Integration and Continuity of Primary Care: Polyclinics and Alternatives, a Patient-Centred Analysis of How Organisation Constrains Care Coordination

Background An ageing population, increasingly specialised of clinical services and diverse healthcare provider ownership make the coordination and continuity of complex care increasingly problematic. The way in which the provision of complex healthcare is coordinated produces – or fails to – six forms of continuity of care (cross-sectional, longitudinal, flexible, access, informational, relational). Care coordination is accomplished by a combination of activities by: patients themselves; provider organisations; care networks coordinating the separate provider organisations; and overall health system governance. This research examines how far organisational integration might promote care coordination at the clinical level. Objectives To examine: 1. What differences the organisational integration of primary care makes, compared with network governance, to horizontal and vertical coordination of care. 2. What difference provider ownership (corporate, partnership, public) makes. 3. How much scope either structure allows for managerial discretion and ‘performance’. 4. Differences between networked and hierarchical governance regarding the continuity and integration of primary care. 5. The implications of the above for managerial practice in primary care. Methods Multiple-methods design combining: 1. Assembly of an analytic framework by non-systematic review. 2. Framework analysis of patients’ experiences of the continuities of care. 3. Systematic comparison of organisational case studies made in the same study sites. 4. A cross-country comparison of care coordination mechanisms found in our NHS study sites with those in publicly owned and managed Swedish polyclinics. 5. Analysis and synthesis of data using an ‘inside-out’ analytic strategy. Study sites included professional partnership, corporate and publicly owned and managed primary care providers, and different configurations of organisational integration or separation of community health services, mental health services, social services and acute in-patient care. Results Starting from data about patients' experiences of the coordination or under-coordination of care we identified: 1. Five care coordination mechanisms present in both the integrated organisations and the care networks. 2. Four main obstacles to care coordination within the integrated organisations, of which two were also present in the care networks. 3. Seven main obstacles to care coordination that were specific to the care networks. 4. Nine care coordination mechanisms present in the integrated organisations. Taking everything into consideration, integrated organisations appeared more favourable to producing continuities of care than were care networks. Network structures demonstrated more flexibility in adding services for small care groups temporarily, but the expansion of integrated organisations had advantages when adding new services on a longer term and larger scale. Ownership differences affected the range of services to which patients had direct access; primary care doctors’ managerial responsibilities (relevant to care coordination because of its impact on GP workload); and the scope for doctors to develop special interests. We found little difference between integrated organisations and care networks in terms of managerial discretion and performance. Conclusions On balance, an integrated organisation seems more likely to favour the development of care coordination, and therefore continuities of care, than a system of care networks. At least four different variants of ownership and management of organisationally integrated primary care providers are practicable in NHS-like settings

The Presence of Flour Affects the Efficacy of Aerosolized Insecticides used to Treat the Red Flour Beetle, Tribolium castaneum

Experiments were conducted in tightly sealed pilot scale warehouses to assess the efficacy of common aerosolized insecticides on all life stages of Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) when exposed in dishes containing 0 to 2 g of wheat flour either under pallets or out in the open. Petri dishes containing 0, 0.1, 1, or 2 g of flour were prepared with 25 eggs, 3rd instars, pupae, or adults and then immediately treated with aerosolized solvent, Pyrethrins, or esfenvalerate. Twenty-four h after insecticide exposure, the dishes were brought to the laboratory and placed in a growth chamber and held for a 3 day moribund (knockdown) assessment and a 21 day mortality assessment. Mortality in untreated controls was generally less than 10%, with the exception of the 21 day counts of adults and eggs. Solvent-treated replications followed similar trends, except that additional mortality was observed in exposed larvae and pupae. In the insecticide-treated dishes, mortality of T. castaneum provisioned with flour generally showed a linear decrease with increasing flour deposits. Regardless of life stage, mortality did not exceed 60% when individuals were exposed in petri dishes containing 2 g of flour. Exposure location also made a significant difference in observed mortality. While mortality never exceeded 75% in dishes positioned under pallets, there was never less than 80% mortality in dishes exposed in the open. Although there was a perceptible increase in mortality with esfenvalerate compared to Pyrethrins, these differences were considerably less than the variation observed among flour deposits. The study suggests that sanitation and preparation prior to aerosol insecticide treatments were more important than choice of a particular insecticide

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Subregional 6-[18F]fluoro-ʟ-m-tyrosine Uptake in the Striatum in Parkinson's Disease

<p>Abstract</p> <p>Background</p> <p>In idiopathic Parkinson's disease (PD) the clinical features are heterogeneous and include different predominant symptoms. The aim of the present study was to determine the relationship between subregional aromatic l-amino acid decarboxylase (AADC) activity in the striatum and the cardinal motor symptoms of PD using high-resolution positron emission tomography (PET) with an AADC tracer, 6-[¹⁸F]fluoro-ʟ-<it>m</it>-tyrosine (FMT).</p> <p>Methods</p> <p>We assessed 101 patients with PD and 19 healthy volunteers. PD was diagnosed based on the UK Brain Bank criteria by two experts on movement disorders. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale (UPDRS). FMT uptake in the subregions of the striatum was analyzed using semi-automated software for region-of-interest demarcation on co-registered magnetic resonance images.</p> <p>Results</p> <p>In all PD patients, FMT uptake was decreased in the posterior putamen regardless of predominant motor symptoms and disease duration. Smaller uptake values were found in the putamen contralateral to the side with more affected limbs. The severity of bradykinesia, rigidity, and axial symptoms was correlated with the decrease of FMT uptake in the putamen, particularly in the anterior part. No significant correlation was observed between tremors and FMT uptake.</p> <p>Conclusions</p> <p>Decrease of FMT uptake in the posterior putamen appears to be most sensitive in mild PD and uptake in the anterior putamen may reflect the severity of main motor symptoms, except for tremor.</p

Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS

Background: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. Methodology/Principal Finding: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn &amp; Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. c-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p,0.001 for pons and p,0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. Conclusion/Significance: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of th

The link between volcanism and plutonism in epizonal magma systems; high-precision U–Pb zircon geochronology from the Organ Mountains caldera and batholith, New Mexico

The Organ Mountains caldera and batholith expose the volcanic and epizonal plutonic record of an Eocene caldera complex. The caldera and batholith are well exposed, and extensive previous mapping and geochemical analyses have suggested a clear link between the volcanic and plutonic sections, making this an ideal location to study magmatic processes associated with caldera volcanism. Here we present high-precision thermal ionization mass spectrometry U–Pb zircon dates from throughout the caldera and batholith, and use these dates to test and improve existing petrogenetic models. The new dates indicate that Eocene volcanic and plutonic rocks in the Organ Mountains formed from ~44 to 34 Ma. The three largest caldera-related tuff units yielded weighted mean [superscript 206]Pb/[superscript 238]U dates of 36.441 ± 0.020 Ma (Cueva Tuff), 36.259 ± 0.016 Ma (Achenback Park tuff), and 36.215 ± 0.016 Ma (Squaw Mountain tuff). An alkali feldspar granite, which is chemically similar to the erupted tuffs, yielded a synchronous weighted mean [superscript 206]Pb/[superscript 238]U date of 36.259 ± 0.021 Ma. Weighted mean [superscript 206]Pb/[superscript 238]U dates from the larger volume syenitic phase of the underlying Organ Needle pluton range from 36.130 ± 0.031 to 36.071 ± 0.012 Ma, and the youngest sample is 144 ± 20 to 188 ± 20 ka younger than the Squaw Mountain and Achenback Park tuffs, respectively. Younger plutonism in the batholith continued through at least 34.051 ± 0.029 Ma. We propose that the Achenback Park tuff, Squaw Mountain tuff, alkali feldspar granite and Organ Needle pluton formed from a single, long-lived magma chamber/mush zone. Early silicic magmas generated by partial melting of the lower crust rose to form an epizonal magma chamber. Underplating of the resulting mush zone led to partial melting and generation of a high-silica alkali feldspar granite cap, which erupted to form the tuffs. The deeper parts of the chamber underwent continued recharge and crystallization for 144 ± 20 ka after the final eruption. Calculated magmatic fluxes for the Organ Needle pluton range from 0.0006 to 0.0030 km3/year, in agreement with estimates from other well-studied plutons. The petrogenetic evolution proposed here may be common to many small-volume silicic volcanic systems

Female responses to experimental removal of sexual selection components in Drosophila melanogaster

Despite the common assumption that multiple mating should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies

The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer

The availability of bromodomain and extra-terminal inhibitors (BETi) has enabled translational epigenetic studies in cancer. BET proteins regulate transcription by selectively recognizing acetylated lysine residues on chromatin. BETi compete with this process leading to both downregulation and upregulation of gene expression. Hypoxia enables progression of triple negative breast cancer (TNBC), the most aggressive form of breast cancer, partly by driving metabolic adaptation, angiogenesis and metastasis through upregulation of hypoxia-regulated genes (for example, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor A (VEGF-A). Responses to hypoxia can be mediated epigenetically, thus we investigated whether BETi JQ1 could impair the TNBC response induced by hypoxia and exert anti-tumour effects. JQ1 significantly modulated 44% of hypoxia-induced genes, of which two-thirds were downregulated including CA9 and VEGF-A. JQ1 prevented HIF binding to the hypoxia response element in CA9 promoter, but did not alter HIF expression or activity, suggesting some HIF targets are BET-dependent. JQ1 reduced TNBC growth in vitro and in vivo and inhibited xenograft vascularization. These findings identify that BETi dually targets angiogenesis and the hypoxic response, an effective combination at reducing tumour growth in preclinical studies