Interleukin (IL)–12 and IL-23 Are Key Cytokines for Immunity against Salmonella in Humans

Patients with inherited deficiency of the interleukin (IL)–12/IL-23–interferon (IFN)–g axis show increased susceptibility to invasive disease caused by the intramacrophage pathogens salmonellae and mycobacteria. We analyzed data on 154 patients with such deficiency. Significantly more patients with IL-12/IL-23–component deficiency had a history of salmonella disease than did those with IFN-g–component deficiency. Salmonella disease was typically severe, extraintestinal, and caused by nontyphoidal serovars. These findings strongly suggest that IL-12/IL-23 is a key cytokine for immunity against salmonella in humans and that IL-12/IL-23 mediates this protective effect partly through IFN-g–independent pathways. Investigation of the IL-12/IL-23–IFN-g axis should be considered in patients with invasive salmonella disease

Latitude dependence of co-rotating shock acceleration

Energetic particle observations in the outer heliosphere (approx 12 A. U.) by the LECP instruments on the Voyager 1 and Voyager 2 spacecraft are discussed that show a definite latitude dependence of the number and intensity of particle enhancements produced by corotating interplanetary regions during an interval when no solar energetic particle events were observed. The particle enhancements are fewer in number and less intense at higher (approx 20 deg.) heliolatitudes. However, the similar spectral shapes of the accelerated particles at the two spacecraft indicate that the acceleration process is the same at the two latitudes, but less intense at the higher latitude

Charged Higgs phenomenology in the flipped two Higgs doublet model

We study the phenomenology of the charged Higgs boson in the "flipped" two Higgs doublet model, in which one doublet gives mass to up-type quarks and charged leptons and the other gives mass to down-type quarks. We present the charged Higgs branching ratios and summarize the indirect constraints. We extrapolate existing LEP searches for H+H- and Tevatron searches for t tbar with t --> H+ b into the flipped model and extract constraints on MH+ and the parameter tan(beta). We finish by reviewing existing LHC charged Higgs searches and suggest that the LHC reach in this model could be extended for charged Higgs masses below the tb threshold by considering t tbar with t --> H+ b and H+ --> q qbar, as has been used in Tevatron searches.Comment: 23 pages, 7 figures. V2: added refs on H+W- associated productio

Using shared goal setting to improve access and equity: a mixed methods study of the Good Goals intervention

Background: Access and equity in children’s therapy services may be improved by directing clinicians’ use of resources toward specific goals that are important to patients. A practice-change intervention (titled ‘Good Goals’) was designed to achieve this. This study investigated uptake, adoption, and possible effects of that intervention in children’s occupational therapy services. Methods: Mixed methods case studies (n = 3 services, including 46 therapists and 558 children) were conducted. The intervention was delivered over 25 weeks through face-to-face training, team workbooks, and ‘tools for change’. Data were collected before, during, and after the intervention on a range of factors using interviews, a focus group, case note analysis, routine data, document analysis, and researchers’ observations. Results: Factors related to uptake and adoptions were: mode of intervention delivery, competing demands on therapists’ time, and leadership by service manager. Service managers and therapists reported that the intervention: helped therapists establish a shared rationale for clinical decisions; increased clarity in service provision; and improved interactions with families and schools. During the study period, therapists’ behaviours changed: identifying goals, odds ratio 2.4 (95% CI 1.5 to 3.8); agreeing goals, 3.5 (2.4 to 5.1); evaluating progress, 2.0 (1.1 to 3.5). Children’s LoT decreased by two months [95% CI −8 to +4 months] across the services. Cost per therapist trained ranged from £1,003 to £1,277, depending upon service size and therapists’ salary bands. Conclusions: Good Goals is a promising quality improvement intervention that can be delivered and adopted in practice and may have benefits. Further research is required to evaluate its: (i) impact on patient outcomes, effectiveness, cost-effectiveness, and (ii) transferability to other clinical contexts

X-discontinuity and transition zone structure beneath Hawaii suggests a heterogeneous plume

The Hawaiian Island chain in the middle of the Pacific Ocean is a well-studied example of hotspot volcanism caused by an underlying upwelling mantle plume. The thermal and compositional nature of the plume alters the mantle phase transitions, which can be seen in the depth and amplitude of seismic discontinuities. This study utilises $>$ 5000 high quality receiver functions from Hawaiian island stations to detect P-to-s converted phases to image seismic discontinuities between 200 to 800 km depth. Common-conversion point stacks of the data are used to map out lateral variations in converted phase observations, while slowness stacks allow differentiation between true conversions from discontinuities and multiples. We find that the 410 discontinuity is depressed by 20 km throughout our study region, while the main 660 is around average depth throughout most of the area. To the southwest of the Big Island we observe splitting of the 660, with a major peak at 630 km, and a minor peak appearing at 675 km depth. This is inferred to represent the position of the hot plume at depth, with the upper discontinuity caused by an olivine phase transition and the lower by a garnet phase transition. In the upper mantle, a discontinuity is found across the region at depths varying between 290 to 350 km. Identifying multiples from this depth confirms the presence of a so-called X-discontinuity. To the east of the Big Island the X-discontinuity lies around 336 km and the associated multiple is particularly coherent and strong in amplitude. Strikingly, the discontinuity around 410 km disappears in this area. Synthetic modelling reveals that such observations can be explained by a silica phase transition from coesite to stishovite, consistent with widespread ponding of silica-saturated material at these depths around the plume. This material could represent eclogite enriched material, which is relatively silica-rich compared to pyrolite, spreading out from the plume to the east as a deep eclogite pool, a hypothesis which is consistent with dynamical models of thermochemical plumes. Therefore these results support the presence of a significant garnet and eclogite component within the Hawaiian mantle plume

Calcium supplements and cancer risk : a meta-analysis of randomised controlled trials

Peer reviewedPublisher PD

X-discontinuity and transition zone structure beneath Hawaii suggests a heterogeneous plume

The Hawaiian Island chain in the middle of the Pacific Ocean is a well-studied example of hotspot volcanism caused by an underlying upwelling mantle plume. The thermal and compositional nature of the plume alters the mantle phase transitions, which can be seen in the depth and amplitude of seismic discontinuities. This study utilises >5000 high quality receiver functions from Hawaiian island stations to detect P-to-s converted phases to image seismic discontinuities between 200 to 800 km depth. Common-conversion point stacks of the data are used to map out lateral variations in converted phase observations, while slowness stacks allow differentiation between true conversions from discontinuities and multiples. We find that the 410 discontinuity is depressed by 20 km throughout our study region, while the main 660 is around average depth throughout most of the area. To the southwest of the Big Island we observe splitting of the 660, with a major peak at 630 km, and a minor peak appearing at 675 km depth. This is inferred to represent the position of the hot plume at depth, with the upper discontinuity caused by an olivine phase transition and the lower by a garnet phase transition. In the upper mantle, a discontinuity is found across the region at depths varying between 290 to 350 km. Identifying multiples from this depth confirms the presence of a so-called X-discontinuity. To the east of the Big Island the X-discontinuity lies around 336 km and the associated multiple is particularly coherent and strong in amplitude. Strikingly, the discontinuity around 410 km disappears in this area. Synthetic modelling reveals that such observations can be explained by a silica phase transition from coesite to stishovite, consistent with widespread ponding of silica-saturated material at these depths around the plume. This material could represent eclogite enriched material, which is relatively silica-rich compared to pyrolite, spreading out from the plume to the east as a deep eclogite pool, a hypothesis which is consistent with dynamical models of thermochemical plumes. Therefore these results support the presence of a significant garnet and eclogite component within the Hawaiian mantle plume

Deletion of NH2− and COOH-terminal sequences destroys function of the Ca2+ ATPase of rabbit fast-twitch skeletal muscle sarcoplasmic reticulum

AbstractDeletion mutants of the Ca2+ ATPase of rabbit fast-twitch skeletal muscle sarcoplasmic reticulum (SERCA1a) were constructed and expressed in COS-1 cells. The mutants were expressed at levels 7- to 15-fold lower than the wild-type and were inactive. In vitro transcription-translation-insertion experiments showed that deletion of transmembrane sequences M1 and M2, but not of M8, M9, M10 or the NH2−terminal 30 amino acids inhibited the stable insertion of the enzyme into the membrane. Thus there was no correlation between loss of function and membrane insertion. A signal sequence for membrane insertion may exist in M1 and M2

Mesh inlay, mesh kit or native tissue repair for women having repeat anterior or posterior prolapse surgery: randomised controlled trial (PROSPECT)

Funding The project was funded by the National Institute for Health Research Health Technology Assessment Programme (Project Number 07/60/18). The Health Services Research Unit and the Health Economics Research Unit are funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. Acknowledgements The authors wish to thank the women who participated in the PROSPECT study. We also thank Margaret MacNeil for her secretarial support and data management; Dawn McRae and Lynda Constable for their trial management support; the programming team in CHaRT, led by Gladys McPherson; members of the Project Management Group for their ongoing advice and support of the study; and the staff at the recruitment sites who facilitated the recruitment, treatment and follow up of study participants.Peer reviewedPublisher PD