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The Mountain West Clinical and Translational Infrastructure Network Community Engagement and Outreach (CEO) Core has fostered academic-community engagement since 2018. States historically receiving lower levels of NIH funding are characterized by significantly higher proportions of rural and remote populations, as well as uniquely elevated percentages of Native American/Alaska Native and Native Hawaiian/Pacific Islander populations compared to most other states. This case study highlights the Core’s efforts in advancing community-engaged research. Key initiatives included forming a CEO Core Steering Committee to recruit interdisciplinary investigators, establishing regional community advisory boards to identify research priorities, and creating a Resource Library and Training Portal for stakeholders. The Core also collaborated with other Cores to provide training, mentorship, and funding for community-engaged research. Despite these achievements, geographical and cultural diversity presented engagement challenges. Regular meetings between investigators and stakeholders ensured bidirectional communication and aligned goals. The Core transformed transactional engagement into meaningful collaboration, emphasizing the need for interdisciplinary teams who understand community needs. Future goals include training academic teams, clinical providers, and community members, empowering early-stage investigators to share findings with partners, leveraging health records for research, and developing strategies to protect investigators’ time.
Hemoglycin, a space polymer of glycine and iron, has been identified in the carbonaceous chondritic meteorites Allende, Acfer 086, Kaba, Sutter's Mill and Orgueil. Its core form has a mass of 1494 Da and is basically an antiparallel pair of polyglycine strands linked at each end by an iron atom. The polymer forms two- and three- dimensional lattices with an inter-vertex distance of 4.9 nm. Here the extraction technique for meteorites is applied to a 2.1 Gya fossil stromatolite to reveal the presence of hemoglycin by mass spectrometry. Intact ooids from a recent (3000 Ya) stromatolite exhibited the same visible hemoglycin fluorescence in response to x-rays as an intact crystal from the Orgueil meteorite. X-ray analysis confirmed the existence in ooids of an internal three-dimensional lattice of 4.9 nm inter-vertex spacing, matching the spacing of lattices in meteoritic crystals. FTIR measurements of acid-treated ooid and a Sutter's Mill meteoritic crystal both show the presence, via the splitting of the Amide I band, of an extended anti-parallel beta sheet structure. It seems probable that the copious in-fall of carbonaceous meteoritic material, from Archaean times onward, has left traces of hemoglycin in sedimentary carbonates and potentially has influenced ooid formation.
Synthesising knowledge on the health of marine ecosystems and the human activities is crucial to informing holistic marine management. In many coastal states, however, research is conducted in an ad hoc manner and rarely compiled into accessible repositories making it challenging for marine managers to identify knowledge gaps when allocating resources. Here we conduct a structured review of existing literature to identify the current state of marine and coastal knowledge in the Isles of Scilly, an oceanic archipelago in the UK. The archipelago's marine flora and fauna are biogeographically unique in the Northeast Atlantic, with a distinct mosaic of warm and cold temperate habitats and species and are also considered a rare example of a near pristine marine environment in the otherwise highly degraded Northeast Atlantic Ocean. We found 150 sources relating to the marine biodiversity and relevant human activities in the Isles of Scilly with increasing diversification of research topics in recent years. Sources however remain dominated by specific taxa and habitats, suggesting the Isles of Scilly would particularly benefit from future research into: (1) anthropogenic impacts associated with warming waters and intense seasonal vessel activity; (2) development of repeatable survey protocols that can underpin long-term, ecosystem-based monitoring and management (notably for reef and sediment habitats and the European spiny lobster); and (3) data gaps associated with marine teleost fish and elasmobranch communities including identifying core habitat. This review can therefore act as a baseline biological synthesis for the region and importantly, can inform future research priorities.
There is limited data on the organisation of paediatric echocardiography laboratories in Europe.
Methods:
A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs.
Results:
Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1–12), and echocardiography machines was four (range 1–12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20–60) minutes, and for repeat examination was 20 (5–30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%).
Conclusion:
Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Anecdotal evidence suggests the use of bolus tube feeding is increasing in the long-term home enteral tube feed (HETF) patients. A cross-sectional survey to assess the prevalence of bolus tube feeding and to characterise these patients was undertaken. Dietitians from ten centres across the UK collected data on all adult HETF patients on the dietetic caseload receiving bolus tube feeding (n 604, 60 % male, age 58 years). Demographic data, reasons for tube and bolus feeding, tube and equipment types, feeding method and patients’ complete tube feeding regimens were recorded. Over a third of patients receiving HETF used bolus feeding (37 %). Patients were long-term tube fed (4·1 years tube feeding, 3·5 years bolus tube feeding), living at home (71 %) and sedentary (70 %). The majority were head and neck cancer patients (22 %) who were significantly more active (79 %) and lived at home (97 %), while those with cerebral palsy (12 %) were typically younger (age 31 years) but sedentary (94 %). Most patients used bolus feeding as their sole feeding method (46 %), because it was quick and easy to use, as a top-up to oral diet or to mimic mealtimes. Importantly, oral nutritional supplements (ONS) were used for bolus feeding in 85 % of patients, with 51 % of these being compact-style ONS (2·4 kcal (10·0 kJ)/ml, 125 ml). This survey shows that bolus tube feeding is common among UK HETF patients, is used by a wide variety of patient groups and can be adapted to meet the needs of a variety of patients, clinical conditions, nutritional requirements and lifestyles.
Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content.
Aims
To explore syllogism-based rationality in schizophrenia.
Method
Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence and neuropsychological test performance.
Results
Controls outperformed patients on all syllogism types, but the difference between the two groups was only significant for valid syllogisms presented with unusual content. However, when adjusting for intelligence and neuropsychological test performance, all group differences became non-significant.
Conclusions
When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality.
Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)
We tested the hypothesis that energy intake among women with twin pregnancies decreases in late gestation, as the uterus enlarges and they become increasingly uncomfortable. We asked women to recall dietary intake for the previous 24 hours, every 2 weeks from around 29 weeks of gestation, using a photographic atlas and other strategies to estimate portion size. Eighty women provided data at around 29, 31, 33 and 35 weeks of gestation. We calculated total energy intake, and energy intake from carbohydrate, fat and protein. Data were log transformed to reduce skewness. Using mixed effects linear regression models, we found minimal evidence that total energy intake changed over this time period, either before or after adjustment for potential confounding factors (95% confidence interval for relative change per week: −1.4%, 0.6%). There was weak evidence of a small decline in carbohydrate intake over time, both before and after controlling for energy intake. We cannot exclude change in energy intake or diet composition before 29 weeks or after 35 weeks of twin gestation.
Maternal nutrition and growth hormone (GH) treatment during early- to mid-pregnancy can each alter the subsequent growth and differentiation of muscle in progeny. We have investigated the effects of varying maternal nutrition and maternal treatment with porcine (p) GH during the second quarter of pregnancy in gilts on semitendinosus muscle cross-sectional area and fibre composition of progeny, and relationships between maternal and progeny measures and progeny muscularity. Fifty-three Large White×Landrace gilts, pregnant to Large White×Duroc boars, were fed either 2·2 kg (about 35 % ad libitum intake) or 3·0 kg commercial ration (13·5 MJ digestible energy, 150 g crude protein (N×6·25)/kg DM)/d and injected with 0, 4 or 8 mg pGH/d from day 25 to 50 of pregnancy, then all were fed 2·2 kg/d for the remainder of pregnancy. The higher maternal feed allowance from day 25 to 50 of pregnancy increased the densities of total and secondary fibres and the secondary:primary fibre ratio in semitendinosus muscles of their female progeny at 61 d of age postnatally. The densities of secondary and total muscle fibres in semitendinosus muscles of progeny were predicted by maternal weight before treatment and maternal plasma insulin-like growth factor-II during treatment. Maternal pGH treatment from day 25 to day 50 of pregnancy did not alter fibre densities, but increased the cross-sectional area of the semitendinosus muscle; this may be partially explained by increased maternal plasma glucose. Thus, maternal nutrition and pGH treatment during the second quarter of pregnancy in pigs independently alter muscle characteristics in progeny.
Psychological measures have little sensitivity in the prediction of postnatal depression. We report the development of a questionnaire of beliefs about pregnancy and motherhood. Information from a literature review, staff working with women with postnatal depression and interviews with recently ill patients was used to develop a questionnaire called the PRBQ. The PRBQ was piloted on 42 pregnant women and achieved a Cronbach alpha of 0.85. Scores significantly correlated with scores on the Dysfunctional Attitude Scale (DAS), Beck Depression Inventory (BDI) and the Cognitive Adaptation to Stressful Events questionnaire (CASE), measuring adaptation to pregnancy. DAS and CASE scores did not correlate. The PRBQ and the CASE differentiated between those with (n = 5) and those without moderate depression. The PRBQ has been validated against established psychological measures. It may be a helpful tool contributing to the identification of women specifically at risk of postnatal depression. Further basic research is required.
Small size at birth has been associated with increased blood pressure in adult men and women. In rats, isocaloric protein restriction reduces fetal growth and increases systolic blood pressure in adult offspring. Balanced maternal undernutrition in the rat also increases adult blood pressure, but not consistently. The aim of this study was to determine the effect of moderate balanced maternal undernutrition (85% of ad libitum intake from 4 weeks before, and throughout pregnancy) on blood pressure of adult offspring in the guinea pig, a species that is relatively mature at birth. Blood pressure was measured in chronically catheterised offspring of ad libitum fed or feed-restricted mothers, at 3 months of age (young adult). Maternal feed restriction reduced birth weight (−17%) and increased systolic blood pressure (+9%, P < 0.03) in young adult male offspring. In offspring of ad libitum fed and feed-restricted mothers, combined data showed that systolic blood pressure and mean arterial pressure correlated negatively with head width at birth (P = 0.02 and P = 0.04, respectively, n = 28). Systolic blood pressure also correlated negatively with birth weight and the ratio birth weight/birth length, but only in offspring of ad libitum fed mothers (P = 0.04 and P = 0.03, respectively, n = 22). The effect of maternal feed restriction on systolic blood pressure in male offspring was not significant when adjusted for these measures of size at birth. Thus, moderate balanced undernutrition in the guinea pig increases systolic blood pressure in young adult male offspring; however, these effects may be mediated, at least in part, through effects on fetal growth.
Recent studies of the relationship between the apolipoprotein E (APOE) gene and Alzheimer's disease in adults with Down's syndrome have revealed inconsistent results.
Aims
To assess the role of the APOE gene in the manifestation of Alzheimer's disease in adults with Down's syndrome.
Method
We studied the APOE genotypes of 24 adults with dementia and 33 non-demented adults with Down's syndrome over 35 years of age, and an additional group of 164 non-learning disabled adults. We also carried out a meta-analysis of all previously published studies of association between APOE and Down's syndrome, incorporating the current data.
Results
We observed a non-significant excess of APOE ε4 and a reduction of ε2 in adults with dementia compared with non-demented adults with Down's syndrome in our sample. However, meta-analysis showed a significantly higher frequency of ε4 in adults with dementia compared with non-demented adults with Down's syndrome (odds ratio=2.02, 95% CI 1.33–3.07, P=0.001), but no significant reduction in the frequency of ε2.
Conclusions
The APOE ε4 allele acts as a risk factor for the age-specific manifestation of Alzheimer's disease in people with Down's syndrome.
Alzheimer's disease manifests considerable heterogeneity, the cause of which is unknown.
Aims
To determine the familial (genotypic) influence on phenomenology (phenotype) in Alzheimer's disease.
Method
Affected sibling pairs with Alzheimer's disease were assessed for a range of cognitive and non-cognitive symptoms. Resemblance for phenotypic characteristics was estimated using intraclass correlations for continuous traits and by pairwise concordance for dichotomous traits. The relationship between age of onset and APOE genotype was examined using linear regression analysis.
Results
Significant familial effects on age of onset (intraclass correlation 0.41) and mood state (intraclass correlation 0.26), and a relatively high pairwise concordance for agitation (excess concordance 0.1) were found. The APOE locus was found to account for 4% of the variance in age of onset.
Conclusions
Substantial familial influence on age of onset, depression and agitation suggests that genotype does influence phenotype in Alzheimer's disease. Establishing the molecular basis for this phenotypic variation may prove relevant to other neuropsychiatric disorders.
We postulated that chronic placental insufficiency would be associated with reduced expression of renal renin and angiotensinogen genes in the fetal sheep. Placental development was restricted in ewes by removing the majority of caruncles prior to mating (placentally restricted (PR) group). The weights of PR fetuses were significantly reduced (P < 0.05, 2.98 ± 0.33 kg) compared to control fetuses (4.20 ± 0.30 kg). Kidney weights were also significantly reduced in the PR fetuses (P < 0.05, 8.4 ± 0.9 g) compared with control fetuses (12.2 ± 1.3 g). The ratios of renal renin β-actin mRNA levels were significantly reduced in PR fetuses (P < 0.001, 0.35 ± 0.02) when compared to control animals (0.98 ± 0.13). The renal angiotensinogen mRNA/18S rRNA ratio was significantly lower (P < 0.05, 0.28 ± 0.13) in PR fetuses compared with control fetuses (0.72 ± 0.10), while hepatic angiotensinogen was unaffected. There was a positive correlation between renal renin mRNA and renal angiotensinogen mRNA levels (r = 0.65, P < 0.05, n = 12). It is unlikely that these changes in renal angiotensinogen and renin mRNA were due to the small increment in plasma cortisol levels (< 5 nmol l-1). There was, however, a positive correlation between arterial PO2 and renal renin mRNA (r2 = 0.77, P < 0.01). Plasma renin levels were not different between the two groups. Thus, restriction of nutrient and oxygen supply throughout fetal life was associated with suppression of renal renin and renal angiotensinogen gene expression, with no effect on hepatic angiotensinogen mRNA levels. This specific suppression of fetal renal renin and angiotensinogen expression could alter the activity of the intrarenal RAS and so affect growth and development of the kidney.
There is an identified need for more psychiatrists who have been trained in cognitive-behavioural therapy (CBT). The Royal College of Psychiatrists' guidelines for psychotherapy training recommend that all psychiatric trainees receive CBT training. This paper describes a brief programme of CBT training for psychiatric senior house officers (SHO) which demonstrates a viable model achieving limited training objectives.
OPCRIT (a suite of computer programs that allow data entry and generate diagnoses according to 12 operational diagnostic systems) is used in a wide range of psychiatric research including both European Science Foundation and NIMH research initiatives in the molecular genetics of mental disorders. We examined its concurrent validity in 100 subjects collected for linkage studies of Bipolar Disorder and Schizophrenia.
Method
We compared diagnoses generated by OPCRIT from data rated by two trained clinicians with diagnoses made according to consensus, best-estimate, lifetime procedures by the same two raters according to DSM–III–R and RDC classifications.
Results
Good to excellent agreement was achieved between OPCRIT diagnoses and those made by consensus best-estimate procedures.
Conclusions
OPCRIT provides a convenient, reliable, rapid and valid approach to polydiagnostic assessment that can be used as an adjunct to conventional (but time consuming) best-estimate consensus diagnostic procedures.