Pulsed electromagnetic energy treatment offers no clinical benefit in reducing the pain of knee osteoarthritis: a systematic review

Background The rehabilitation of knee osteoarthritis often includes electrotherapeutic modalities as well as advice and exercise. One commonly used modality is pulsed electromagnetic field therapy (PEMF). PEMF uses electro magnetically generated fields to promote tissue repair and healing rates. Its equivocal benefit over placebo treatment has been previously suggested however recently a number of randomised controlled trials have been published that have allowed a systematic review to be conducted. Methods A systematic review of the literature from 1966 to 2005 was undertaken. Relevant computerised bibliographic databases were searched and papers reviewed independently by two reviewers for quality using validated criteria for assessment. The key outcomes of pain and functional disability were analysed with weighted and standardised mean differences being calculated. Results Five randomised controlled trials comparing PEMF with placebo were identified. The weighted mean differences of the five papers for improvement in pain and function, were small and their 95% confidence intervals included the null. Conclusion This systematic review provides further evidence that PEMF has little value in the management of knee osteoarthritis. There appears to be clear evidence for the recommendation that PEMF does not significantly reduce the pain of knee osteoarthritis

The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Impaired myocardial function does not explain reduced left ventricular filling and stroke volume at rest or during exercise at high altitude

Impaired myocardial systolic contraction and diastolic relaxation have been suggested as possible mechanisms contributing to the decreased stroke volume (SV) observed at high altitude (HA). To determine whether intrinsic myocardial performance is a limiting factor in the generation of SV at HA, we assessed left ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy participants (aged 32 ± 7; mean ± SD) at rest and during exercise at sea level (SL; 344 m) and after 10 days at 5,050 m. In contrast to SL, LV end-diastolic volume was ∼19% lower at rest (P = 0.004) and did not increase during exercise despite a greater untwisting velocity. Furthermore, resting SV was lower at HA (∼17%; 60 ± 10 vs. 70 ± 8 ml) despite higher LV twist (43%), apical rotation (115%), and circumferential strain (17%). With exercise at HA, the increase in SV was limited (12 vs. 22 ml at SL), and LV apical rotation failed to augment. For the first time, we have demonstrated that EDV does not increase upon exercise at high altitude despite enhanced in vivo diastolic relaxation. The increase in LV mechanics at rest may represent a mechanism by which SV is defended in the presence of a reduced EDV. However, likely because of the higher LV mechanics at rest, no further increase was observed up to 50% peak power. Consequently, although hypoxia does not suppress systolic function per se, the capacity to increase SV through greater deformation during submaximal exercise at HA is restricted. during initial exposure to hypobaric hypoxia at high altitude (HA), cardiac output for a given absolute workload is increased to compensate for a lower arterial oxygen content before returning to baseline levels with acclimatization (8). However, after 2-5 days of acclimatization, the required cardiac output is generated through a lower stroke volume (SV) and higher heart rate (38). The reduced SV is suggestive of either lower ventricular filling, potentially caused in part by an impaired myocardial relaxation, or impaired ejection secondary to systolic contractile dysfunction. There is, however, a paucity of data in humans supporting a direct effect of hypoxia on myocardial function at HA (25, 41). The suggestion that hypoxia may impair myocardial systolic function during exercise was proposed nearly 50 years ago (3) and has been revisited more recently (27–29). Negative inotropic effects of hypoxia (arterial oxygen tension of 44 mmHg) have been shown in intact animal models (39) and isolated myocardial fibers under severe hypoxia (1% O2) (33). Exercise training under hypobaric hypoxia is also associated with altered mechanical properties at a cellular level in rodents (9), although chronic hypoxia alone did not decrease myofilament sensitivity to calcium. However, in contrast to animal studies, data in humans indicate that systolic function is maintained or enhanced at HA. For example, Suarez et al. (37) reported the maintenance of systolic function after gradual decompression to a barometric pressure of 282 mmHg, a finding that was subsequently confirmed by numerous investigations during acute and prolonged hypoxic exposure (6, 10, 12, 23, 31). However, of these studies, only Suarez et al. (37) investigated systolic function during light exercise (60 W), where function appeared to be maintained. It is not known whether systolic function is maintained at higher exercise intensities. It has also been speculated that reduced oxygen availability may impair diastolic relaxation at HA (15, 18) and thus explain the decreased left ventricular (LV) end-diastolic volume (EDV) commonly observed (2, 6, 18). However, despite numerous studies reporting a decrease in plasma volume and altered transmitral filling patterns (2, 6, 20), myocardial relaxation was only previously investigated during hypoxia in dogs (15), and no data exist examining LV relaxation during exercise at high altitude. By using sensitive, noninvasive imaging techniques (two-dimensional speckle tracking), it is now possible to examine the LV deformation mechanics (strain, twist, and untwist velocity) that underpin LV systolic and diastolic function. LV strain and twist have been shown to be sensitive measures of global and regional myocardial function, and reveal subclinical dysfunction in patients where ejection fraction is unchanged (16, 22). In addition, diastolic LV untwist velocity correlates well with invasive measures of LV stiffness and provides a temporal link between relaxation and the development of intraventricular pressure gradients (30, 43). Therefore, examination of LV mechanics at HA may determine whether the decreased SV observed at HA is dependent on impaired myocardial relaxation and/or myocardial contractile dysfunction or confirm previous findings of preserved ventricular function during exercise (37). We therefore assessed systolic and diastolic ventricular mechanics during incremental exercise at sea level and HA to examine whether impaired myocardial relaxation or systolic dysfunction explains the previously reported reduction in SV at HA. We hypothesized that at HA, 1) ventricular filling would be lower at rest and during exercise and would be accompanied by a reduction in untwist velocity and 2) systolic mechanics would be impaired during exercise at HA

Advancing Tests of Relativistic Gravity via Laser Ranging to Phobos

Phobos Laser Ranging (PLR) is a concept for a space mission designed to advance tests of relativistic gravity in the solar system. PLR's primary objective is to measure the curvature of space around the Sun, represented by the Eddington parameter $\gamma$, with an accuracy of two parts in $10^7$, thereby improving today's best result by two orders of magnitude. Other mission goals include measurements of the time-rate-of-change of the gravitational constant, $G$ and of the gravitational inverse square law at 1.5 AU distances--with up to two orders-of-magnitude improvement for each. The science parameters will be estimated using laser ranging measurements of the distance between an Earth station and an active laser transponder on Phobos capable of reaching mm-level range resolution. A transponder on Phobos sending 0.25 mJ, 10 ps pulses at 1 kHz, and receiving asynchronous 1 kHz pulses from earth via a 12 cm aperture will permit links that even at maximum range will exceed a photon per second. A total measurement precision of 50 ps demands a few hundred photons to average to 1 mm (3.3 ps) range precision. Existing satellite laser ranging (SLR) facilities--with appropriate augmentation--may be able to participate in PLR. Since Phobos' orbital period is about 8 hours, each observatory is guaranteed visibility of the Phobos instrument every Earth day. Given the current technology readiness level, PLR could be started in 2011 for launch in 2016 for 3 years of science operations. We discuss the PLR's science objectives, instrument, and mission design. We also present the details of science simulations performed to support the mission's primary objectives.Comment: 25 pages, 10 figures, 9 table

Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial

Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo

A preliminary fish survey of the estuaries on the southeast coast of South Africa, Kayser’s Beach – Kei Mouth: a comparative study

A basic ichthyofaunal and physico-chemical survey of estuaries on the southeast coast of South Africa from Kayser’s Beach to Kei Mouth was undertaken during September and October 1996. Twenty-eight (28) estuaries have been identified along this stretch of coastline, and these were grouped into three types: small (<10 ha) predominantly closed estuaries, moderate to large (> 10 ha) predominantly closed estuaries, and predominantly open estuaries. Multivariate analyses revealed significant differences between estuarine types both in terms of their physico-chemical characteristics and fish communities. These features were consistent with those reported in other parts of the south and southeast coast. Overall, predominantly closed estuaries had a lower species diversity than predominantly open estuaries and smaller systems had a lower species diversity than moderate to large systems. Although differences were observed between estuarine types, most systems provided important habitat for a number of estuarine-dependent marine species as well as resident species, which were often recorded in high numbers. Many of these species were also endemic, which further emphasises the importance of these estuaries in maintaining ichthyofaunal diversity in the region. This survey represents one of the few fish surveys undertaken along this little-studied section of coastline.Keywords: ichthyofauna, estuarine survey, fish habitat, southeast coas

Prevalence and dynamics of ribosomal DNA micro-heterogeneity are linked to population history in two contrasting yeast species

Despite the considerable number and taxonomic breadth of past and current genome sequencing projects, many of which necessarily encompass the ribosomal DNA, detailed information on the prevalence and evolutionary significance of sequence variation in this ubiquitous genomic region are severely lacking. Here, we attempt to address this issue in two closely related yet contrasting yeast species, the baker's yeast Saccharomyces cerevisiae and the wild yeast Saccharomyces paradoxus. By drawing on existing datasets from the Saccharomyces Genome Resequencing Project, we identify a rich seam of ribosomal DNA sequence variation, characterising 1,068 and 970 polymorphisms in 34 S. cerevisiae and 26 S. paradoxus strains respectively. We discover the two species sets exhibit distinct mutational profiles. Furthermore, we show for the first time that unresolved rDNA sequence variation resulting from imperfect concerted evolution of the ribosomal DNA region follows a U-shaped allele frequency distribution in each species, similar to loci that evolve under non-concerted mechanisms but arising through rather different evolutionary processes. Finally, we link differences between the shapes of these allele frequency distributions to the two species' contrasting population histories

Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing

The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys. These data demonstrate the potential for the anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD-1/PD-L1 signaling, in the treatment of MM and other B cell malignancies.This work was supported by a Sir Henry Dale Fellowship (J.R.J.) jointly funded by the Wellcome Trust and the Royal Society (grant number: 099966/Z/12/Z). PhD studentships (S.A.M. and M.J.H.) were funded by the Wellcome Trust (grant number: 102195/Z/13/Z)

Autism, Identity and Clinical Practice: Supporting Positive Identity Development in Neurodivergent Children and Young People

Purpose: Developing a positive neurodivergent identity is increasingly recognised as crucial for individuals’ well-being. As part of service improvement, we completed a qualitative investigation of the experiences of clinicians in a Child and Adolescent Mental Health Service Neurodevelopmental Conditions team providing support for autistic children's developing positive neurodivergent identity. Methods: Nine semi-structured interviews with clinicians were held to explore their experiences of supporting children and young people's positive identity development. Interpretative Phenomenological Analysis was used to explore and understand clinicians’ experiences. Results: Four superordinate themes were identified: (1) A flexible neuroaffirmative concept of positive autistic identity; (2) Being honest and balanced: acknowledging challenges for young autistic people; (3) Developing an identity through relationships with others; and (4) Professional vulnerability in navigating neurodivergent identities: The importance of self-reflexivity. Conclusion: In line with our theoretical understanding of identity development, the child's network and environment was seen as crucial for their developing identity. In line with research into assimilating an identity as part of a neurominority, a flexible but neuroaffirmative approach was seen as vital. Novel clinical experiences included the need for staff support and reflective spaces to consider their own relationship to neurodiversity. Lay Abstract: Research shows that viewing yourself positively (your identity) helps neurodivergent people to have better well-being overall. We wanted to understand what the professionals working with children and teenagers in an NHS child and adolescent mental health service think about supporting young autistic people to think positively about their identity as neurodivergent people, so that we could learn about what is helpful and what is challenging. We interviewed nine people from different professions (such as doctors, psychologists and social workers) who worked in a team for autistic children and teenagers, asking the professionals about their experience of supporting the children and teenagers to develop positive beliefs about being autistic. We analysed the interviews using a method that helps us understand different people's experiences. We found four main themes in the interviews: (1) Understanding and explaining autism and neurodivergence in flexible, positive ways; (2) Understanding how challenging it can be to grow up as an autistic young person; (3) Understanding the different people in a child's life who influence how they see themselves; and (4) Professionals needing to have time and support to think about their own relationship to neurodiversity. Our findings fit with theories that explain how identity develops in childhood, with people around each child being important influences on how they see themselves. The findings fit with a need to hold positive views about autism and neurodivergence in society and in healthcare. We also found that staff may need more support and professional spaces to think about their own identity and relationship to neurodiversity