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Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population.
Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration.
Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009.
Women were recruited when presenting for prenatal care in the early second trimester.
In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration.
We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.
Infrared (IR) spectroscopy is increasingly being used to probe the secondary structure of proteins, especially for high-concentration samples and biopharmaceuticals in complex formulation vehicles. However, the small path lengths required for aqueous protein transmission experiments, due to high water absorbance in the amide I region of the spectrum, means that the path length is not accurately known, so only the shape of the band is ever considered. This throws away a dimension of information. Attenuated total reflectance (ATR) IR spectroscopy is much easier to implement than transmission IR spectroscopy and, for a given instrument and sample, gives reproducible spectra. However, the ATR-absorbance spectrum varies with sample concentration and instrument configuration, and its wavenumber dependence differs significantly from that observed in transmission spectroscopy. In this paper, we determine, for the first time, how to transform water and aqueous protein ATR spectra into the corresponding transmission spectra with appropriate spectral shapes and intensities. The approach is illustrated by application to water, concanavalin A, haemoglobin and lysozyme. The transformation is only as good as the available water refractive index data. A hybrid of literature data provides the best results. The transformation also allows the angle of incidence of an ATR crystal to be determined. This opens the way to using both spectral shape and spectra intensity for protein structure fitting.
Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance.
Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass).
Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition.
Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.
The relationship between depression and sexual behaviour among men who have sex with men (MSM) is poorly understood.
To investigate prevalence and correlates of depressive symptoms (Patient Health Questionnaire-9 score ≥10) and the relationship between depressive symptoms and sexual behaviour among MSM reporting recent sex.
The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary medicine clinic attendees without diagnosed HIV (2013–2014).
Among 1340 MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic disadvantage and lower supportive network. Adjusted for key sociodemographic factors, depressive symptoms were associated with measures of condomless sex partners in the past 3 months (≥2 (prevalence ratio (PR) 1.42, 95% CI 1.17–1.74; P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20–1.71; P<0.001)), sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19–1.79; P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33–2.50; P<0.001).
Management of mental health may play a role in HIV and STI prevention.
Childhood adversity predicts adolescent suicidal ideation but there are few studies examining whether the risk of childhood adversity extends to suicidal ideation in midlife. We hypothesized that childhood adversity predicts midlife suicidal ideation and this is partially mediated by adolescent internalizing disorders, externalizing disorders and adult exposure to life events and interpersonal difficulties.
At 45 years, 9377 women and men from the UK 1958 British Birth Cohort Study participated in a clinical survey. Childhood adversity was prospectively assessed at the ages of 7, 11 and 16 years. Suicidal ideation at midlife was assessed by the depressive ideas subscale of the Revised Clinical Interview Schedule. Internalizing and externalizing disorders were measured by the Rutter scales at 16 years. Life events, periods of unemployment, partnership separations and alcohol dependence were measured through adulthood.
Illness in the household, paternal absence, institutional care, parental divorce and retrospective reports of parental physical and sexual abuse predicted suicidal ideation at 45 years. Three or more childhood adversities were associated with suicidal ideation at 45 years [odds ratio (OR) 4.31, 95% confidence interval (CI) 2.67–6.94]. Psychological distress at 16 years partially mediated the associations of physical abuse (OR 3.41, 95% CI 2.29–5.75), sexual abuse (OR 4.99, 95% CI 2.90–11.16) with suicidal ideation. Adult life events partially mediated the association of parental divorce (OR 6.34, 95% CI −7.16 to 36.75) and physical (OR 9.59, 95% CI 4.97–27.88) and sexual abuse (OR 6.59, 95% CI 2.40–38.36) with suicidal ideation at 45 years.
Adversity in childhood predicts suicidal ideation in midlife, partially mediated by adolescent internalizing and externalizing disorders, adult life events and interpersonal difficulties. Understanding the pathways from adversity to suicidal ideation can inform suicide prevention and the targeting of preventive interventions.
This book presents a wide range of new research on many aspects of naval strategy in the early modern and modern periods. Among the themes covered are the problems of naval manpower, the nature of naval leadership and naval officers, intelligence, naval training and education, and strategic thinking and planning. The book is notable for giving extensive consideration to navies other than those ofBritain, its empire and the United States. It explores a number of fascinating subjects including how financial difficulties frustrated the attempts by Louis XIV's ministers to build a strong navy; how the absence of centralised power in the Dutch Republic had important consequences for Dutch naval power; how Hitler's relationship with his admirals severely affected German naval strategy during the Second World War; and many more besides. The book is a Festschrift in honour of John B. Hattendorf, for more than thirty years Ernest J. King Professor of Maritime History at the US Naval War College and an influential figure in naval affairs worldwide.
N.A.M. Rodger is Senior Research Fellow at All Souls College, Oxford.
J. Ross Dancy is Assistant Professor of Military History at Sam Houston State University.
Benjamin Darnell is a D.Phil. candidate at New College, Oxford.
Evan Wilson is Caird Senior Research Fellow at the National Maritime Museum, Greenwich.
Contributors: Tim Benbow, Peter John Brobst, Jaap R. Bruijn, Olivier Chaline, J. Ross Dancy, Benjamin Darnell, James Goldrick, Agustín Guimerá, Paul Kennedy, Keizo Kitagawa, Roger Knight, Andrew D. Lambert, George C. Peden, Carla Rahn Phillips, Werner Rahn, Paul M. Ramsey, Duncan Redford, N.A.M. Rodger, Jakob Seerup, Matthew S. Seligmann, Geoffrey Till, Evan Wilson
To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women.
A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual.
The Ottawa Hospital and Kingston General Hospital, Ontario, Canada.
Pregnant women recruited between 12 and 20 weeks of gestation.
A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited.
BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.
Necessary and sufficient conditions are given for the existence of a graph decomposition of the Kneser Graph
and of the Generalized Kneser Graph
into paths of length three.
Poly(N-isopropylacrylamide) (PNIPAM) is a thermosensitive polymer that is well-known for its behavior at a lower critical solution temperature (LCST) around 305 K. Below the LCST, PNIPAM is soluble in water, and above this temperature, polymer chains collapse and transform into a globule state. The conformational dynamics of single chains of polymer in a solution is known to be different from those of grafted structures that comprise of an ensemble of such single chains. In this study, we have carried out MD simulations of a mesoscopic nanostructure of PNIPAM polymer chains consisting of 60 monomer units grafted onto gold nanoparticles of different diameters, to study the effect of temperature and core particle size on the polymer conformations. Additionally, we have also studied the effect of grafting density on the coil-to-globule transition exhibited by PNIPAM through the LCST. The systems investigated consisted of ∼3 and ∼6 million atoms. Simulations were carried out below and above the LCST of PNIPAM, at 275K and 325K. Simulation trajectories were analyzed for radius of gyration of PNIPAM chains.
In this work, we take advantage of injection molding as a high volume and repeatable method to create surface areas for the growth of human mesenchymal stem cells (hMSCs). Ultraviolet lithography, combined with deep reactive ion etching, was used to generate micro-features over a relatively large surface area of a silicon wafer. The micro-featured silicon wafer was used as a mold insert for the micro-injection molding process to create polystyrene and low density polyethylene surfaces. Micro-geometry was used to alter the effective surface stiffness of the polymer substrate. Created samples were characterized via scanning electron microscopy and tensile testing. hMSCs were seeded onto samples for initial studies. Actin and vinculin were visualized through ICC to compare cytoskeletal elements. Changes in cell morphology were examined using ICC. Results indicate that injection molding of microfeatured substrates is a viable technique to produce surfaces amenable to stem cell growth.