Exploring rural Scottish GPs' migration decisions: a secondary qualitative analysis considering burnout.

Background: The challenges of recruiting and retaining rural GPs are well described. UK data suggests high levels of burnout, characterised by detachment, exhaustion and cynicism, plays a role in GP turnover. The contrast is engagement with work.

Morphology and vocalization comparison of the Houston Toad and the Dwarf American Toad: implications for their historic range.

Documenting changes in the distribution and abundance of a given taxon requires historical data. In the absence of long-term monitoring data collected throughout the range of a taxon, conservation biologists often rely on preserved museum specimens to determine the past or present, putative geographic distribution. Distributional data for the Houston Toad () has consistently been confounded by similarities with a sympatric congener, the Dwarf American Toad (), both in monitoring data derived from chorusing surveys, and in historical data via museum specimens.

Rurality, healthcare and crises: Investigating experiences, differences, and changes to medical care for people living in rural areas.

Healthcare provision in rural areas is a global challenge, characterised by a dispersed patient population, difficulties in the recruitment and retention of healthcare professionals and a physical distance from hospital care. This research brings together both public and doctor perspectives to explore the experience of healthcare across rural Scotland, against the backdrop of contemporary crises, including a global pandemic and extreme weather events. We draw on two studies on rural healthcare provision to understand how healthcare services have been experienced, changed and might move on after periods of short- and longer-term change caused by such crises.

The impact of travel time to cancer treatment centre on post-diagnosis care and mortality among cancer patients in Scotland.

Limited data exist on the effect of travelling time on post-diagnosis cancer care and mortality. We analysed the impact of travel time to cancer treatment centre on secondary care contact time and one-year mortality using a data-linkage study in Scotland with 17369 patients. Patients with longer travelling time and island-dwellers had increased incidence rate of secondary care cancer contact time.

Valuing place in doctors' decisions to work in remote and rural locations.

Recruitment and retention of medical practitioners is a challenging contemporary issue for rural and remote areas. In this paper, we explore the importance of what it is that doctors value in rural and remote places from their own personal, organisational, social and spatial lives. We do this by drawing on original research from Scotland that explored doctors' decisions on choosing, or not, to work in remote and rural locations.

Predicting surface abundance of federally threatened Jollyville Plateau Salamanders () to inform management activities at a highly modified urban spring.

Urban expansion has contributed to the loss of habitat for range restricted species across the globe. Managing wildlife populations within these urban settings presents the challenge of balancing human and wildlife needs. Jollyville Plateau Salamanders () are a range restricted, federally threatened, species of neotenic brook salamander endemic to central Texas.

Optimizing the power of human performed audio surveys for monitoring the endangered Houston toad using automated recording devices.

Knowledge regarding the locations of populations of endangered species is a critical part of recovery and facilitates land use planning that avoids unnecessary impacts. Regulatory agencies often support the development of survey guidelines designed to standardize the methods and maximize the probability of detection, thereby avoiding incorrectly concluding a species is absent from a site. Here, using simulations with data collected using automated recording devices (ARDs) we evaluated the efficacy of the existing U.

Observer-free experimental evaluation of habitat and distance effects on the detection of anuran and bird vocalizations.

Acoustic surveys of vocalizing animals are conducted to determine density, distribution, and diversity. Acoustic surveys are traditionally performed by human listeners, but automated recording devices (ARD) are becoming increasingly popular. Signal strength decays, or attenuates, with increasing distance between source and receiver and some habitat types may differentially increase attenuation beyond the effects of distance alone.

Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin.

Hyperbilirubinemia is so common in newborns as to be termed physiological. The most common bacteria involved in early-onset neonatal sepsis are Streptococcus agalactiae, commonly called Group B Streptococcus (GBS). Whilst previous studies show bilirubin has antioxidant properties and is beneficial in endotoxic shock, little thought has been given to whether bilirubin might have antibacterial properties.

Prolonged prostaglandin-E2-associated periosteal reaction and elevated C-reactive protein levels.

This is a case review of two infants who received a prolonged course of prostaglandin-E2 therapy for congenital cardiac lesions while awaiting corrective surgery. These cases highlight an association between prolonged prostaglandin-E2 therapy with periosteal reactions and elevated C-reactive protein levels. Failure to recognise this association may lead to multiple courses of antibiotics for presumed sepsis and further prolongation of prostaglandin-E2 therapy.

A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results.

Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3-0·5 mg/m ) was administered over 2 h on days 1, 4, 8, 11; POM (3-4 mg) on days 1-21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle.

Marizomib for central nervous system-multiple myeloma.

Marizomib, a natural marine product, is an irreversible proteasome inhibitor currently under investigation in relapsed-refractory multiple myeloma (RRMM) and malignant glioma. Central nervous system-multiple myeloma (CNS-MM) is a rare manifestation of extra-medullary disease with few therapeutic options, highlighting the unmet clinical need in these patients. Marizomib demonstrated encouraging activity in RRMM and has emerging clinical activity in glioma, making it a potential CNS-MM therapeutic intervention.

Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier.

Background: The proteasome plays a vital role in the physiology of glioblastoma (GBM), and proteasome inhibition can be used as a strategy for treating GBM. Marizomib is a second-generation, irreversible proteasome inhibitor with a more lipophilic structure that suggests the potential for penetrating the blood-brain barrier. While bortezomib and carfilzomib, the 2 proteasome inhibitors approved for treatment of multiple myeloma, have little activity against malignant gliomas in vivo, marizomib could be a novel therapeutic strategy for primary brain tumors.

Nasal CPAP and preterm bradycardia: cause or cure.

Nasal continuous positive airway pressure (nCPAP) is widely used for the treatment of respiratory distress syndrome and apnoea of prematurity. Complications related to fixation devices have been well documented. We report a clinically well preterm baby suffering intermittent, profound episodes of bradycardia without any prior associated apnoea or desaturation.

Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation.

Natural helper (NH) cells are innate lymphoid cells (ILCs) that produce T helper-2 (Th2)-cell-type cytokines in the lung- and gut-associated lymphoid tissues. Currently, the lineage relationship between NH cells in different tissues and between NH cells and interleukin-22 (IL-22)-producing retinoic-acid-receptor-related orphan receptor (ROR)γt-positive ILCs is unclear. Here, we report that NH cells express RORα, but not RORγt.

Chk2 protects against radiation-induced genomic instability.

The murine Chk2 kinase is activated after exposure to ionizing radiation and is necessary for p53-dependent apoptosis, but the role Chk2 plays in determining genomic stability is poorly understood. By analyzing the sensitivity of Chk2-deficient murine and human cells to a range of DNA-damaging agents, we show that Chk2 deficiency results in resistance to agents that generate double-strand breaks but not to other forms of damage. Surprisingly, the absence of Chk2 results in increased sensitivity to UV-radiation-induced DNA damage.

Professional opinions of the use of telemedicine in child & adolescent psychiatry.

The Telemedicine project at Yorkhill Hospital, Glasgow was set up in 2004 to aid in the rapid diagnosis of children at a distant location. The Child and Adolescent Mental Health Services (CAMHS) are now the largest users. CAMHS use this service for clinical work, service development and to aid research.

The impact of diffuseness of coronary artery disease on the outcomes of patients undergoing primary and reoperative coronary artery bypass grafting.

Objective: Diffuse coronary artery disease jeopardizes myocardium, increasing surgical mortality in primary coronary artery bypass grafting (CABG). We sought to determine the impact of diffuseness on pre- and post-discharge outcomes for both primary and reoperative CABG (REOP).

Methods: Using a validated system for measuring diffuseness of coronary disease, preoperative angiograms were scored for primary CABG (n=792) and REOP cases (n=268) performed 1997-2004.

Aspects of the early moments of interaction between tachyzoites of Toxoplasma gondii with neutrophils.

The interaction of the tachyzoite stage of Toxoplasma gondii with neutrophils was investigated. Morphological aspects of the initial moments of interaction were analyzed by transmission and scanning electron microscopy, revealing at least three types of reaction from the leukocytes to the parasite: the projection of filopodia, formation of a tunnel-like projection involving the parasite, and invagination of the leukocyte surface at the point of entry. The influence on infectivity of tyrosine kinase, phosphokinase C and phosphatidylinositol 3 kinase cell signaling pathways were studied with the aid of drugs affecting these enzymes in these cells.

c-Jun-deficient cells undergo premature senescence as a result of spontaneous DNA damage accumulation.

Mouse embryo fibroblasts deficient for the c-Jun proto-oncogene (c-Jun-/- MEF) undergo p53-dependent premature senescence in conventional culture. This phenotype becomes evident only after several cell divisions, suggesting that senescence may result from exposure to unknown environmental factors. Here, we show that c-Jun-/- MEF can proliferate successfully in low oxygen (3% O2), indicating that premature senescence under conventional culture conditions is a consequence of hyperoxic stress.

v-Jun stimulates both cdk2 kinase activity and G1/S progression via transcriptional repression of p21 CIP1.

Previous studies have shown that the viral Jun (v-Jun) oncoprotein induces marked alterations in cell cycle control, which are associated with, and may be caused by, increased cdk2 kinase activity. Since p21 CIP1 is an important regulator of cdk2, we investigated whether aberrant expression of this cyclin-dependent kinase inhibitor might contribute to cell cycle deregulation by v-Jun. We find that the basal levels of p21 CIP1 mRNA and protein expression are greatly reduced in chick embryo fibroblasts (CEF) transformed by v-Jun, and that v-Jun blocks the increases in p21 CIP1 expression that normally accompany growth inhibition induced by serum deprivation or confluency in untransformed CEF.

Cell transformation by v-Jun deactivates ERK MAP kinase signalling.

Previous studies have shown that v-Jun accelerates G1 progression and enables cells to sustain S phase entry in the absence of serum growth factors. Since growth factor-dependent ERK MAP kinase signalling plays an important role in regulating the G1/S transition, we investigated whether aberrant ERK regulation might contribute to cell cycle deregulation by v-Jun. Contrary to expectation, we find that cells transformed by v-Jun exhibit a profound reduction in the basal level of active, dual-phosphorylated ERK.

Further studies on the interaction of Toxoplasma gondii with neutrophils and eosinophils.

Tachyzoites of Toxoplasma gondii are ingested by neutrophils and eosinophils through a process which can be significantly inhibited by previous incubation of the host cells with cytochalasin D. Although dividing zoites within the leukocytes could be observed, after 3 h of infection, killing of parasites within the parasitophorous vacuole was detected. Cytochemical studies showed that both in neutrophils and eosinophils there is a process of NADP(H) oxidase activation, which was higher in the latter.

Molecular mechanism and biological functions of c-Jun N-terminal kinase signalling via the c-Jun transcription factor.

The regulation of c-Jun transcriptional activity by Jun N-terminal kinase (JNK) has become a paradigm for understanding how mitogen-activated protein (MAP) kinase signalling pathways elicit specific changes in gene transcription through selective phosphorylation of nuclear transcription factors. Selective phosphorylation of c-Jun by JNK is determined by a specific docking motif in c-Jun, the delta region, which enables JNK to associate physically with c-Jun. Analogous MAP kinase docking motifs have subsequently been found in several other transcription factors, indicating that this is a general mechanism for ensuring specificity of signal transduction.