To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Fetal growth restriction (FGR) can be defined as the failure of the fetus to meet its genetically predetermined growth potential  and is associated with significant fetal and perinatal morbidity and mortality. In addition, there is evidence to suggest a longer-term impact of FGR on childhood neurodevelopmental outcomes  and cardiovascular and metabolic diseases that manifest in adulthood . However, predicting FGR is not straightforward and methods for screening and diagnosis are imprecise. In the UK and USA, ultrasound scans in the second half of pregnancy are not performed routinely but targeted at women considered to be at risk for FGR, where high risk is identified by maternal characteristics (including anthropometry and pre-existing disease), the development of complications, or clinical suspicion based on being ‘small for dates’ on physical examination. For practical purposes, FGR may be suspected if biometric measurements are below a given threshold of the distribution in the population, typically <10th, 5th or 3rd centile for gestational age, or if there is a reduction in growth velocity (‘crossing centiles’) from previous scans . The difficulty with using biometry alone is that it does not differentiate between the growth-restricted fetus affected by placental insufficiency, and the healthy, constitutionally small fetus. Therefore, additional measures may be employed to diagnose placental dysfunction, such as Doppler studies of the fetal and uteroplacental circulation, and analysis of maternal serum biomarkers. At present, the only treatment available for FGR is to expedite delivery, but at preterm gestations this can also can cause harm. However, new genomics-based research could help us better understand the etiology of growth restriction and identify more accurate diagnostic biomarkers or potential therapeutic targets. This chapter will focus on current practice in screening for and intervention in FGR and will also consider new developments and the future of the field.
Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity.
We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators.
Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data.
Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.
Understanding the association between diet quality and cardiometabolic risk by education level is important for preventing increased cardiometabolic risk in the Mexican population, especially considering pre-existing disparities in diet quality. The present study examined the cross-sectional association of overall diet quality with cardiometabolic risk, overall and by education level, among Mexican men and women.
Cardiometabolic risk was defined by using biomarkers and diet quality by the Mexican Diet Quality Index. We computed sex-specific multivariable logistic regression models.
Mexican men (n 634) and women (n 875) participating in the Mexican National Health and Nutrition Survey 2012.
We did not find associations of diet quality with cardiometabolic risk factors in the total sample or in men by education level. However, we observed that for each 10-unit increase in the dietary quality score, the odds of diabetes risk in women with no reading/writing skills was 0·47 (95 % CI 0·26, 0·85) relative to the odds in women with ≥10 years of school (referent). Similarly, for each 10-unit increase of the dietary quality score, the odds of having three v. no lipid biomarker level beyond the risk threshold in lower-educated women was 0·27 (95 % CI 0·12, 0·63) relative to the odds in higher-educated women.
Diet quality has a stronger protective association with some cardiometabolic disease risk factors for lower- than higher-educated Mexican women, but no association with cardiometabolic disease risk factors among men. Future research will be needed to understand what diet factors could be influencing the cardiometabolic disease risk disparities in this population.
Phase identification by X-ray diffraction techniques in a complex mixture would be greatly simplified if the component phases could be physically separated. As opposed to current computer search-match algorithms for phase identification, which presuppose a single diffraction scan on a carefully prepared sample, we propose multi-scan data-taking on a not-so-carefully prepared sample so as to exploit certain aberrations in the diffracted intensities. The result can effectively be a physical separation by diffraction. Examples include exploitation of samples having a preferentially oriented component as well as samples with components having differing crystallite sizes. The techniques can involve diffractometer as well as film techniques.
Synchrotron radiation was used to obtain a high-resolution powder diffraction pattern of the high-density form of BeH2, a material whose unit-cell dimensions have not previously been determined. The observed d-spacing values were presented to three different computer indexing programs. All three programs returned as best solution a body-centered orthorhombic unit cell with a = 9.082, b = 4.160, c = 7.707 Å and V = 292 Å3. Interpretation of the three-dimensional Patterson led to 12 BeH2 molecules per unit cell; thus, the theoretical density is 0.755 g/cm3. The molecular structure is based on a network of corner-sharing BeH4 tetrahedra rather than flat, infinite chains with hydrogen bridges previously assumed.
Indexing of powder-diffraction patterns by computer techniques has advanced to the state that it is now often possible to determine unit-cell dimensions and crystal system for an unknown material solely from its powder-diffraction data. This indexing is fully automated, proceeding directly from positions of observed diffraction lines as input, with decision-making steps being made by a computer. Ease of indexing depends on quality of data (accuracy and completeness), volume of the unit cell, and symmetry of the crystal system. In general, a powder pattern of a triclinic compound with a large unit cell requires a more accurate and complete data-set for successful indexing than does a cubic material having a small unit cell. Fortunately, data from a well-aligned diffractometer or Guinier camera ordinarily suffices for computer indexing. Because of systematic errors in the low-lying diffraction lines, data from the Debye-Scherrer technique usually are not adequate for computer indexing (except for the simpler cases). A brief review of the strategies/algorithms of some of the computer indexing codes now available is given. Criteria for assessing the reliability of a particular computer- assisted indexing are discussed. Finally, attention is directed toward future developments such as by automating the collection of powder- diffraction data, analyzing data by computer data processing, and increasing the speed and reliability of computer indexing.
OBJECTIVES/SPECIFIC AIMS: People with metabolically abnormal obesity (MAO), defined as those with insulin resistance and high intrahepatic triglyceride, are at high risk for developing type 2 diabetes and cardiovascular disease. Weight loss through reduced energy intake and increased physical activity has profound impacts on improving cardiometabolic function. However, the specific additional effects of exercise training with diet-induced weight loss on metabolic function are equivocal. METHODS/STUDY POPULATION: A comparative trial is ongoing in MAO adults undergoing 8-10% weight loss induced by a very-low fat plant-based (PB) diet with structured exercise training (n=8) compared to the same weight loss induced by the PB diet alone (n=3). RESULTS/ANTICIPATED RESULTS: Preliminary results indicate that, PB diet with or without exercise training results in significant weight loss concomitant with enhanced insulin sensitivity, reduced intrahepatic triglyceride, reduced 24-hour postprandial glucose response, reduced fat mass, and reduced diastolic blood pressure. Those undergoing PB diet with exercise training had greater improvements in muscular strength and cardiorespiratory fitness than those undergoing PB diet alone. Differences between intervention groups for other cardiometabolic measures are not yet known. DISCUSSION/SIGNIFICANCE OF IMPACT: Each of the interventions resulted in improved cardiometabolic measures; however the extent of the differences between the interventions is not yet clear. It is hypothesized that compared with weight loss induced by a PB diet, the same weight loss induced by a PB diet and structured exercise training will i) cause greater improvement in skeletal muscle insulin sensitivity, ii) will attenuate the usual decline in muscle mass while increasing strength, and iii) result in greater increases in left ventricular diastolic function. The long-term objective of this proposal is to provide a foundation for future studies evaluating mechanisms for the effects of exercise in cardiometabolic disease prevention and therapy.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve difficult decisions particularly about continuing or stopping medications.
To explore what clinical predictors may help to individualise the risk of perinatal recurrence in women with bipolar disorder.
Information was gathered retrospectively by semi-structured interview, questionnaires and case-note review from 887 women with bipolar disorder who have had children. Clinical predictors were selected using backwards stepwise logistic regression, conditional permutation random forests and reinforcement learning trees.
Previous perinatal history of affective psychosis or depression was the most significant predictor of a perinatal recurrence (odds ratio (OR) = 8.5, 95% CI 5.04–14.82 and OR = 3.6, 95% CI 2.55–5.07 respectively) but even parous women with bipolar disorder without a previous perinatal mood episode were at risk following a subsequent pregnancy, with 7% developing postpartum psychosis.
Previous perinatal history of affective psychosis or depression is the most important predictor of perinatal recurrence in women with bipolar disorder and can be used to individualise risk assessments.
To assess the association of fish consumption with risk of dementia and its dose–response relationship, and investigate variations in the association among low-, middle- and high-income countries.
A new community-based cross-sectional study and a systematic literature review.
Urban and rural communities in China; population-based studies systematically searched from worldwide literature.
Chinese adults aged ≥60 years in six provinces (n 6981) took part in a household health survey of dementia prevalence and risk factors. In addition, 33 964 participants from eleven published and eligible studies were included in the systematic review and meta-analysis.
In the new study in China, 326 participants were diagnosed with dementia (4·7 %); those who consumed any amount of fish in the past two years v. those who consumed no fish had reduced risk of dementia (adjusted OR=0·73, 95 % CI 0·64, 0·99), but the dose–response relationship was not statistically significant. The meta-analysis of available data from the literature and the new study showed relative risk (RR) of dementia of 0·80 (95 % CI 0·74, 0·87) for people with fish consumption; the impact was similar among countries with different levels of income. Pooled dose–response data revealed RR (95 % CI) of 0·84 (0·72, 0·98), 0·78 (0·68, 0·90) and 0·77 (0·61, 0·98) in people with low, middle and high consumption of fish, respectively. Corresponding figures for Alzheimer’s disease were 0·88 (0·74, 1·04), 0·79 (0·65, 0·96) and 0·67 (0·58, 0·78), respectively.
Greater consumption of fish is associated with a lower risk of dementia. Increasing fish consumption may help prevent dementia worldwide regardless of income level.
Archaeological investigations of the age and origins of marine shell beads are important for understanding the emergence and maintenance of long-distance trade networks in prehistory. In this paper we expand upon and re-examine the incremental carbon (14C and δ13C) and oxygen (δ18O) isotope data from two Olivella biplicata shell beads from the LSP-1 Rockshelter, Oregon, USA, to address two common problems in dating marine shell trade goods: (1) the source region is large, adding to uncertainty regarding the appropriate specification of ΔR; and (2) the 14C activity within individual specimens is variable. Although this combination of factors severely limits the dating precision that is possible, we recommend a sampling and calibration approach that accounts for these added sources of uncertainty and minimizes the loss of precision. We recommend (1) sequential sampling in order to quantify the range of variability in 14C within shells; (2) a Bayesian calibration procedure that models the 14C dates as an ontogenetic sequence, in this case constrained by stable isotope sclerochronology; and (3) specifying ΔR in a manner that accounts for the full range of possible reservoir offsets in the source region.
Sleep loss may trigger mood episodes in people with bipolar disorder but individual differences could influence vulnerability to this trigger.
To determine whether bipolar subtype (bipolar disorder type I (BP-I) or II (BD-II)) and gender were associated with vulnerability to the sleep loss trigger.
During a semi-structured interview, 3140 individuals (68% women) with bipolar disorder (66% BD-I) reported whether sleep loss had triggered episodes of high or low mood. DSM-IV diagnosis of bipolar subtype was derived from case notes and interview data.
Sleep loss triggering episodes of high mood was associated with female gender (odds ratio (OR) = 143, 95% CI 1.17–1.75, P<0.001) and BD-I subtype (OR=2.81, 95% CI 2.26–3.50, P<0.001). Analyses on sleep loss triggering low mood were not significant following adjustment for confounders.
Gender and bipolar subtype may increase vulnerability to high mood following sleep deprivation. This should be considered in situations where patients encounter sleep disruption, such as shift work and international travel.
Spectral analysis of time series of a c. 17 ± 0.3 year core, calibrated for total ß activity recovered from Sentik Glacier (4908m) Ladakh, Himalaya, yields several recognizable periodicities including subannual, annual, and multi-annual. The time-series, include both chemical data (chloride, sodium, reactive iron, reactive silicate, reactive phosphate, ammonium, δD, δ(18O) and pH) and physical data (density, debris and ice-band locations, and microparticles in size grades 0.50 to 12.70 μm). Source areas for chemical species investigated and general air-mass circulation defined from chemical and physical time-series are discussed to demonstrate the potential of such studies in the development of paleometeorological data sets from remote high-alpine glacierized sites such as the Himalaya.
Social scientific theories frequently posit that multiple causal mechanisms may produce the same outcome. Unfortunately, it is not always possible to observe which mechanism was responsible. For example, IMF scholars conjecture that nations enter IMF agreements both out of economic need and for discretionary domestic political reasons. Typically, though, all we observe is the fact of agreement, not its cause. Partial observability probit models (Poirier 1980, Journal of Econometrics 12:209–217; Braumoeller 2003, Political Analysis 11:209–233) provide one method for the statistical analysis of such phenomena. Unfortunately, they are often plagued by identification and labeling difficulties. Sometimes, however, qualitative studies of particular cases enlighten us about causes when quantitative studies cannot. We propose exploiting this information to lend additional structure to the partial observability approach. Monte Carlo simulation reveals that by anchoring “discernible” causes for a handful of cases about which we possess qualitative information, we obtain greater efficiency. More important, our method proves reliable at recovering unbiased parameter estimates when the partial observability model fails. The paper concludes with an analysis of the determinants of IMF agreements.
A member shall be entitled to purchase the currencies of other members from the Fund …[provided] the member represents that it has a need to make the purchase because of its balance of payments or its reserve position or developments in its reserves.
—International Monetary Fund Articles of Agreement
[IMF] negotiations sometimes enable government leaders to do what they privately wish to do, but are powerless to do domestically.