Commissioning for health improvement following the 2012 health and social care reforms in England: what has changed?

BACKGROUND: The wide-ranging program of reforms brought about by the Health and Social Care Act (2012) in England fundamentally changed the operation of the public health system, moving responsibility for the commissioning and delivery of services from the National Health Service to locally elected councils and a new national public health agency. This paper explores the ways in which the reforms have altered public health commissioning. METHODS: We conducted multi-methods research over 33 months, incorporating national surveys of Directors of Public Health and local council elected members at two time-points, and in-depth case studies in five purposively selected geographical areas. RESULTS: Public health commissioning responsibilities have changed and become more fragmented, being split amongst a range of different organisations, most of which were newly created in 2013. There is much change in the way public health commissioning is done, in who is doing it, and in what is commissioned, since the reforms. There is wider consultation on decisions in the local council setting than in the NHS, and elected members now have a strong influence on public health prioritisation. There is more (and different) scrutiny being applied to public health contracts, and most councils have embarked on wide-ranging changes to the health improvement services they commission. Public health money is being used in different ways as councils are adapting to increasing financial constraint. CONCLUSIONS: Our findings suggest that, while some of the intended opportunities to improve population health and create a more joined-up system with clearer leadership have been achieved, fragmentation, dispersed decision-making and uncertainties regarding funding remain significant challenges. There have been profound changes in commissioning processes, with consequences for what health improvement services are ultimately commissioned. Time (and further research) will tell if any of these changes lead to improved population health outcomes and reduced health inequalities, but many of the opportunities brought about by the reforms are threatened by the continued flux in the system.

Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder.

BACKGROUND: Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes. METHOD: Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted. RESULTS: Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN. CONCLUSIONS: This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.

Integration, influence and change in public health: findings from a survey of Directors of Public Health in England.

BACKGROUND: Following the Health and Social Care Act in England, public health teams were formally transferred from the NHS to local authorities in April 2013. METHODS: Online survey of Directors of Public Health (DsPH) in local authorities in England (n = 152) to investigate their experience within local government 1 year on. Tests of association were used to explore relationships between the perceived integration and influence of public health, and changes in how the public health budget was being spent. RESULTS: The organization of and managerial arrangements for public health within councils varied. Most DsPH felt that good relationships had been established within the council, and the move had made them more able to influence priorities for health improvement, even though most felt their influence was limited. Changes in commissioning using the public health budget were already widespread and included the de-commissioning of services. CONCLUSIONS: There was a widespread feeling amongst DsPH that they had greater influence since the reforms, and that this went across the local authority and beyond. Public health's influence was most apparent when the transfer of staff to local government had gone well, when collaborative working relationships had developed, and when local partnership groups were seen as being effective.

Estrogen-related Receptor Alpha (ERRα) is Required for PGC-1α-dependent Gene Expression in the Mouse Brain.

Deficiency in peroxisome proliferator-activated receptor gamma coactivator 1-alpha. (PGC-1α) expression or function is implicated in numerous neurological and psychiatric disorders. PGC-1α is required for the expression of genes involved in synchronous neurotransmitter release, axonal integrity, and metabolism, especially in parvalbumin-positive interneurons. As a transcriptional coactivator, PGC-1α requires transcription factors to specify cell-type-specific gene programs; while much is known about these factors in peripheral tissues, it is unclear if PGC-1α utilizes these same factors in neurons. Here, we identified putative transcription factors controlling PGC-1α-dependent gene expression in the brain using bioinformatics and then validated the role of the top candidate in a knockout mouse model. We transcriptionally profiled cells overexpressing PGC-1α and searched for over-represented binding motifs in the promoters of upregulated genes. Binding sites of the estrogen-related receptor (ERR) family of transcription factors were enriched, and blockade of ERRα attenuated PGC-1α-mediated induction of mitochondrial and synaptic genes in cell culture. Localization in the mouse brain revealed enrichment of ERRα expression in parvalbumin-expressing neurons with tight correlation of expression with PGC-1α across brain regions. In ERRα null mice, PGC-1α-dependent genes were reduced in multiple regions, including neocortex, hippocampus, and cerebellum, though not to the extent observed in PGC-1α null mice. Behavioral assessment revealed ambulatory hyperactivity in response to amphetamine and impairments in sensorimotor gating without the overt motor impairment characteristic of PGC-1α null mice. These data suggest that ERRα is required for normal levels of expression of PGC-1α-dependent genes in neurons but that additional factors may be involved in their regulation.

Causal relations among cell cycle processes in Tetrahymena pyriformis. An analysis employing temperature-sensitive mutants.

Utilization of temperature-sensitive mutants of Tetrahymena pyriformis affected in cell division or developmental pathway selection has permitted elucidation of causal dependencies interrelating micronuclear and macronuclear replication and division, oral development, and cytokinesis. In those mutants in which cell division is specifically blocked at restrictive temperatures, micronuclear division proceeds with somewhat accelerated periodicity but maintains normal coupling to predivision oral development. Macronuclear division is almost totally suppressed in an early acting mutant (mola) that prevents formation of the fission zone, and is variably affected in other mutants (such as mo3) that allow the fission zone to form but arrest constriction. However, macronuclear DNA synthesis can proceed for about four cycles in the nondividing mutant cells. A second class of mutants (psm) undergoes a switch of developmental pathway such that cells fail to enter division but instead repeatedly carry out an unusual type of oral replacement while growing in nutrient medium at the restrictive temperature. Under these circumstances no nuclei divide, yet macronuclear DNA accumulation continues. These results suggest that (a) macronuclear division is stringently affected by restriction of cell division, (b) micronuclear division and replication can continue in cells that are undergoing the type of oral development that is characteristic of division cycles, and (c) macronuclear DNA synthesis can continue in growing cells regardless of their developmental status. The observed relationships among events are consistent with the further suggestion that the cell cycle in this organism may consist of separate clusters of events. with a varying degree of coupling among clusters. A minimal model of the Tetrahymena cell cycle that takes these phenomena into account is suggested.

Analysis of the schedule of DNA replication in heat-synchronized Tetrahymena.

The temporal schedule of DNA replication in heat-synchronized Tetrahymena was studied by autoradiographic and cytofluorometric methods. It was shown that some cells, which were synchronized by selection of individual dividing cells or by temporary thymidine starvation, incorporated [(3)H]thymidine into macronuclei in a periodic fashion during the heat-shock treatment. It was concluded that supernumerary S periods occurred while cell division was blocked by high temperature. The proportion of cells which initiated supernumerary S periods was found to be dependent on the duration of the heat-shock treatment and on the cell cycle stage when the first heat shock was applied. Cytofluorometric measurements of Feulgen-stained macronuclei during the heat-shock treatment indicated that the DNA complement of these cells was substantially increased and probably duplicated during the course of each S period. Estimates of DNA content also suggested that the rate of DNA synthesis progressively declined during long heat-shock treatments. These results indicate that the mechanism which brings about heat-induced division synchrony is not an interruption of the process of DNA replication. Further experiments were concerned with the regulation of DNA synthesis during the first synchronized division cycle. It was shown that participation in DNA synthesis at this time increased as more cells were able to conclude the terminal S period during the preceding heat-shock treatment. It is suggested that a discrete period of time is necessary after the completion of DNA synthesis before another round of DNA synthesis can be initiated.

The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis.

Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and transcription. Here, we report that TOP1MT is overexpressed in cancer tissues and demonstrate that TOP1MT deficiency attenuates tumor growth in human and mouse models of colon and liver cancer. Due to their mitochondrial dysfunction, TOP1MT-KO cells become addicted to glycolysis, which limits synthetic building blocks and energy supply required for the proliferation of cancer cells in a nutrient-deprived tumor microenvironment. Mechanistically, we show that TOP1MT associates with mitoribosomal subunits, ensuring optimal mitochondrial translation and assembly of oxidative phosphorylation complexes that are critical for sustaining tumor growth. The TOP1MT genomic signature profile, based on Top1mt-KO liver cancers, is correlated with enhanced survival of hepatocellular carcinoma patients. Our results highlight the importance of TOP1MT for tumor development, providing a potential rationale to develop TOP1MT-targeted drugs as anticancer therapies.

Considering sex differences clarifies the effects of depression on facial emotion processing during fMRI.

BACKGROUND: Sex differences in emotion processing may play a role in women's increased risk for Major Depressive Disorder (MDD). However, studies of sex differences in brain mechanisms involved in emotion processing in MDD (or interactions of sex and diagnosis) are sparse. METHODS: We conducted an event-related fMRI study examining the interactive and distinct effects of sex and MDD on neural activity during a facial emotion perception task. To minimize effects of current affective state and cumulative disease burden, we studied participants with remitted MDD (rMDD) who were early in the course of the illness. In total, 88 individuals aged 18-23 participated, including 48 with rMDD (32 female) and 40 healthy controls (HC; 25 female). RESULTS: fMRI revealed an interaction between sex and diagnosis for sad and neutral facial expressions in the superior frontal gyrus and left middle temporal gyrus. Results also revealed an interaction of sex with diagnosis in the amygdala. LIMITATIONS: Data was from two sites, which might increase variability, but it also increases power to examine sex by diagnosis interactions. CONCLUSIONS: This study demonstrates the importance of taking sex differences into account when examining potential trait (or scar) mechanisms that could be useful in identifying individuals at-risk for MDD as well as for evaluating potential therapeutic innovations.

Mutations affecting cell division in Tetrahymena pyriformis. I. Selection and genetic analysis.

Fourteen nitrosoguanidine-induced mutations that bring about temperature-sensitive morphological abnormalities resulting from a specific effect on cell division have been isolated as heterozygous phenotypic assortants in Tetrahymena pyriformis syngen 1. Genetic analysis revealed all to be single-gene recessives. Detailed analysis of the kinetics of assortment for one of the mutated alleles revealed a rate (0.0104 pure lines per fission) consistent with that previously observed at other loci in this organism. The mutations fall into six complementation groups (mo1, mo2, mo3, mo6, mo8, and mo12). Homozygotes of mo2 are unconditionally expresed, while all alleles of mo1, mo6, mo8, and mo12 are heat sensitive for division arrest. At the mo3 locus two alleles are heat senstivie, one is primarily cold sensitive, while two are sensitive to both heat and cold. Two out of three combinations of different mo3 alleles show conventional Mendelian segregation of conditions of expression. Different alleles of mo1, mo3, mo8, and mo12 also manifest differences in penetrance at the restrictive temperature. Despite these differences involving expression, the abnormal phenotypes themselves are locus-specific and distinctive; in the one case (mo1a and mo1b) in which two alleles manifest somewhat different phenotypes, the F1 between them is intermediate. One additional recessive mutation (fat1) brings about a nonconditional lengthening of the cell cycle, with some arrest of cell division at the restrictive temperature. These findings demonstrate that selection of heterozygotes undergoing phenotypic assortment can be an effective method for obtaining substantial numbers of a desired class of temperature-sensitive mutations in T. pyriformis.

Clusters within a general adult population of alcohol abstainers.

BACKGROUND: Our previous study found that alcohol abstainers use acute services more and preventative services less than safe level drinkers. The observed relationships between four categories of alcohol consumption and service use were J-shaped for acute services and inverted J-shaped for preventive services. The aim of this paper was to further investigate these relationships. METHODS: The design was a health and lifestyle survey of 41 000 randomly-sampled adults in SE England. The response rate was 60%. Distinctive subgroups within the alcohol abstainer group were investigated using cluster analysis, based on socio-demographic and health status variables. Odds ratios for services use for the abstainer clusters, and three alcohol consumption groups were estimated from a logistic regression model which included age, social class, ethnic group, employment status, household composition, whether the respondent was a carer, smoking habit, use of private health insurance, and health status. RESULTS: Two clusters were formed for both males and females. Cluster 1 comprised, on average, older, frailer, and more disabled people. Cluster 2 comprised younger, healthier people, a greater proportion of whom belonged to ethnic minority groups. Cluster 2 had similar rates of use of Accident & Emergency, GP, optician, and dental services compared with safe level drinkers. Cluster 1's rates differed from those of both Cluster 2 and safe level drinkers in almost all instances. CONCLUSIONS: The J- and inverted J-shaped relationships between alcohol consumption and service use are partly explained by a subgroup of abstainers who are older, of less good health, and who use hospital, clinic, and domiciliary healthcare services much more than safe level drinkers.

The use of acute and preventative medical services by a general population: relationship to alcohol consumption.

AIMS: To investigate the hypothesis that increasing alcohol consumption is accompanied by increasing use of acute, but decreasing use of preventative, medical services among the general population. DESIGN AND PARTICIPANTS: Health and life-style survey of 41,000 randomly-sampled adults in SE England who self-completed a validated questionnaire covering socio-demographics, alcohol and tobacco usage and use of acute (A&E department and general practitioner) and preventative (dental, optician, mammography and cervical cytology) services: the response rate was 60%. MEASUREMENTS: Comparative use of acute and preventative health care services by patients with varying consumption of alcoholic beverages. This was estimated by the odds ratio for service use, after correcting for the following confounding variables; age, social class, ethnic group, employment status, whether lives with children or with other adults, whether is a career, limiting long-term illness, depression status, smoking habit and use of private health insurance. FINDINGS: There was increased use of accident and emergency services by the harmful and intermediate drinking groups compared with the safe drinking group. Male abstainers attended their A&E departments more frequently than 'safe limit' drinkers. With respect to preventative services, both male and female abstainers and harmful drinkers used dental services less than safe limit drinkers. For females, mammography and cervical cytology services were less frequently used by abstainers and by harmful drinkers. CONCLUSIONS: This study supports the generally held view that heavy alcohol consumers are disproportionate users of acute medical services but they are relative under-users of preventative medical care services. Alcohol abstainers are also over-users of acute services, but under-users of preventative services. These latter observations are relevant to the claims that moderate alcohol consumers have lower apparent morbidity and mortality rates compared to abstainers.

Predictors of outcome in patients consulting their general practitioners for headache: a prospective study.

Headache is the most common neurological symptom presenting to general practitioners (GPs). Identifying factors predicting outcome in patients consulting their GPs for headache may help GPs with prognosis and choose management strategies which would improve patient care. We followed up a cohort of patients receiving standard medical care, recruited from 18 general practices in the South Thames region of England, approximately 9 months after their initial participation in the study. Of the baseline sample (N=255), 134 provided both full baseline and follow-up data on measures of interest. We determined associations between patients' follow-up scores on the Headache Impact Test-6 and baseline characteristics (including headache impact and frequency scores, mood, attributions about psychological/medical causes of their headaches, satisfaction with GP care and illness perceptions). Greater impact and stronger beliefs about the negative consequences of headaches at baseline were the strongest predictors of poor outcome at follow-up.

A mutant of Tetrahymena thermophila with a partial mirror-image duplication of cell surface pattern. II. Nature of genic control.

The CU-127 clone of Tetrahymena thermophila, which manifests an unusually high number of ciliary rows plus a second set of abnormal oral structures and of contractile vacuole pores with partial mirror-image reversal of asymmetry (Jerka-Dziadosz & Frankel, 1979), has been subjected to breeding analysis. The progeny ratios obtained in various crosses indicate that the abnormalities of cell-surface asymmetry are brought to expression as a result of the action of a recessive allele at a single gene locus, here named janus. When previously normal cells were made homozygous for the jan allele, the cortical pattern characteristic of the CU-127 clone came rapidly to expression, often without associated change in number of ciliary meridians. Conversely, when cells previously expressing jan re-acquired the wild-type (jan+) allele, they returned to the normal pattern of a single normal oral structure and a single normally located set of contractile vacuole pores while still retaining the high ciliary meridian number characteristic of the original CU-127 clone. The capacity for manifestation of the unique asymmetry pattern depends solely on homozygous expression of the janus allele, whereas the stable number of ciliary meridians in janus clones and the degree of expression of secondary OAs is modulated by other factors, probably at least in part genic. These results, taken together with those of the preceding paper, indicate that the janus allele promotes the propagation and/or expression of a condition of reversed asymmetry in a precisely located cell region, and further indicates that the propagation and expression of this condition are largely independent of the number and asymmetry of ciliary meridians.

Oral ultrastructure and oral development of the misaligned undulating membrane mutant of Tetrahymena thermophila.

The misaligned undulating membrane (mum) mutant of Tetrahymena thermophila is a non-conditional, single gene recessive mutation. The major effect of the mum mutation is the production of multiple undulating membrane (UM) fragments in the oral apparatus (OA). The ultrastructure of the UM fragments of mum OAs is identical to that of the single UM of wild-type OAs. Analysis of OA development at midbody using a combination of light microscopy of protargol-stained cells and SEM of demembranated whole cells showed that the phenotypic effect of the mum mutation first becomes evident during mid to late stage 4 and is fully manifested in early stage 5. The effect of the mutation involves a proliferation of excess basal bodies in the UM field. Subsequent events in the development of the mum OA from mid to late stage 5 are identical to those in wild-type OAs. This study suggests that the mum mutation establishes conditions that allow the production of multiple UMs and thus reveals that the UM field is competent for the complete and coordinated development of several adjacent UMs. This level of regional control is not clearly evident when a single UM is present. The comparison of development of wild-type and mum OAs required an extensive reanalysis of stages 4 and 5 of normal oral development. On the basis of current and previous observations, we propose a new and more subdivided staging system for oral development in Tetrahymena.

Aircraft noise and mental health: II. Use of medicines and health care services.

A domiciliary survey (sample size circa 6000) was conducted in areas of different aircraft noise exposure affected by London (Heathrow) Airport. Respondents were urban dwellers aged 16+. Their use of medicines, general practitioner services, hospital facilities and community services were investigated in relation both to the level of aircraft noise and to the degree of annoyance it causes. None of the indicators showed higher uptake in the high noise areas. The relationships between health indicators, noise and annoyance were not uniform. In areas exposed to high noise the use of non-prescribed drugs was significantly higher among 'very annoyed' than among 'less annoyed' respondents. The uptake of psychotropic drugs, and the use of general practice and out-patient services, tended to increase with increasing annoyance both in high- and low-noise areas, but the differences were not in all cases statistically significant. Parallels were drawn between these results and those of earlier analyses of the same survey related to the prevalence of acute and chronic symptoms. Suggestions for the analysis and interpretation of health effects of noise are put forward.

Non-genic inheritance of cellular handedness.

Ciliates exhibit an asymmetry in arrangement of surface structures around the cell which could be termed handedness. If the usual order of placement of structures defines a 'right-handed' (RH) cell, then a cell with this order reversed would be 'left-handed' (LH). Such LH forms appear to be produced in Tetrahymena thermophila through aberrant reorganization of homopolar doublets back to the singlet condition. Four clones of LH forms were selected and subjected to genetic analysis to test whether this drastic phenotypic alteration resulted from a nuclear genetic change. The results of this analysis indicate that the change in handedness is not due to a genetic change in either the micronucleus or macronucleus. The LH form can, under certain circumstances, revert to the RH form, but typically it propagates itself across both vegetative and sexual generations with similar fidelity. While this analysis does not formally rule out certain possibilities of nuclear genic control involving regulatory elements transmitted through the cytoplasm, when the circumstances of origin and propagation of the LH condition are taken into account direct cortical perpetuation seems far more likely. Here we outline a conceptual framework centred on the idea of longitudinally propagated positional information; the positive evidence supporting this idea as well as further application of the idea itself are presented in the accompanying paper.

Hypoangular: a gene potentially involved in specifying positional information in a ciliate, Tetrahymena thermophila.

In Tetrahymena, two unique cell-surface structures, the oral apparatus and the cytoproct, are formed at opposite ends of one ciliary row, the reference meridian, which is propagated longitudinally during clonal growth. A third set of unique structures, the contractile vacuole pore(s) (CVP), is located at a nearly constant proportion of the cell circumference to the cell's right of the reference meridian. Three allelic recessive temperature-sensitive mutations, collectively named hypoangular (hpo), alter both the geometry of propagation of the reference meridian and the location of the CVPs. In mutant cells, the reference meridian typically undergoes a steady rightward shift in successive cell generations ("cortical slippage"); concomitantly, CVP sets come to lie closer to the reference meridian. Although CVP location is still proportional to the cell circumference, the constant of proportionality (the "CVP angle") is reduced. Another effect is an alteration in the widths of morphogenetic domains within the cortex. As the temperature is raised (made more restrictive), these effects are accentuated and the CVP angle becomes reduced further. At the extreme, the CVP angle collapses to zero and less, i.e., there is a topological switch such that CVPs come to lie to the left of the reference meridian, and the direction of cortical slippage reverses from rightward to leftward. These observations are hard to reconcile with existing formal models of pattern specification in this system and suggest that the hpo locus might specify a key component of the intracellular positional system.

Comparison of three studies of aircraft noise and psychiatric hospital admissions conducted in the same area.

Two earlier studies conducted in the vicinity of London (Heathrow) Airport compared the rate of admissions to a psychiatric hospital from areas exposed to different levels of aircraft noise. Their methods and results were not identical. A third study, reported here, examined standardized rates of admission to the same hospital for a longer period and for a larger area divided into 4 bands of aircraft noise. Statistically significant trends of decreasing admission with increasing noise levels were found. Comparisons between the investigations show how the contradictory results are related to the methods used and the accuracy of the data, and that caution should be exercised in formulating conclusions from exploratory research.

A district screening and treatment service for diabetic retinopathy.

A District Screening and Treatment Service for diabetic retinopathy using diabetic clinic staff is described. From 1978 to 1984 a total of 1195 diabetics entered the screening programme in a district with a population of 136 700. From 1982, when laser treatment became available locally, the average number of patients from the district requiring treatment for the first time per year was 14.0 for proliferative retinopathy and 11.3 for maculopathy. The laser was also used to treat patients from two other districts and the results of treatment from all three districts are reported. Regression of new vessels was achieved in 86% of 72 patients with proliferative retinopathy but 12 of these were also seen at the regional eye centre. Visual acuity was the same or better in 79% of the 104 eyes in 76 patients treated for maculopathy. Effective treatment can be given by a trained hospital practitioner at district level. This reduces demands on the regional centre but good liaison is necessary for difficult cases.