The new poor law and county Durham

The thesis traces, in a general sense, the developments that directly led to the legislative reform of a poor relief system that had remained essentially unaltered since its inception too hundred years earlier. The impetus for the dismantling of the Old Poor Law is seen in largely economic terms - the breakdown of a traditional administrative scheme under the pressure of the dramatic fluctuations of an embryonic industrial society. After an extensive review of the provisions of the 1834 Poor Law Amendment Act, the paper turns to a close examination of its implementation in County Durham. The administrative framework erected in the latter 1830’s receives careful attention. An attempt is made to ascertain Poor Law Commission policy and its actual application by local organs. It is found that although the form of poor relief administration was substantially altered by the new measure, in a substantive sense, the economic considerations that animated relief management in previous years continued to dictate, to a large extent, regional administrative practices after the introduction of the Act, despite increasing interference by the Commission

Long-lasting insecticide-treated net usage in eastern Sierra Leone - the success of free distribution.

Summary Objective Médecins Sans Frontières (MSF) runs a malaria control project in Bo and Pujehun districts (population 158 000) that includes the mass distribution, routine delivery and demonstration of correct use of free, long-lasting insecticide-treated nets (LLINs). In 2006/2007, around 65 000 LLINs were distributed. The aim of this follow-up study was to measure LLIN usage and ownership in the project area. Methods Heads of 900 randomly selected households in 30 clusters were interviewed, using a standardized questionnaire, about household use of LLINs. The condition of any LLIN was physically assessed. Results Of the 900 households reported, 83.4% owning at least one LLIN. Of the 16.6% without an LLIN, 91.9% had not participated in the MSF mass distribution. In 94.1% of the households reporting LLINs, the nets were observed hanging correctly over the beds. Of the 1135 hanging LLINs, 75.2% had no holes or 10 or fewer finger-size holes. The most common source of LLINs was MSF (75.2%). Of the 4997 household members, 67.2% reported sleeping under an LLIN the night before the study, including 76.8% of children under 5 years and 73.0% of pregnant women. Conclusion Our results show that MSF achieved good usage with freely distributed LLINs. It is one of the few areas where results almost achieve the new targets set in 2005 by Roll Back Malaria to have at least 80% of pregnant women and children under 5 years using LLINs by 2010

Oxidative stress and the fetotoxicity of alcohol consumption during pregnancy.

Pregnant Quackenbush Special mice were exposed to ethanol under semiacute (3.0 g/kg body weight intragastrically, days 7 to 12 of pregnancy), and chronic conditions (15% ethanol in drinking water for 5 weeks before and during pregnancy) to assess whether embryo-fetotoxic actions of the drug involve oxidative stress effects. Effects were monitored both in the maternal system and embryo. Alcohol compromised the maternal system by increasing the generation of lipid peroxides in the liver. It also decreased glutathione and vitamin E levels, and glutathione peroxidase and superoxide dismutase activities in this organ. Glutathione peroxidase activity in the maternal blood decreased. Only minor alcohol-induced changes occurred in the uterine endometrium, including decreased xanthine oxidase and increased gamma-glutamyl transpeptidase. Similarly, only few changes were induced in day-12 embryos by alcohol. In this case, glutathione content and xanthine oxidase activity decreased while glutathione reductase activity increased following exposure to the chronic regime. With the possible exception of the maternal liver where evidence of oxidative damage was detected, these results do not reflect substantial changes in the antioxidant defences of either the pregnant mouse or embryo. However, the changes may contribute to the growth retarding and other fetotoxic effects of alcohol when they are totalled into the multifactorial actions of the drug

An Emerging Role for the Mammalian Target of Rapamycin in “Pathological” Protein Translation: Relevance to Cocaine Addiction

Complex neuroadaptations within key nodes of the brain’s “reward circuitry” are thought to underpin long-term vulnerability to relapse. A more comprehensive understanding of the molecular and cellular signaling events that subserve relapse vulnerability may lead to pharmacological treatments that could improve treatment outcomes for psychostimulant-addicted individuals. Recent advances in this regard include findings that drug-induced perturbations to neurotrophin, metabotropic glutamate receptor, and dopamine receptor signaling pathways perpetuate plasticity impairments at excitatory glutamatergic synapses on ventral tegmental area and nucleus accumbens neurons. In the context of addiction, much previous work, in terms of downstream effectors to these receptor systems, has centered on the extracellular-regulated MAP kinase signaling pathway. The purpose of the present review is to highlight the evidence of an emerging role for another downstream effector of these addiction-relevant receptor systems – the mammalian target of rapamycin complex 1 (mTORC1). mTORC1 functions to regulate synaptic protein translation and is a potential critical link in our understanding of the neurobiological processes that drive addiction and relapse behavior. The precise cellular and molecular changes that are regulated by mTORC1 and contribute to relapse vulnerability are only just coming to light. Therefore, we aim to highlight evidence that mTORC1 signaling may be dysregulated by drug exposure and that these changes may contribute to aberrant translation of synaptic proteins that appear critical to increased relapse vulnerability, including AMPARs. The importance of understanding the role of this signaling pathway in the development of addiction vulnerability is underscored by the fact that the mTORC1 inhibitor rapamycin reduces drug-seeking in pre-clinical models and preliminary evidence indicating that rapamycin suppresses drug craving in humans

Fluoxetine prevents development of an early stress-related molecular signature in the rat infralimbic medial prefrontal cortex : implications for depression?

Background: Psychological stress, particularly in chronic form, can lead to mood and cognitive dysfunction and is a major risk factor in the development of depressive states. How stress affects the brain to cause psychopathologies is incompletely understood. We sought to characterise potential depression related mechanisms by analysing gene expression and molecular pathways in the infralimbic medial prefrontal cortex (ILmPFC), following a repeated psychological stress paradigm. The ILmPFC is thought to be involved in the processing of emotionally contextual information and in orchestrating the related autonomic responses, and it is one of the brain regions implicated in both stress responses and depression. Results: Genome-wide microarray analysis of gene expression showed sub-chronic restraint stress resulted predominantly in a reduction in transcripts 24 hours after the last stress episode, with 239 genes significantly decreased, while just 24 genes had increased transcript abundance. Molecular pathway analysis using DAVID identified 8 pathways that were significantly enriched in the differentially expressed gene list, with genes belonging to the brain-derived neurotrophic factor – neurotrophin receptor tyrosine kinase 2 (BDNF-Ntrk2) pathway most enriched. Of the three intracellular signalling pathways that are downstream of Ntrk2, real-time quantitative PCR confirmed that only the PI3K-AKT-GSK3B and MAPK/ERK pathways were affected by sub-chronic stress, with the PLCγ pathway unaffected. Interestingly, chronic antidepressant treatment with the selective serotonin reuptake inhibitor, fluoxetine, prevented the stress-induced Ntrk2 and PI3K pathway changes, but it had no effect on the MAPK/ERK pathway. Conclusions: These findings indicate that abnormal BDNF-Ntrk2 signalling may manifest at a relatively early time point, and is consistent with a molecular signature of depression developing well before depression-like behaviours occur. Targeting this pathway prophylactically, particularly in depression-susceptible individuals, may be of therapeutic benefit

High-Grade Copper and Gold Deposited During Postpotassic Chlorite-White Mica-Albite Stage in the Far Southeast Porphyry Deposit, Philippines

Ninety-eight underground diamond holes (~102 km) drilled by Far Southeast Gold Resources Inc. at the Far Southeast porphyry Cu-Au deposit, Philippines, from 2011 to mid-2013, provide a three-dimensional exposure of the deposit between 700- and –750-m elevation, with surface at ~1,400-m elevation. Far Southeast contains an inferred resource of 891.7 million tonnes (Mt) averaging 0.7 g/t Au and 0.5 wt % Cu, equivalent to 19.8 Moz Au and 4.5 Mt Cu. This contribution reports the spatial and temporal distribution of alteration and mineralization at Far Southeast, notably a white-mica–chlorite-albite assemblage that formed after early secondary biotite and before late quartz–white-mica–pyrite alteration and that is associated with the highest copper and gold grades. Alteration assemblages were determined by drill core logging, short-wavelength infrared (SWIR) spectral analysis, petrographic examination, and a quantitative evaluation of materials by scanning electron microscopy (QEMSCAN) study. Alteration is limited around sparse veins or pervasive where vein density is high and the alteration halos coalesce. The alteration and mineralization zones with increasing depth are as follows: (1) the lithocap of quartz-alunite–dominated advanced argillic-silicic alteration that hosts part of the Lepanto high-sulfidation Cu-Au epithermal deposit (mostly above ~700-m elevation), (2) an aluminosilicate-dominated zone with coexisting pyrophyllite-diaspore ± kandite ± alunite and white mica (~700- to ~100-m elevation), (3) porphyry-style assemblages characterized by stockwork veins (below ~500-m elevation), (4) the 1 wt % Cu equivalent ore shell (~400- to –300-m elevation), and (5) an underlying subeconomic zone (about –300- to –750-m elevation, the base of drilling). The ore shells have a typical bell shape centered on a dioritic intrusive complex. The paragenetic sequence of the porphyry deposit includes stage 1 granular gray to white quartz-rich (± anhydrite ± magnetite ± biotite) veins with biotite-magnetite alteration. These were cut by stage 2 lavender-colored euhedral quartz-rich (± anhydrite ± sulfides) veins, with halos of greenish white-mica–chlorite-albite alteration. The white mica is largely illite, with an average 2,203-nm Al-OH wavelength position. The albite may reflect the mafic nature of the diorite magmatism. The quartz veins of this stage are associated with the bulk of copper deposited as chalcopyrite and bornite, as well as gold. Thin Cu sulfide (chalcopyrite, minor bornite) veins with minor quartz and/or anhydrite (paint veins), with or without a white-mica halo, also occur. These veins were followed by stage 3 anhydrite-rich pyrite-quartz veins with white-mica (avg 2,197 nm, illite)–pyrite alteration halos. Combined with previous studies, we conclude that this porphyry system, including the Far Southeast porphyry and Lepanto high-sulfidation Cu-Au deposits, evolved over a period of 0.1–0.2 m.y. Three diorite porphyry stocks were emplaced, and by ~1.4 Ma biotite-magnetite–style alteration formed with quartz-anhydrite veins and deposition of ≤0.5% Cu and ≤0.5 g/t Au (stage 1); coupled with this alteration style, a barren lithocap of residual quartz with quartz-alunite halo plus kandite ± pyrophyllite and/or diaspore formed at shallower depth (>700-m elevation). Subsequently, lavender quartz and anhydrite veins with bornite and chalcopyrite (high-grade stage, avg ~1 wt % Cu and ~1 g/t Au) and white-mica–chlorite-albite halos formed below ~400-m elevation (stage 2). They were accompanied by local pyrite replacement, the formation of hydrothermal breccias and Cu sulfide (paint) veins. Stage 2 was followed at ~1.3 Ma by the formation of igneous breccias largely along the margins of the high-grade zones and stage 3 pyrite-quartz-anhydrite ± chalcopyrite veins with white-mica (mostly illitic) halos. At shallower depths in the transition to the base of the lithocap, cooling led to the formation of aluminosilicate minerals (mainly pyrophyllite ± diaspore ± dickite) with anhydrite plus high-sulfidation-state sulfides and pyrite veinlets. Consistent with previous studies, it is likely that the lithocap-hosted enargite-Au mineralization formed during this later period

BFORE: The B-mode Foreground Experiment

The B-mode Foreground Experiment (BFORE) is a proposed NASA balloon project designed to make optimal use of the sub-orbital platform by concentrating on three dust foreground bands (270, 350, and 600 GHz) that complement ground-based cosmic microwave background (CMB) programs. BFORE will survey ~1/4 of the sky with 1.7 - 3.7 arcminute resolution, enabling precise characterization of the Galactic dust that now limits constraints on inflation from CMB B-mode polarization measurements. In addition, BFORE's combination of frequency coverage, large survey area, and angular resolution enables science far beyond the critical goal of measuring foregrounds. BFORE will constrain the velocities of thousands of galaxy clusters, provide a new window on the cosmic infrared background, and probe magnetic fields in the interstellar medium. We review the BFORE science case, timeline, and instrument design, which is based on a compact off-axis telescope coupled to >10,000 superconducting detectors.Comment: 7 pages, 4 figures, conference proceedings published in Journal of Low Temperature Physic

Adiabatic versus isocurvature non-Gaussianity

We study the extent to which one can distinguish primordial non-Gaussianity (NG) arising from adiabatic and isocurvature perturbations. We make a joint analysis of different NG models based on various inflationary scenarios: local-type and equilateral-type NG from adiabatic perturbations and local-type and quadratic-type NG from isocurvature perturbations together with a foreground contamination by point sources. We separate the Fisher information of the bispectrum of cosmic microwave background temperature and polarization maps by l for the skew spectrum estimator introduced by Munshi and Heavens to study the scale dependence of the signal-to-noise ratio of different NG components and their correlations. We find that the adiabatic and the isocurvature modes are strongly correlated, though the phase difference of acoustic oscillations helps to distinguish them. The correlation between local- and equilateral-type is weak, but the two isocurvature modes are too strongly correlated to be discriminated. Point source contamination, to the extent to which it can be regarded as white noise, can be almost completely separated from the primordial components for l > 100. Including correlations among the different components, we find that the errors of the NG parameters increase by 20-30 per cent for the Wilkinson Microwave Anisotropy Probe 5-year observation, but ~=5 per cent for Planck observations