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Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.
Aims
To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.
Method
Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.
Results
Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).
Conclusions
These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.
This paper examines the population of corporate directors of Britain at the turn of the twentieth century. Over the period 1881-1911 the corporate form became the most common mode of business organisation for large businesses. As their number increased, the population of directors expanded and reflected an increasingly diversified corporate landscape. Based on a large-scale dataset, this paper analyses the characteristics and networks of this wider population of directors. The study goes beyond previous work, which has mainly focused on elite directors or prominent companies, and shows three key findings. First, the population of directors was very connected into a large network, complete isolation from this network was rare. Second, over 1881-1911 director interlocks with banks became less important for most sectors, while interlocks with other financial institutions such as trusts became increasingly important. Insurance companies stood out as the most connected sector spanning smaller local companies and larger international ones. Third, during the period studied there was a shift from director clusters that were mainly based on proximity, to those that were connected through industries.
Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.
Aims
To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.
Method
Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.
Results
Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).
Conclusions
The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.
With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.
With the exponential growth in investment attention to brain health—solutions spanning brain wellness to mental health to neurological disorders—tech giants, payers, and biotechnology companies have been making forays into this field to identify technology solutions and pharmaceutical amplifiers. So far, their investments have had mixed results. The concept of open innovation (OI) was first coined by Henry Chesbrough to describe the paradigm by which enterprises allow free flow of ideas, products, and services from the outside to the inside and vice versa in order to remain competitive, particularly in rapidly evolving fields where there is abundant, relevant knowledge outside the traditional walls of the enterprise. In this article, we advocate for further exploration and advancement of OI in brain health.
Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).
The article links the digital records of individual proprietors in the manuscript censuses 1851–81 for the whole of England and Wales using the BBCE database to identify career changes of employers and own account proprietors. It investigates continuing proprietorship, entry to business from previous activity, and switching out of business. The article identifies the effects on switching of demography, gender, household relationships, sector markets, and opportunity/necessity measured by location and access to railways. Previous analysis of nineteenth-century proprietor careers has been based mainly on local case studies and large firms. This article allows examination across the spectrum of small and large businesses for a representative sample large enough to generalize to the behavior of the whole population. The analysis shows a larger proportion of flows between employer, own account, and worker status than often expected, indicating a relatively open and flexible Victorian economy, and higher than in the modern United Kingdom. Farm and nonfarm activities show contrasted patterns, with farm proprietors more stable with less switching, as to be expected. Switching appears to have slowed slightly over time, with incumbency increasing for both farm and nonfarm employers, and for both men and women, but own account proprietorship was often relatively ephemeral. The article assesses the factors influencing switching using logistic regression. This confirms age, sex, marital status, family position, location, and sector as significant for explaining switching/nonswitching. The results demonstrate that although open and flexible, proprietorship was highly varied between sectors, with changes of railway accessibility mainly significant for farmers.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
This article examines the history of immigrant business proprietors in England and Wales between 1851 and 1911. The newly available electronic version of the Census (I-CeM) allows all business proprietors in each Census year to be identified, and provides birthplace information that allows entrepreneurs from different countries to be compared to each other and to business proprietors born in the United Kingdom. Immigrant populations had higher rates of business proprietorship than the English and Welsh-born population. This article argues that this was caused by labour market structure and demography rather than cultural differences between English- and foreign-born business proprietors.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
Aims
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
Method
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Results
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
Conclusions
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
This article describes the creation of a new urban classification based on the 1891 census of England and Wales. It is the first attempt to use the recently available electronic version of the census (I-CeM) to classify all large towns in late Victorian England and Wales on their economic structure. Where previous scholars were restricted by the form of occupation data contained in the published census reports, I-CeM allows manipulation of the data in order to aggregate urban units and examine their occupational structures in great detail. The classification is then used to compare key socio-economic characteristics of different towns.
The phytotoxicities of soil-incorporated 2,6-dichlorobenzonitrile [dichlobenil] and 2,6-dichlorothiobenzamide [hereinafter referred to as SD-7961] were compared in five soils in the greenhouse. Dichlobenil and SD-7961 were about equally toxic to snap beans (Phaseolus vulgarus L., var. Black Valentine) in each of the five soils. The herbicides were more toxic in Christiana loam than in the other four soils. Phytotoxic residues of both herbicides disappeared most rapidly from Hagerstown silty clay loam and Christiana loam and least rapidly from Sharkey clay. Gas chromatographic analyses of soil extracts confirmed that dichlobenil was most persistent in the clay. Small amounts (0.14 ppmw or less) of 2,6-dichlorobenzoic acid [hereinafter referred to as 2,6-DBA] were detected in soil from greenhouse pot cultures about 9 months after incorporation of dichlobenil. In a field experiment at Beltsville, Maryland, residues of dichlobenil persisted from one season to the next but did not build up in soil sprayed annually for 3 years with 4 or 8 lb/A. Some movement from the surface 6 in into the 6 to 12-in zone occurred on plots sprayed 2 years in succession with 8 lb/A or once with 40 lb/A. Rapid loss of dichlobenil occurred during summer months. When the concentration of dichlobenil on the 40-lb/A plots dropped to about 10%, subsequent loss occurred at a very slow rate.
Farm-to-hospital (FTH) programs can potentially improve the economy of local communities and preserve the environment. Research on adoption of farm-to-hospital (FTH) programs is extremely limited in the agricultural and applied economics literature. Using data from our 2012 regional FTH program survey of hospital food-service directors in the Northeastern United States and from the U.S. Department of Agriculture, this study estimates a logit model to determine factors that influence a hospital's decision to adopt an FTH program. The empirical results indicate that specific hospital characteristics and agricultural factors significantly influence a hospital's decision to adopt.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Syndromic surveillance systems in England have demonstrated utility in the early identification of seasonal gastrointestinal illness (GI) tracking its spatio-temporal distribution and enabling early public health action. There would be additional public health utility if syndromic surveillance systems could detect or track subnational infectious disease outbreaks. To investigate using syndromic surveillance for this purpose we retrospectively identified eight large GI outbreaks between 2009 and 2014 (four randomly and four purposively sampled). We then examined syndromic surveillance information prospectively collected by the Real-time Syndromic Surveillance team within Public Health England for evidence of possible outbreak-related changes. None of the outbreaks were identified contemporaneously and no alerts were made to relevant public health teams. Retrospectively, two of the outbreaks – which happened at similar times and in proximal geographical locations – demonstrated changes in the local trends of relevant syndromic indicators and exhibited a clustering of statistical alarms, but did not warrant alerting local health protection teams. Our suite of syndromic surveillance systems may be more suited to their original purposes than as means of detecting or monitoring localized, subnational GI outbreaks. This should, however, be considered in the context of this study's limitations; further prospective work is needed to fully explore the use of syndromic surveillance for this purpose. Provided geographical coverage is sufficient, syndromic surveillance systems could be able to provide reassurance of no or minor excess healthcare systems usage during localized GI incidents.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
Method
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
Results
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Conclusions
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
We analyze the trajectory of near-Earth asteroid 2009~BD, which is a candidate target of the NASA Asteroid Redirect Mission. The small size of 2009 BD and its Earth-like orbit pose challenges to understanding the dynamical properties of 2009 BD. In particular, nongravitational perturbations, such as solar radiation pressure and the Yarkovsky effect, are essential to match observational data and provide reliable predictions. By using Spitzer Space Telescope IRAC observations and our model for the thermophysical properties and the nongravitational forces acting on 2009 BD we obtain probabilistic derivations of the physical properties of this object. We find two physically possible solutions. The first solution shows 2009 BD as a 2.9 ± 0.3 m diameter rocky body with an extremely high albedo that is covered with regolith-like material, causing it to exhibit a low thermal inertia. The second solution suggests 2009 BD to be a 4 ± 1 m diameter asteroid with albedo 0.45 ± 0.35 that consists of a collection of individual bare rock slabs. We are unable to rule out either solution based on physical reasoning. 2009 BD is the smallest asteroid for which physical properties have been constrained, providing unique information on the physical properties of objects in the size range smaller than 10 m.