1.30 to 1.82) and 62% (RR 1.62, 95% CI 1.31 to 2.00) for major bleeds, and between 32% (RR 1.32, 95% CI 1.00 to 1.74) and 38% (RR 1.38, 95% CI 1.01 to 1.82) for haemorrhagic stroke. Pooled estimates of increased RR for bleeding remained stable across trials conducted over several decades. Estimates of absolute rates of harm from aspirin use, per 100,000 patient-years of follow-up, were 99-178 for non-trivial bleeds, 46-49 for major bleeds, 68-117 for GI bleeds and 8-10 for haemorrhagic stroke. Meta-analyses aimed at judging risk of bleed according to sex and in individuals with diabetes were insufficiently powered for firm conclusions to be drawn. Limitations: Searches were date limited to 2008 because of the intense interest that this subject has generated and the cataloguing of all primary research in so many previous systematic reviews. A further limitation was our potential over-reliance on study-level systematic reviews in which the person-years of follow-up were not accurately ascertainable. However, estimates of number of events averted or incurred through aspirin use calculated from data in study-level meta-analyses did not differ substantially from estimates based on individual patient data-level meta-analyses, for which person-years of follow-up were more accurate (although based on less-than-complete assemblies of currently available primary studies). Conclusions: We have found that there is a fine balance between benefits and risks from regular aspirin use in primary prevention of CVD. Effects on cancer prevention have a long lead time and are at present reliant on post hoc analyses. All absolute effects are relatively small compared with the burden of these diseases. Several potentially relevant ongoing trials will be completed between 2013 and 2019, which may clarify the extent of benefit of aspirin in reducing cancer incidence and mortality. Future research considerations include expanding the use of IPD meta-analysis of RCTs by pooling data from available studies and investigating the impact of different dose regimens on cardiovascular and cancer outcomes