On the role of nerve growth factor in the development of myelinated nociceptors

We have previously demonstrated that administration of antisera against NGF (anti-NGF) can have profound effects on developing primary afferents (Ritter et al., 1991). Chronic administration of anti-NGF to rats beginning on the day of birth results in a severe depletion of cutaneous A delta high-threshold mechanoreceptors (HTMRs) from the sural nerve. Here we have carried out further experiments in order to define the period of time over which this change in the cutaneous afferent population can be produced, and to investigate a possible mechanism for the change. Treatment with anti-NGF from postnatal day (PND) 0-14 resulted in a depletion of cutaneous A delta HTMRs from the sural nerve and also a 20% loss of sensory neurons. However, treatment from PND 2-14 produced an identical deficit of HTMRs without any accompanying cell death. Thus, the depletion of cutaneous A delta HTMRs can be achieved in the absence of cell death induced by anti-NGF treatment. It was also found that a 7 d treatment from PND 4-11 was sufficient to reproduce this effect, but that 7 d treatments earlier (PND 2-9) or later (PND 7-14) within the first 2 weeks were much less effective. This critical period, PND 4-11, corresponds to a period of anatomical change in the innervation of the skin, from epidermal innervation to primarily dermal innervation (Fitzgerald, 1967; Reynolds et al., 1991). In every case where anti-NGF treatment reduced the proportion of HTMRs, there was a reciprocal increase in the proportion of sensitive A delta hair follicle (D-hair) afferents. We hypothesize that in the absence of NGF, developing cutaneous A delta HTMRs do not die but innervate novel targets in the dermis and become D-hair afferents instead

Effect of halo modelling on WIMP exclusion limits

WIMP direct detection experiments are just reaching the sensitivity required to detect galactic dark matter in the form of neutralinos. Data from these experiments are usually analysed under the simplifying assumption that the Milky Way halo is an isothermal sphere with maxwellian velocity distribution. Observations and numerical simulations indicate that galaxy halos are in fact triaxial and anisotropic. Furthermore, in the cold dark matter paradigm galactic halos form via the merger of smaller subhalos, and at least some residual substructure survives. We examine the effect of halo modelling on WIMP exclusion limits, taking into account the detector response. Triaxial and anisotropic halo models, with parameters motivated by observations and numerical simulations, lead to significant changes which are different for different experiments, while if the local WIMP distribution is dominated by small scale clumps then the exclusion limits are changed dramatically.Comment: 9 pages, 9 figures, version to appear in Phys. Rev. D, minor change

We All Know How, Don’t We? On the Role of Scrum in IT-Offshoring

Part 2: Creating Value through Software DevelopmentInternational audienceOffshoring in the IT-industry involves dual interactions between a mother company and an external supplier, often viewed with an implicit perspective from the mother company. This article review general off shoring and IT offshoring literature, focusing on the proliferation of a globally available set of routines; Scrum and Agile. Two cases are studied; a small company and short process and a large mother company with a long process. The interactions of the set ups shows that global concepts like Scrum and Agile are far from a common platform. The “well known” concepts are locally shaped and the enterprises have mixed experiences

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy

GJ 367b: a dense, ultrashort-period sub-Earth planet transiting a nearby red dwarf star

Stars and planetary system