Self-completed online contact tracing for COVID-19 is associated with reporting fewer contacts: an observational study.

BACKGROUND: Contact tracing was central to England's approach to controlling coronavirus disease 2019 (COVID-19). England's COVID-19 contact tracing system included a step where cases were invited to provide information through an online 'self-service' portal. It is important to understand whether this had any effect on the numbers of contacts reported. METHODS: This study analyses contact tracing data for one local authority in England for 2021. Univariable negative binomial and logistic regression models were used to test for associations between contact tracing tier and average numbers of contacts reported, and key demographic factors and date of reporting. The association between contact tracing tier and number of contacts reported adjusted for age, gender, ethnicity, deprivation and the date on which the case was reported was estimated using a multivariable negative binomial generalized additive regression model with smooth terms for date of reporting and age. RESULTS: Controlling for age, gender, ethnicity, deprivation and date of reporting, self-completed contact tracing was associated with reporting 23% fewer contacts (95% confidence interval 20-25% fewer contacts). CONCLUSION: The use of online self-completed contact tracing may contribute to under-reporting of close contacts. Unmeasured confounding is likely so caution is needed in assuming that the results reflect a causal relationship.

Welfare and well-being: towards mental health-promoting welfare systems.

By protecting vulnerable people from poverty and debt, welfare systems can be powerful tools for promoting mental health. However, the details of how welfare systems are implemented determine whether they also cause harm. Here, we review evidence and principles that might guide the development of mental health-promoting welfare systems.

Using hierarchical clustering to explore patterns of deprivation among English local authorities.

BACKGROUND: The English Indices of Multiple Deprivation (IMD) is widely used as a measure of deprivation. However, similarly ranked areas can differ substantially in the underlying domains of deprivation. These domains contain a richer set of data that might be useful for classifying local authorities. Clustering methods offer a set of techniques to identify groups of areas with similar patterns of deprivation. METHODS: Hierarchical agglomerative (i.e. bottom-up) clustering methods were applied to domain scores for 152 upper tier local authorities. Advances in statistical testing allow clusters to be identified that are unlikely to have arisen from random partitioning of a homogeneous group. The resulting clusters are described in terms of their subdomain scores and basic geographic and demographic characteristics. RESULTS: Five statistically significant clusters of local authorities were identified. These clusters only partially reflect different levels of overall deprivation. In particular, two clusters share similar overall IMD scores but have contrasting patterns of deprivation. CONCLUSION: Hierarchical clustering methods identify five distinct clusters that do not correspond closely to quintiles of deprivation. This approach may help to distinguish between places that face similar underlying challenges, and places that appear similar in terms of overall deprivation scores, but that face different challenges.

Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model.

The pathological end-state of Parkinson disease is well described from postmortem tissue, but there remains a pressing need to define early functional changes to susceptible neurons and circuits. In particular, mechanisms underlying the vulnerability of the dopamine neurons of the substantia nigra pars compacta (SNc) and the importance of protein aggregation in driving the disease process remain to be determined. To better understand the sequence of events occurring in familial and sporadic Parkinson disease, we generated bacterial artificial chromosome transgenic mice (SNCA-OVX) that express wild-type α-synuclein from the complete human SNCA locus at disease-relevant levels and display a transgene expression profile that recapitulates that of endogenous α-synuclein. SNCA-OVX mice display age-dependent loss of nigrostriatal dopamine neurons and motor impairments characteristic of Parkinson disease. This phenotype is preceded by early deficits in dopamine release from terminals in the dorsal, but not ventral, striatum. Such neurotransmission deficits are not seen at either noradrenergic or serotoninergic terminals. Dopamine release deficits are associated with an altered distribution of vesicles in dopaminergic axons in the dorsal striatum. Aged SNCA-OVX mice exhibit reduced firing of SNc dopamine neurons in vivo measured by juxtacellular recording of neurochemically identified neurons. These progressive changes in vulnerable SNc neurons were observed independently of overt protein aggregation, suggesting neurophysiological changes precede, and are not driven by, aggregate formation. This longitudinal phenotyping strategy in SNCA-OVX mice thus provides insights into the region-specific neuronal disturbances preceding and accompanying Parkinson disease.

Region-specific deficits in dopamine, but not norepinephrine, signaling in a novel A30P α-synuclein BAC transgenic mouse.

Parkinson's disease (PD) is a neurodegenerative disorder classically characterized by the death of dopamine (DA) neurons in the substantia nigra pars compacta and by intracellular Lewy bodies composed largely of α-synuclein. Approximately 5-10% of PD patients have a familial form of Parkinsonism, including mutations in α-synuclein. To better understand the cell-type specific role of α-synuclein on DA neurotransmission, and the effects of the disease-associated A30P mutation, we generated and studied a novel transgenic model of PD. We expressed the A30P mutant form of human α-synuclein in a spatially-relevant manner from the 111kb SNCA genomic DNA locus on a bacterial artificial chromosome (BAC) insert on a mouse null (Snca-/-) background. The BAC transgenic mice expressed α-synuclein in tyrosine hydroxylase-positive neurons and expression of either A30P α-synuclein or wildtype α-synuclein restored the sensitivity of DA neurons to MPTP in resistant Snca-/- animals. A30P α-synuclein mice showed no Lewy body-like aggregation, and did not lose catecholamine neurons in substantia nigra or locus coeruleus. However, using cyclic voltammetry at carbon-fiber microelectrodes we identified a deficit in evoked DA release in the caudate putamen, but not in the nucleus accumbens, of SNCA-A30P Snca-/- mice but no changes to release of another catecholamine, norepinephrine (NE), in the NE-rich ventral bed nucleus of stria terminalis. SNCA-A30P Snca-/- mice had no overt behavioral impairments but exhibited a mild increase in wheel-running. In summary, this refined PD mouse model shows that A30P α-synuclein preferentially perturbs the dopaminergic system in the dorsal striatum, reflecting the region-specific change seen in PD.

Suicide rates and suicidal behaviour in displaced people: A systematic review.

BACKGROUND: Refugees, and other forcibly displaced people, face mental distress and may be disproportionately affected by risk factors for suicide. Little is known about suicidal behaviour in these highly mobile populations because collecting timely, relevant, and reliable data is challenging. METHODS AND FINDINGS: A systematic review was performed to identify studies of any design reporting on suicide, suicide attempts, or suicidal ideation among populations of displaced people. A sensitive electronic database search was performed in August 2020, and all retrieved studies were screened for relevance by two authors. Studies were categorised by the population being evaluated: refugees granted asylum, refugees living in temporary camps, asylum seekers, or internally displaced people. We distinguished between whether the sampling procedure in the studies was likely to be representative, or the sample examined a specific non-representative subgroup of displaced people (such as those already diagnosed with mental illness). Data on the rates of suicide or the prevalence of suicide attempts or suicidal ideation were extracted by one reviewer and verified by a second reviewer from each study and converted to common metrics. After screening 4347 articles, 87 reports of 77 unique studies were included. Of these, 53 were studies in representative samples, and 24 were based on samples of specific target populations. Most studies were conducted in high-income countries, and the most studied population subgroup was refugees granted asylum. There was substantial heterogeneity across data sources and measurement instruments utilised. Sample sizes of displaced people ranged from 33 to 196,941 in studies using general samples. Suicide rates varied considerably, from 4 to 290 per 100,000 person-years across studies. Only 8 studies were identified that compared suicide rates with the host population. The prevalence of suicide attempts ranged from 0.14% to 15.1% across all studies and varied according to the prevalence period evaluated. Suicidal ideation prevalence varied from 0.17% to 70.6% across studies. Among refugees granted asylum, there was evidence of a lower risk of suicide compared with the host population in 4 of 5 studies. In contrast, in asylum seekers there was evidence of a higher suicide risk in 2 of 3 studies, and of a higher risk of suicidal ideation among refugees living in camps in 2 of 3 studies compared to host populations. CONCLUSION: While multiple studies overall have been published in the literature on this topic, the evidence base is still sparse for refugees in camps, asylum seekers, and internally displaced people. Less than half of the included studies reported on suicide or suicide attempt outcomes, with most reporting on suicidal ideation. International research networks could usefully define criteria, definitions, and study designs to help standardise and facilitate more research in this important area. REGISTRATION: PROSPERO CRD42019137242.

Perceptions of health and healthcare in ex-Army residents of Tameside: a pilot qualitative study.

BACKGROUND: Local authorities and other service providers need data on their local ex-military communities to be able to plan services. However, published research and data may not be applicable to the local population. Qualitative research offers a relatively low-cost way to get insights into the needs of local ex-military communities. METHODS: A pilot study using in-depth interviews with a small convenience sample of former ex-Army residents of Tameside. Framework analysis was used to identify and group themes arising from the data. This study was conducted using the Consolidated Criteria for Reporting Qualitative Research. RESULTS: While participants saw mental health as a particular challenge, they felt that it tends to get disproportionate attention relative to other needs. The study identified potential barriers to accessing health services that arise from an interaction between aspects of military and civilian healthcare culture and practices. Participants also said that military service could affect the health of both partners and children and that these effects might be more pronounced at key times, such as during adolescence. CONCLUSION: Participants' perceptions of the health of former members of the Armed forces reflect the published epidemiological literature. This suggests that qualitative data can be valid for understanding the health needs of local ex-military communities. Further research is needed to test the findings here with a broader group of ex-military personnel, to explore the barriers faced in accessing healthcare and to understand the health needs of the families of ex-service personnel.

Health needs of ex-military personnel in the UK: a systematic review and qualitative synthesis.

BACKGROUND: Despite all local authorities in England signing up to the Armed Forces Covenant, only a small proportion of Joint Strategic Needs Assessments (JSNAs) include detailed consideration of the health of the local ex-military population. This article supports improvements to JSNAs by systematically reviewing published research for evidence of differences in health between the ex-military population and the general public. METHODS: Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology for qualitative synthesis of mixed study designs. SCOPUS, PubMed and Google Scholar were searched for published research on health outcomes among UK ex-military populations. All study designs were included. RESULTS: 43 studies met the inclusion criteria. Rates of mental illness and hearing loss are higher among ex-military populations compared with the general public, while rates of cancer among ex-military personnel born after 1960 are lower. Despite high rates of hazardous drinking among serving personnel, rates of alcohol-related harm among ex-military populations are no higher than the general public. There is a subpopulation at increased risk of a range of adverse outcomes. This group is variously identified as younger, male, less educated, more likely to have served in a combat role and/or left service early. CONCLUSIONS: This review found evidence of areas of increased and reduced disease burden among ex-military populations. More detailed information on the make-up of the local ex-service population would support more meaningful needs assessments. The Ministry of Defence and local authorities and service providers should work together to support early identification and targeted support for those at the highest risk of adverse outcomes.

Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein.

Alpha-synuclein is intimately involved in the pathogenesis of Parkinson's disease, and has been implicated in the regulation of synthesis, release and reuptake of dopamine (DA). However, mice lacking members of the synuclein family have been reported to display no overt behavioural phenotype. This may be a result of compensatory upregulation of other synucleins during development. Here we report on behaviour and DA synapse function of alpha-synuclein null, gamma-synuclein null, and alpha-gamma-synuclein double-null knockout mice. Double-null mice were hyperactive in a novel environment and alternated at a lower rate in a T-maze spontaneous alternation task, a phenotype reminiscent of mice expressing reduced levels of the DA transporter. To investigate a possible hyperdopaminergic phenotype in alpha-gamma-synuclein double-null mice, we used fast-scan cyclic voltammetry at carbon-fibre microelectrodes to assess DA release and reuptake in striatal slices from wild-type, alpha-null, gamma-null and double-null mice in real time. Double-null mice were found to have a twofold increase in the extracellular concentration of DA detected after discrete electrical stimuli in the striatum. By measuring the rate of reuptake of DA and tissue DA content in these animals, we showed that the observed increase in size of striatal DA transients was not attributable to a decrease in reuptake of DA via the DA transporter, and can not be attributed to an increase in tissue DA levels in the striatum. Rather, we propose that loss of both alpha- and gamma-synuclein causes an increase in release probability from dopaminergic synapses.

Herpes simplex virus type 1 amplicon vectors for the infectious delivery and expression of genomic DNA loci.

A wide range of viral gene transfer technologies has been developed for gene therapy and functional genetic purposes. Different viral vectors vary in transgene capacity, range of infectivity and stability of expression. It is now becoming increasingly apparent that there are distinct advantages in using a complete genomic locus as a transgene to produce physiological levels of tissue-specific, sustained expression. However, the number of vector systems capable of delivering complete genomic loci is limited. The development of the infectious bacterial artificial chromosome system, a herpes simplex virus type 1-based vector that provides efficient infectious delivery and expression of bacterial artificial chromosome or P1-based artificial chromosome clone inserts, is reviewed. This system currently represents the leading technology capable of infectious delivery and expression of complete genomic DNA loci above 100 kb.