Side effects of phenobarbital and carbamazepine in childhood epilepsy: randomised controlled trial

Objective: To compare the behavioural side effects associated with two commonly used antiepilepsy drugs--phenobarbital and carbamazepine--in children in Bangladesh. Design: Prospective randomised controlled single centre trial. Setting: Specialist children's hospital in Dhaka, Bangladesh. Participants: 108 children aged 2-15 with generalised tonic-clonic (n=51) or partial and secondary generalised seizures (n=57). Main outcome measures: Seizure control and behavioural side effects. Results: 91 children were followed up for 12 months. Six required a change of antiepilepsy drug. Side effects were compared in 85 children. In the last quarter of the 12 month follow-up, 71 children were seizure free after one year's treatment. Thirty two in the phenobarbital group and 39 in the carbamazepine group had no seizures in 74 and 102 days after randomisation, respectively. Ten children had increased behavioural problems, which were unacceptable in four (one in the phenobarbital group and three in the carbamazepine group). Independent t tests, however, showed no difference between the two trial drugs. Conclusion: There was no excess in behavioural side effects with phenobarbital in children with epilepsy in a country with limited resources

Investigation of organic matter and biomarkers from Diepkloof Rock Shelter, South Africa: Insights into Middle Stone Age site usage and palaeoclimate

The file associated with this record is under embargo until 36 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.Diepkloof Rock Shelter (DRS) represents a site of major interest for reconstructing early human behaviours during the Middle Stone Age (MSA). Rock shelters such as DRS also potentially preserve information concerning the environmental context for such behaviours. In this respect the organic matter composition of rock shelter sediments has rarely been investigated in detail, particularly at the molecular level. Here, we used pyrolysis-gas chromatography/mass spectrometry (py-GC/MS) to systematically assess the organic matter composition of bulk sediments within the MSA and Later Stone Age (LSA) sequence at DRS. From this we sought to gain insights into site usage, taphonomy and burning practices. Additionally, we analysed the chain length distribution of leaf-wax n-alkanes as well as their hydrogen and carbon isotopic compositions (δDwax and δ13Cwax) to investigate their potential as hydroclimate and vegetation indicators. This constitutes the first leaf-wax isotopic data in a terrestrial context of this antiquity in South Africa. Py-GC/MS shows a dichotomy between stratigraphic units (SUs) of high organic matter content, producing a range of pyrolysis products, including homologous series of long chain n-alkene/n-alkane doublets and alkyl-nitriles, and SUs of low organic matter content, dominated by aromatic, heterocyclic N and polycyclic aromatic hydrocarbon (PAH) pyrolysis products; typical molecular burning products. Several SUs of the Intermediate Howiesons Poort interval exhibit the latter composition, consistent with micromorphological evidence. δ13Cwax remains stable throughout the MSA, but leaf-wax n-alkane chain length and δDwax increase during the Late Howiesons Poort interval. Comparison with such patterns in modern plants in the region suggests this represents a shift towards the input of more arid-adapted vegetation into the shelter, driven either by aridification at the site locale or a change in selection practices. Our results suggest that these techniques have further potential in southern Africa and globally at sites where organic matter preservation is high.Peer-reviewedPost-prin

Storm time polar cap expansion: interplanetary magnetic field clock angle dependence

It is well known that the polar cap, delineated by the open–closed field line boundary (OCB), responds to changes in the interplanetary magnetic field (IMF). In general, the boundary moves equatorward when the IMF turns southward and contracts poleward when the IMF turns northward. However, observations of the OCB are spotty and limited in local time, making more detailed studies of its IMF dependence difficult. Here, we simulate five solar storm periods with the coupled model consisting of the Open Geospace General Circulation Model (OpenGGCM) coupled with the Coupled Thermosphere Ionosphere Model (CTIM) and the Rice Convection Model (RCM), i.e., the OpenGGCM-CTIM-RCM, to estimate the location and dynamics of the OCB. For these events, polar cap boundary location observations are also obtained from Defense Meteorological Satellite Program (DMSP) precipitation spectrograms and compared with the model output. There is a large scatter in the DMSP observations and in the model output. Although the model does not predict the OCB with high fidelity for every observation, it does reproduce the general trend as a function of IMF clock angle. On average, the model overestimates the latitude of the open–closed field line boundary by 1.61∘. Additional analysis of the simulated polar cap boundary dynamics across all local times shows that the MLT of the largest polar cap expansion closely correlates with the IMF clock angle, that the strongest correlation occurs when the IMF is southward, that during strong southward IMF the polar cap shifts sunward, and that the polar cap rapidly contracts at all local times when the IMF turns northward.</p

Chemotherapy-Induced Peripheral Neuropathy: Epidemiology, Pathomechanisms and Treatment

Purpose This review provides an update on the current clinical, epidemiological and pathophysiological evidence alongside the diagnostic, prevention and treatment approach to chemotherapy-induced peripheral neuropathy (CIPN). Findings The incidence of cancer and long-term survival after treatment is increasing. CIPN affects sensory, motor and autonomic nerves and is one of the most common adverse events caused by chemotherapeutic agents, which in severe cases leads to dose reduction or treatment cessation, with increased mortality. The primary classes of chemotherapeutic agents associated with CIPN are platinum-based drugs, taxanes, vinca alkaloids, bortezomib and thalidomide. Platinum agents are the most neurotoxic, with oxaliplatin causing the highest prevalence of CIPN. CIPN can progress from acute to chronic, may deteriorate even after treatment cessation (a phenomenon known as coasting) or only partially attenuate. Different chemotherapeutic agents share both similarities and key differences in pathophysiology and clinical presentation. The diagnosis of CIPN relies heavily on identifying symptoms, with limited objective diagnostic approaches targeting the class of affected nerve fibres. Studies have consistently failed to identify at-risk cohorts, and there are no proven strategies or interventions to prevent or limit the development of CIPN. Furthermore, multiple treatments developed to relieve symptoms and to modify the underlying disease in CIPN have failed. Implications The increasing prevalence of CIPN demands an objective approach to identify at-risk patients in order to prevent or limit progression and effectively alleviate the symptoms associated with CIPN. An evidence base for novel targets and both pharmacological and non-pharmacological treatments is beginning to emerge and has been recognised recently in publications by the American Society of Clinical Oncology and analgesic trial design expert groups such as ACTTION

A gain-of-function sodium channel beta 2-subunit mutation in painful diabetic neuropathy

Diabetes mellitus (DM) is a global challenge with many diverse health sequelae, of which diabetic peripheral neuropathy (DPN) is one of the most common. A substantial number of patients with DPN develop chronic pain, but the genetic and epigenetic factors that predispose DPN patients to develop neuropathic pain are poorly understood. Recent targeted genetic studies have identified mutations in \u3b1-subunits of voltage-gated sodium channels (Navs) in patients with painful DPN. Mutations in proteins that regulate trafficking or functional properties of Navs could expand the spectrum of patients with Nav-related peripheral neuropathies. The auxiliary sodium channel \u3b2-subunits (\u3b21-4) have been reported to increase current density, alter inactivation kinetics, and modulate subcellular localization of Nav. Mutations in \u3b2-subunits have been associated with several diseases, including epilepsy, cancer, and diseases of the cardiac conducting system. However, mutations in \u3b2-subunits have never been shown previously to contribute to neuropathic pain. We report here a patient with painful DPN and negative genetic screening for mutations in SCN9A, SCN10A, and SCN11A-genes encoding sodium channel \u3b1-subunit that have been previously linked to the development of neuropathic pain. Genetic analysis revealed an aspartic acid to asparagine mutation, D109N, in the \u3b22 subunit. Functional analysis using current-clamp revealed that the \u3b22-D109N rendered dorsal root ganglion neurons hyperexcitable, especially in response to repetitive stimulation. Underlying the hyperexcitability induced by the \u3b22 subunit mutation, as evidenced by voltage clamp analysis, we found a depolarizing shift in the voltage-dependence of Nav1.7 fast-inactivation and reduced use-dependent inhibition of the Nav1.7 channel

Centrality dependence of pi^[+/-], K^[+/-], p and p-bar production from sqrt(s_NN)=130 GeV Au + Au collisions at RHIC

Identified pi^[+/-] K^[+/-], p and p-bar transverse momentum spectra at mid-rapidity in sqrt(s_NN)=130 GeV Au-Au collisions were measured by the PHENIX experiment at RHIC as a function of collision centrality. Average transverse momenta increase with the number of participating nucleons in a similar way for all particle species. The multiplicity densities scale faster than the number of participating nucleons. Kaon and nucleon yields per participant increase faster than the pion yields. In central collisions at high transverse momenta (p_T greater than 2 GeV/c), anti-proton and proton yields are comparable to the pion yields.Comment: 6 pages, 3 figures, 1 table, 307 authors, accepted by Phys. Rev. Lett. on 9 April 2002. This version has minor changes made in response to referee Comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Lumos: a statewide linkage programme in Australia integrating general practice data to guide system redesign

ObjectiveWith ageing of the Australian population, more people are living longer and experiencing chronic or complex health conditions. The challenge is to have information that supports the integration of services across the continuum of settings and providers, to deliver person-centred, seamless, efficient and effective healthcare. However, in Australia, data are typically siloed within health settings, precluding a comprehensive view of patient journeys. Here, we describe the establishment of the Lumos programme—the first statewide linked data asset across primary care and other settings in Australia and evaluate its representativeness to the census population.Methods and analysisRecords extracted from general practices throughout New South Wales (NSW), Australia’s most populous state, were linked to patient records from acute and other settings. Innovative privacy and security technologies were employed to facilitate ongoing and regular updates. The marginal demographic distributions of the Lumos cohort were compared with the NSW census population by calculating multiple measures of representation to evaluate its generalisability.ResultsThe first Lumos programme data extraction linked 1.3 million patients’ general practice records to other NSW health system data. This represented 16% of the NSW population. The demographic distribution of patients in Lumos was &gt;95% aligned to that of the NSW population in the calculated measures of representativeness.ConclusionThe Lumos programme delivers an enduring, regularly updated data resource, providing unique insights about statewide, cross-setting healthcare utilisation. General practice patients represented in the Lumos data asset are representative of the NSW population overall. Lumos data can reliably be used to identify at-risk regions and groups, to guide the planning and design of health services and to monitor their impact throughout NSW.</jats:sec

Centrality Dependence of Charged Particle Multiplicity in Au-Au Collisions at sqrt(s_NN)=130 GeV

We present results for the charged-particle multiplicity distribution at mid-rapidity in Au - Au collisions at sqrt(s_NN)=130 GeV measured with the PHENIX detector at RHIC. For the 5% most central collisions we find $dN_{ch}/d\eta_{|\eta=0} = 622 \pm 1 (stat) \pm 41 (syst)$. The results, analyzed as a function of centrality, show a steady rise of the particle density per participating nucleon with centrality.Comment: 307 authors, 43 institutions, 6 pages, 4 figures, 1 table Minor changes to figure labels and text to meet PRL requirements. One author added: M. Hibino of Waseda Universit

Net Charge Fluctuations in Au + Au Interactions at sqrt(s_NN) = 130 GeV

Data from Au + Au interactions at sqrt(s_NN) = 130 GeV, obtained with the PHENIX detector at RHIC, are used to investigate local net charge fluctuations among particles produced near mid-rapidity. According to recent suggestions, such fluctuations may carry information from the Quark Gluon Plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.Comment: 6 pages, RevTeX 3, 3 figures, 307 authors, submitted to Phys. Rev. Lett. on 21 March, 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Flow Measurements via Two-particle Azimuthal Correlations in Au + Au Collisions at sqrt(s_NN) = 130 GeV

Two particle azimuthal correlation functions are presented for charged hadrons produced in Au + Au collisions at RHIC sqrt(s_NN) = 130 GeV. The measurements permit determination of elliptic flow without event-by-event estimation of the reaction plane. The extracted elliptic flow values v_2 show significant sensitivity to both the collision centrality and the transverse momenta of emitted hadrons, suggesting rapid thermalization and relatively strong velocity fields. When scaled by the eccentricity of the collision zone, epsilon, the scaled elliptic flow shows little or no dependence on centrality for charged hadrons with relatively low p_T. A breakdown of this epsilon scaling is observed for charged hadrons with p_T > 1.0 GeV/c for the most central collisions.Comment: 6 pages, RevTeX 3, 4 figures, 307 authors, submitted to Phys. Rev. Lett. on 11 April 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm