Subchondral bone in osteoarthritis: association between MRI texture analysis and histomorphometry.

OBJECTIVE: Magnetic resonance imaging (MRI) texture analysis is a method of analyzing subchondral bone alterations in osteoarthritis (OA). The objective of this study was to evaluate the association between MR texture analysis and ground-truth subchondral bone histomorphometry at the tibial plateau. DESIGN: The local research ethics committee approved the study. All subjects provided written, informed consent. This was a cross-sectional study carried out at our institution between February and August 2014. Ten participants aged 57-84 with knee OA scheduled for total knee arthroplasty (TKA) underwent pre-operative MRI of the symptomatic knee at 3T using a high spatial-resolution coronal T1 weighted sequence. Tibial plateau explants obtained at the time of TKA underwent histological preparation to allow calculation of bone volume fraction (BV.TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N). Texture analysis was performed on the tibial subchondral bone of MRI images matched to the histological sections. Regression models were created to assess the association of texture analysis features with BV.TV, Tb.Th, Tb.Sp and Tb.N. RESULTS: MRI texture features were significantly associated with BV.TV (R2 = 0.76), Tb.Th (R2 = 0.47), Tb.Sp (R2 = 0.75) and Tb.N (R2 = 0.60, all P < 0.001). Simple gray-value histogram based texture features demonstrated the highest standardized regression coefficients for each model. CONCLUSION: MRI texture analysis features were significantly associated with ground-truth subchondral bone histomorphometry at the tibial plateau.Royal College of Radiologists Pump Priming Gran

Systematic review and meta-analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis.

OBJECTIVE: To assess reliability and discriminative validity of cartilage compositional magnetic resonance imaging (MRI) in knee osteoarthritis (OA). DESIGN: The study was carried out per PRISMA recommendations. We searched MEDLINE and EMBASE (1974 - present) for eligible studies. We performed qualitative synthesis of reliability data. Where data from at least two discrimination studies were available, we estimated pooled standardized mean difference (SMD) between subjects with and without OA. Discrimination analyses compared controls and subjects with mild OA (Kellgren-Lawrence (KL) grade 1-2), severe OA (KL grade 3-4) and OA not otherwise specified (NOS) where not possible to stratify. We assessed quality of the evidence using Quality Appraisal of Diagnostic Reliability (QAREL) and Quality Assessment of Diagnostic Accuracy (QUADAS-2) tools. RESULTS: Fifty-eight studies were included in the reliability analysis and 26 studies were included in the discrimination analysis, with data from a total of 2,007 knees. Intra-observer, inter-observer and test-retest reliability of compositional techniques were excellent with most intraclass correlation coefficients >0.8 and coefficients of variation <10%. T1rho and T2 relaxometry were significant discriminators between subjects with mild OA and controls, and between subjects with OA (NOS) and controls (P < 0.001). T1rho showed best discrimination for mild OA (SMD [95% CI] = 0.73 [0.40 to 1.06], P < 0.001) and OA (NOS) (0.60 [0.41 to 0.80], P < 0.001). Quality of evidence was moderate for both parts of the review. CONCLUSIONS: Cartilage compositional MRI techniques are reliable and, in the case of T1rho and T2 relaxometry, can discriminate between subjects with OA and controls

Strong decline in female sterilization rates in Norway after the introduction of a new copayment system: a registry based study

<p>Abstract</p> <p>Background</p> <p>January 1, 2002, copayment for outpatient female sterilization in Norwegian public hospitals increased from 33 euros to 750 euros after a revision of the health care system. The aim of the present study was to investigate the effect of the new copayment system on female sterilization epidemiology.</p> <p>Methods</p> <p>We retrieved data on all female sterilizations 1999–2005 (N = 23 1333) from the Norwegian Patient Register, an administrative register to which it is mandatory for all hospitals to report. Sterilizations with diagnostic codes indicative of vaginal delivery, caesarean section, spontaneous abortion, ectopic pregnancy, and termination of pregnancy were analyzed separately. All other sterilizations were defined as "interval sterilization".</p> <p>Results</p> <p>An abrupt fall in female sterilization was observed after the raise in copayment. Age-adjusted incidence rates dropped from 6.3–6.8 per 1000 women in 1999–2001 to 2.2–2.3 per 1000 women during 2002–2005. Interval sterilizations dropped to 25% of the previous level after the rise in copayment while sterilizations in conjunction with caesarean section and postpartum sterilization remained constant.</p> <p>Conclusion</p> <p>For many Norwegian women seeking contraception, sterilization is no longer an available alternative.</p

Mechanical Systems with Symmetry, Variational Principles, and Integration Algorithms

This paper studies variational principles for mechanical systems with symmetry and their applications to integration algorithms. We recall some general features of how to reduce variational principles in the presence of a symmetry group along with general features of integration algorithms for mechanical systems. Then we describe some integration algorithms based directly on variational principles using a discretization technique of Veselov. The general idea for these variational integrators is to directly discretize Hamilton’s principle rather than the equations of motion in a way that preserves the original systems invariants, notably the symplectic form and, via a discrete version of Noether’s theorem, the momentum map. The resulting mechanical integrators are second-order accurate, implicit, symplectic-momentum algorithms. We apply these integrators to the rigid body and the double spherical pendulum to show that the techniques are competitive with existing integrators

Measuring maternal mortality : an overview of opportunities and options for developing countries

Background:There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015. Methods: Since the launch of the Safe Motherhood Initiative in 1987, new opportunities for data capture have arisen and new methods have been developed, tested and used. This paper provides a pragmatic overview of these methods and the optimal measurement strategies for different developing country contexts. Results: There are significant recent advances in the measurement of maternal mortality, yet also room for further improvement, particularly in assessing the magnitude and direction of biases and their implications for different data uses. Some of the innovations in measurement provide efficient mechanisms for gathering the requisite primary data at a reasonably low cost. No method, however, has zero costs. Investment is needed in measurement strategies for maternal mortality suited to the needs and resources of a country, and which also strengthen the technical capacity to generate and use credible estimates. Conclusion: Ownership of information is necessary for it to be acted upon: what you count is what you do. Difficulties with measurement must not be allowed to discourage efforts to reduce maternal mortality. Countries must be encouraged and enabled to count maternal deaths and act.WJG is funded partially by the University of Aberdeen. OMRC is partially funded by the London School of Hygiene and Tropical Medicine. CS and SA are partially funded by Johns Hopkins University. CAZ is funded by the Health Metrics Network at the World Health Organization. WJG, OMRC, CS and SA are also partially supported through an international research program, Immpact, funded by the Bill & Melinda Gates Foundation, the Department for International Development, the European Commission and USAID

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

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

Mapping Groundwater Dependent Ecosystems in California

BACKGROUND: Most groundwater conservation and management efforts focus on protecting groundwater for drinking water and for other human uses with little understanding or focus on the ecosystems that depend on groundwater. However, groundwater plays an integral role in sustaining certain types of aquatic, terrestrial and coastal ecosystems, and their associated landscapes. Our aim was to illuminate the connection between groundwater and surface ecosystems by identifying and mapping the distribution of groundwater dependent ecosystems (GDEs) in California. METHODOLOGY/PRINCIPAL FINDINGS: To locate where groundwater flow sustains ecosystems we identified and mapped groundwater dependent ecosystems using a GIS. We developed an index of groundwater dependency by analyzing geospatial data for three ecosystem types that depend on groundwater: (1) springs and seeps; (2) wetlands and associated vegetation alliances; and (3) stream discharge from groundwater sources (baseflow index). Each variable was summarized at the scale of a small watershed (Hydrologic Unit Code-12; mean size = 9,570 ha; n = 4,621), and then stratified and summarized to 10 regions of relative homogeneity in terms of hydrologic, ecologic and climatic conditions. We found that groundwater dependent ecosystems are widely, although unevenly, distributed across California. Although different types of GDEs are clustered more densely in certain areas of the state, watersheds with multiple types of GDEs are found in both humid (e.g. coastal) and more arid regions. Springs are most densely concentrated in the North Coast and North Lahontan, whereas groundwater dependent wetlands and associated vegetation alliances are concentrated in the North and South Lahontan and Sacramento River hydrologic regions. The percentage of land area where stream discharge is most dependent on groundwater is found in the North Coast, Sacramento River and Tulare Lake regions. GDE clusters are located at the highest percentage in the North Coast (an area of the highest annual rainfall totals), North Lahontan (an arid, high desert climate with low annual rainfall), and Sacramento River hydrologic regions. That GDEs occur in such distinct climatic and hydrologic settings reveals the widespread distribution of these ecosystems. CONCLUSIONS/SIGNIFICANCE: Protection and management of groundwater-dependent ecosystems are hindered by lack of information on their diversity, abundance and location. By developing a methodology that uses existing datasets to locate GDEs, this assessment addresses that knowledge gap. We report here on the application of this method across California, but believe the method can be expanded to regions where spatial data exist

BAFF Mediates Splenic B Cell Response and Antibody Production in Experimental Chagas Disease

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Central and South America. It affects 20 million people and about 100 million people are at risk of infection in endemic areas. Some cases have been identified in non-endemic countries as a consequence of blood transfusion and organ transplantation. Chagas disease presents three stages of infection. The acute phase appears one to two weeks after infection and includes fever, swelling around the bite site, enlarged lymph glands and spleen, and fatigue. This stage is characterized by circulating parasites and many immunological disturbances including a massive B cell response. In general, the acute episode self-resolves in about 2 months and is followed by a clinically silent indeterminate phase characterized by absence of circulating parasites. In about one-third of the cases, the indeterminate phase evolves into a chronic phase with clinically defined cardiac or digestive disturbances. Current knowledge suggests that the persistence of parasites coupled with an unbalanced immune response sustain inflammatory response in the chronic stage. We believe that an effective treatment for chronic Chagas disease should combine antiparasitic drugs with immunomodulators aimed at reducing inflammation and autoreactive response. Our findings enlighten a new role of BAFF-BAFF-R signaling in parasite infection that partially controls polyclonal B cell response but not parasitespecific class-switched primary effectors B cells