What have we learnt from palaeoclimate simulations?

There has been a gradual evolution in the way that palaeoclimate modelling and palaeoenvironmental data are used together to understand how the Earth System works, from an initial and largely descriptive phase through explicit hypothesis testing to diagnosis of underlying mechanisms. Analyses of past climate states are now regarded as integral to the evaluation of climate models, and have become part of the toolkit used to assess the likely realism of future projections. Palaeoclimate assessment has demonstrated that changes in large-scale features of climate that are governed by the energy and water balance show consistent responses to changes in forcing in different climate states, and these consistent responses are reproduced by climate models. However, state-of-the-art models are still largely unable to reproduce observed changes in climate at a regional scale reliably. While palaeoclimate analyses of state-of-the-art climate models suggest an urgent need for model improvement, much work is also needed on extending and improving palaeoclimate reconstructions and quantifying and reducing both numerical and interpretative uncertainties

Priority setting in health care: Lessons from the experiences of eight countries

All health care systems face problems of justice and efficiency related to setting priorities for allocating a limited pool of resources to a population. Because many of the central issues are the same in all systems, the United States and other countries can learn from the successes and failures of countries that have explicitly addressed the question of health care priorities

Omentalisation as adjunctive treatment of an infected femoral nonunion fracture: a case report

A three-year-old male working border collie with an infected femoral nonunion fracture was managed in a two-stage procedure involving debridement and omentalisation, followed by stabilisation with a bone plate and an autogenous cancellous bone graft. Osseous union was documented radiographically 16 weeks after surgery. Telephone follow-up one year later revealed the dog had returned to full working function without evidence of lameness. To the authors' knowledge, this is the first clinical case described in the veterinary literature using omentalisation as an adjunct to the management of an infected, biologically inactive nonunion fracture

Including the public in pandemic planning: a deliberative approach

Background: Against a background of pandemic threat posed by SARS and avian H5N1 influenza, this study used deliberative forums to elucidate informed community perspectives on aspects of pandemic planning. Methods: Two deliberative forums were carried out with members of the South Australian community. The forums were supported by a qualitative study with adults and youths, systematic reviews of the literature and the involvement of an extended group of academic experts and policy makers. The forum discussions were recorded with simultaneous transcription and analysed thematically. Results: Participants allocated scarce resources of antiviral drugs and pandemic vaccine based on a desire to preserve society function in a time of crisis. Participants were divided on the acceptability of social distancing and quarantine measures. However, should such measures be adopted, they thought that reasonable financial, household and psychological support was essential. In addition, provided such support was present, the participants, in general, were willing to impose strict sanctions on those who violated quarantine and social distancing measures. Conclusions: The recommendations from the forums suggest that the implementation of pandemic plans in a severe pandemic will be challenging, but not impossible. Implementation may be more successful if the public is engaged in pandemic planning before a pandemic, effective communication of key points is practiced before and during a pandemic and if judicious use is made of supportive measures to assist those in quarantine or affected by social isolation measures.Annette J Braunack-Mayer, Jackie M Street, Wendy A Rogers, Rodney Givney, John R Moss, Janet E Hiller, Flu Views tea

Human Mesenchymal Stem Cells Protect Human Islets from Pro-Inflammatory Cytokines

Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0×106 human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0×106 bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation

Patients' and urologists' preferences for prostate cancer treatment: A discrete choice experiment

__Abstract__ Background: Patients' preferences are important for shared decision making. Therefore, we investigated patients' and urologists' preferences for treatment alternatives for early prostate cancer (PC). Methods: A discrete choice experiment was conducted among 150 patients who were waiting for their biopsy results, and 150 urologists. Regression analysis was used to determine patients' and urologists' stated preferences using scenarios based on PC treatment modality (radiotherapy, surgery, and active surveillance (AS)), and risks of urinary incontinence and erectile dysfunction.Results:The response rate was 110 out of 150 (73%) for patients and 50 out of 150 (33%) for urologists. Risk of urinary incontinence was an important determinant of both patients' and urologists' stated preferences for PC treatment (P<0.05). Treatment modality also influenced patients' stated preferences (P<0.05), whereas the risk of erectile dysfunction due to radiotherapy was mainly important to urologists (P<0.05). Both patients and urologists preferred AS to radical treatment, with the exception of patients with anxious/depressed feelings who preferred radical treatment to AS. Conclusion: Although patients and urologists generally may prefer similar treatments for PC, they showed different trade-offs between various specific treatment aspects. This implies that urologists need to be aware of potential differences compared with the patient's perspective on treatment decisions in shared decision making on PC treatment

Mowat-Wilson syndrome: growth charts

Background Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of theZEB2gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children. Results In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build. Conclusions These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS

Patient-provider interaction from the perspectives of type 2 diabetes patients in Muscat, Oman: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Patients' expectations and perceptions of the medical encounter and interactions are important tools in diabetes management. Some problems regarding the interaction during encounters may be related to a lack of communication skills on the part of either the physician or the patient.</p> <p>This study aimed at exploring the perceptions of type 2 diabetes patients regarding the medical encounters and quality of interactions with their primary health-care providers.</p> <p>Methods</p> <p>Four focus group discussions (two women and two men groups) were conducted among 27 purposively selected patients (13 men and 14 women) from six primary health-care centres in Muscat, Oman. Qualitative content analysis was applied.</p> <p>Results</p> <p>The patients identified some weaknesses regarding the patient-provider communication like: unfriendly welcoming; interrupted consultation privacy; poor attention and eye contact; lack of encouraging the patients to ask questions on the providers' side; and inability to participate in medical dialogue or express concerns on the patients' side. Other barriers and difficulties related to issues of patient-centeredness, organization of diabetes clinics, health education and professional competency regarding diabetes care were also identified.</p> <p>Conclusion</p> <p>The diabetes patients' experiences with the primary health-care providers showed dissatisfaction with the services. We suggest appropriate training for health-care providers with regard to diabetes care and developing of communication skills with emphasis on a patient-centred approach. An efficient use of available resources in diabetes clinics and distributing responsibilities between team members in close collaboration with patients and their families seems necessary. Further exploration of the providers' work situation and barriers to good interaction is needed. Our findings can help the policy makers in Oman, and countries with similar health systems, to improve the quality and organizational efficiency of diabetes care services.</p

The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss

Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone

Acoustic Overexposure Increases the Expression of VGLUT-2 Mediated Projections from the Lateral Vestibular Nucleus to the Dorsal Cochlear Nucleus

The dorsal cochlear nucleus (DCN) is a first relay of the central auditory system as well as a site for integration of multimodal information. Vesicular glutamate transporters VGLUT-1 and VGLUT-2 selectively package glutamate into synaptic vesicles and are found to have different patterns of organization in the DCN. Whereas auditory nerve fibers predominantly co-label with VGLUT-1, somatosensory inputs predominantly co-label with VGLUT-2. Here, we used retrograde and anterograde transport of fluorescent conjugated dextran amine (DA) to demonstrate that the lateral vestibular nucleus (LVN) exhibits ipsilateral projections to both fusiform and deep layers of the rat DCN. Stimulating the LVN induced glutamatergic synaptic currents in fusiform cells and granule cell interneurones. We combined the dextran amine neuronal tracing method with immunohistochemistry and showed that labeled projections from the LVN are co-labeled with VGLUT-2 by contrast to VGLUT-1. Wistar rats were exposed to a loud single tone (15 kHz, 110 dB SPL) for 6 hours. Five days after acoustic overexposure, the level of expression of VGLUT-1 in the DCN was decreased whereas the level of expression of VGLUT-2 in the DCN was increased including terminals originating from the LVN. VGLUT-2 mediated projections from the LVN to the DCN are likely to play a role in the head position in response to sound. Amplification of VGLUT-2 expression after acoustic overexposure could be a compensatory mechanism from vestibular inputs in response to hearing loss and to a decrease of VGLUT-1 expression from auditory nerve fibers