Prenatal symptoms of anxiety and depression associated with sex differences in both maternal perceptions of one year old infant temperament and researcher observed infant characteristics.

BACKGROUND: Sex differences in the behaviour of children exposed to prenatal maternal depression and anxiety have been reported. This study compared depression and anxiety symptoms reported by mothers at term with maternal perceptions of one year old male and female infant temperament and with researcher observed infant characteristics, identifying differences for males and females with both approaches. METHODS: Infant behaviour and temperament was assessed via maternally completed questionnaires including Infant Behavioural Questionnaire Revised - Short form and by researcher administered subcomponents of Laboratory Temperament Assessment Battery and Bayley Scales of Infant Development III. RESULTS: For female infants, higher prenatal scores for depression and anxiety were associated with maternal perceptions of lower bonding, higher aggression and negativity, and lower soothability (n = 67 mother-infant dyads). In the laboratory assessment, intensity of escape was the only female infant factor significantly associated with maternal mood (n = 41). For male infants, there was minimal association between prenatal mood scores and maternal perceptions (n = 46) whereas in the laboratory assessment (n = 35) depression scores were associated with expressive language, facial interest and facial fear while anxiety scores were associated with expressive and receptive language, parent behaviour and facial fear. LIMITATIONS: Findings may be restricted to a single ethnicity or mode of delivery. Fewer infants attended the infant assessment. A laboratory setting may mask symptomatology in females. CONCLUSIONS: Atypical maternal perceptions may present a barrier to the early identification of male infants impacted by maternal depression and anxiety.

Author Correction: Egyptian metallic inks on textiles from the 15th century BCE unravelled by non-invasive techniques and chemometric analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products.

Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. In particular, hot-melt extrusion (HME) offers many advantages and has been shown to significantly reduce the number of processing steps relative to a conventional product manufacturing line. To control product quality during HME without process interruption, integration of inline analytical technology is critical. Vibrational spectroscopy (Raman, NIR and FT-IR) is often employed and used for real-time measurements because of the non-destructive and rapid nature of these analytical techniques. However, the establishment of reliable Process Analytical Technology (PAT) tools for HME of thermolabile drugs is challenging. Indeed, the Raman effect is inherently weak and might be subject to interference. Moreover, during HME, heating and photodecomposition can occur and disrupt spectra acquisition. The aim of this research article was to explore the use of inline Raman spectroscopy to characterise a thermolabile drug, ramipril (RMP), during continuous HME processing. Offline measurements by HPLC, LC-MS and Raman spectroscopy were used to characterise RMP and its main degradation product, ramipril-diketopiperazine (RMP-DKP, impurity K). A set of HME experiments together with inline Raman spectroscopic analyses were performed. The feasibility of implementing inline Raman spectroscopic analysis to quantify the level of RMP and RMP-DKP in the extrudate was addressed. Two regions in the Raman spectrum were selected to differentiate RMP and RMP-DKP. When regions were combined, a principle component analysis (PCA) model defined by these two main components (PC 1 = 50.1% and PC 2 = 45%) was established. Using HPLC analyses, we were able to confirm that the PC 1 score was attributed to the level of RMP-DKP, and the PC 2 score was related to the RMP drug content. Investigation of the PCA scatterplot indicated that HME processing temperature was not the only factor causing RMP degradation. Additionally, the plasticiser content, feeding speed and screw rotating speed contributed to RMP degradation during HME processing.

Egyptian metallic inks on textiles from the 15th century BCE unravelled by non-invasive techniques and chemometric analysis.

The development of black inks has enabled writing to become an established method of communication in history. Although a large research effort has been devoted to the study of pigments and dyes used in ancient Egypt to decorate burial walls and furnishings, or to write on papyrus, to date little attention has been paid to the nature and technology of inks used on ritual and daily-use textiles, which may have fostered the transfer of metallic ink technology onto papyrus and parchment supports. We report about inks from 15th century BCE Egyptian textiles by combining non-invasive techniques, including ultraviolet (UV) reflected imaging, near-infrared reflectography (NIRR), X-ray fluorescence (XRF) spectroscopy, Raman spectroscopy and prompt-gamma-activation-analysis (PGAA). It is argued that the inks are related to the family of iron gall inks, whose introduction is commonly attributed to the third century BCE. This interpretation frames the technology of writing on fabrics, used by the ancient Egyptians, in a different time, thus providing new information on the genesis of mordant inks in the ancient Mediterranean cultures. We anticipate our study to be a starting point for further and more sophisticated investigations of textiles, which will clarify the origin of metallic ink in the ancient world.

Exploring the potential of neutron imaging for life sciences on IMAT.

Neutron imaging has been employed in life sciences in recent years and has proven to be a viable technique for studying internal features without compromising integrity and internal structure of samples in addition to being complementary to other methods such as X-ray or magnetic resonance imaging. Within the last decade, a neutron imaging beamline, IMAT, was designed and built at the ISIS Neutron and Muon Source, UK, to meet the increasing demand for neutron imaging applications in various fields spanning from materials engineering to biology. In this paper, we present the first neutron imaging experiments on different biological samples during the scientific commissioning of the IMAT beamline mainly intended to explore the beamline's capabilities and its potential as a noninvasive investigation tool in fields such as agriculture (soil-plants systems), palaeontology and dentistry. LAY DESCRIPTION: Neutrons form a highly penetrating radiation passing through matter without damaging or structurally modifying it, a property that makes them the ideal tool for many kinds of complementary material investigations. Moreover, the strong interaction of neutrons with hydrogen and their ability to distinguish between hydrogen and deuterium with no radiation damage make neutrons a good probe for imaging biological specimens. The recent technological developments of sources and detectors improved the capabilities of neutron imaging instruments and also have facilitated the use of neutron imaging on a much wider scale than before. Neutron imaging is proving its advantages as being complementary to other known methods of investigation such as X-ray imaging or magnetic resonance imaging and it is no surprise that it is not only employed in engineering or archaeology, but also in life sciences. This definitely opens new perspectives for a more interdisciplinary approach in contemporary science. Within the last decade a neutron imaging beamline, IMAT, was designed and built at the ISIS Neutron and Muon Source, UK, to meet the increasing demands of researchers from different fields, spanning from materials engineering to biology. The results presented here, acquired from first measurements on different biological samples during the scientific commissioning of IMAT beamline show the instrument capability and its suitability to palaeontology, agriculture (soil-plants systems) or dentistry applications.

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products.

The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood's apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood's apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples.

Sample environment for neutron scattering measurements of internal stresses in engineering materials in the temperature range of 6 K to 300 K.

Internal stresses in materials have a considerable effect on material properties including strength, fracture toughness, and fatigue resistance. The ENGIN-X beamline is an engineering science facility at ISIS optimized for the measurement of strain and stress using the atomic lattice planes as a strain gauge. Nowadays, the rapidly rising interest in the mechanical properties of engineering materials at low temperatures has been stimulated by the dynamic development of the cryogenic industry and the advanced applications of the superconductor technology. Here we present the design and discuss the test results of a new cryogenic sample environment system for neutron scattering measurements of internal stresses in engineering materials under a load of up to 100 kN and in the temperature range of 6 K to 300 K. Complete cooling of the system starting from the room temperature down to the base temperature takes around 90 min. Understanding of internal stresses in engineering materials at cryogenic temperatures is vital for the modelling and designing of cutting-edge superconducting magnets and other superconductor based applications.

Identification of the novel B*27:144 allele in an Irish Individual.

The sequence of HLA-B*27:144 differs from HLA-B*27:05:02 by one nucleotide change at position 506.

Spread of pedigree versus genetic ancestry in spatially distributed populations.

Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ∼ t rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models.

A review of carbon dioxide monitoring in preterm newborns in the delivery room.

INTRODUCTION: The physiologic adaptation to extra uterine life during the immediate neonatal period is unique. Many newborns require assistance in this adaptive process. Recent evidence now supports titrating oxygen to guide resuscitation but no guidance is provided on utilizing exhaled CO2 measurements. AIM: To review the current evidence relating to the use of CO2 monitoring in preterm newborns in the delivery room. METHODS: Search was performed using the Cochrane Central Register of Controlled Trials, MEDLINE (1966-2014) and PREMEDLINE, EMBASE (1980-2014), CINAHL (1982-2014), Web of Science (1975-2014) and the Oxford Database of Perinatal Trials. RESULTS: The search revealed 21 articles relating to CO2 detection, either quantitative or qualitative, in the newborn infant. The majority of these were observational studies, eight relating to CO2 detection as a means of confirming correct endotracheal tube placement in the newborn infant. The other indication is for mask ventilation, and there is one randomized control trial and four observational studies of CO2 detection during mask ventilation. The overall recommendation for CO2 detection for both clinical uses in the delivery suite is level B. DISCUSSION: CO2 detection may be of particular benefit for preterm infants in the delivery suite. However there is a need for further research into CO2 detection, in particular capnography, as a means of confirming effective PPV in neonatal resuscitation.

Coalescent simulation in continuous space: algorithms for large neighbourhood size.

Many species have an essentially continuous distribution in space, in which there are no natural divisions between randomly mating subpopulations. Yet, the standard approach to modelling these populations is to impose an arbitrary grid of demes, adjusting deme sizes and migration rates in an attempt to capture the important features of the population. Such indirect methods are required because of the failure of the classical models of isolation by distance, which have been shown to have major technical flaws. A recently introduced model of extinction and recolonisation in two dimensions solves these technical problems, and provides a rigorous technical foundation for the study of populations evolving in a spatial continuum. The coalescent process for this model is simply stated, but direct simulation is very inefficient for large neighbourhood sizes. We present efficient and exact algorithms to simulate this coalescent process for arbitrary sample sizes and numbers of loci, and analyse these algorithms in detail.

Beneficence, justice, and health care.

This paper argues that societal duties of health promotion are underwritten (at least in large part) by a principle of beneficence. Further, this principle generates duties of justice that correlate with rights, not merely "imperfect" duties of charity or generosity. To support this argument, I draw on a useful distinction from bioethics and on a somewhat neglected approach to social obligation from political philosophy. The distinction is that between general and specific beneficence; and the approach from political philosophy has at times been called equality of concern. After clarifying the distinction and setting out the basis of the equality of concern view, I argue that the result is a justice-based principle of "specific" beneficence that should be reflected in a society's health policy. I then draw on this account to criticize, refine, and extend some prominent health care policy proposals from the bioethics literature.

Genetic markers of treatment response to tumour necrosis factor-α inhibitors in the treatment of psoriasis.

BACKGROUND: Anti-tumour necrosis factor (TNF)-α therapies have revolutionized the treatment of psoriasis; however, up to 50% of patients do not respond satisfactorily. Identification of pharmacogenetic markers of treatment response is an important stop in the development of individually tailored treatment. The objective of this study was to assess the association of human leucocyte antigen (HLA)-C, killer immunoglobulin receptor (KIR) and vitamin D receptor (VDR) genotypes with response to treatment by etanercept and adalimumab. METHODS: This was a study of 138 patients with severe chronic plaque psoriasis who were treated with etanercept and/or adalimumab. Patients were classified as responders if they achieved a 75% reduction in PASI (PASI75) or were almost clear of psoriasis after 24 weeks of therapy. The frequencies of HLA-C and KIR haplotypes and VDR polymorphisms were compared in responders and nonresponders. The frequency of all HLA-C and KIR genotypes were compared between the 138 patients with psoriasis and 247 healthy donors. RESULTS: The number of patients classified as responders was 46 of 94 (49%) in the etanercept group and 50 of 76 (66%) in the adalimumab group. None of the HLA-C, KIR or VDR genotypes examined was predictive of treatment response. Compared with healthy controls, patients with psoriasis were more likely to have the HLA-C*06 genotype (P < 0.001) and less likely to have the HLA-C*07 genotype (P < 0.001), whereas there was no significant difference in frequencies of any KIR subtype. CONCLUSIONS: Using the candidate gene approach to identify biomarkers of treatment response in psoriasis may have limited utility. This was a small study with limited power. Future larger studies are needed to further examine these findings and to explore alternative approaches to identify predictors of treatment response to biological agents.

Why we should not use the Affordable Care Act to encourage widespread whole genome sequencing.

Perry Payne argues that the health care system should encourage provision of whole genome sequencing (WGS) for most people in the near future. Payne's essay contains two distinct claims. One claim is that near-universal access to WGS would be beneficial both to individuals and to populations who, without it, could be on the losing end of widening health disparities. The second claim is that the preventive services provisions of the Patient Protection and Affordable Care Act (ACA) should be invoked to establish legal entitlements to WGS, without any patient cost sharing. We believe there are strong reasons to reject both of these claims. Indeed, the reasons that count against providing wide access to WGS are the very same reasons that undermine Payne's argument for providing WGS under the preventive services provisions of the ACA.

Real and alleged problems for Daniels's account of health justice.

Norman Daniels's theory of health justice is the most comprehensive and systematic such theory we have. In one of the few articles published so far on Daniels's new book, Just Health, Benjamin Sachs argues that Daniels's core "principle of equality of opportunity does not do the work Daniels needs it to do." Yet Sachs's objections to Daniels's framework are deeply flawed. Where these arguments do not rely on significant misreadings of Daniels, they ignore sensible strands in Just Health that considerably dull their force. After disarming Sachs's arguments against Daniels's theory, I explain why I agree with Sachs's conclusion: Daniels's equality of opportunity-based account of health justice rests on shaky foundations.