A randomized controlled trial of an online, compassion-based intervention for maternal psychological well-being in the first year postpartum

Objectives New self-help interventions have been called for to promote psychological well-being amongst mothers in the first year postpartum, with compassion-based interventions having potential in this regard. The present study developed and evaluated a low-intensity, online, compassion-based intervention for this population called Kindness for Mums Online (KFMO). Methods UK mothers of infants under one year (N = 206) participated in a pragmatic randomized controlled trial, comparing KFMO with a waitlist control. Results The effect of the intervention on well-being (the primary outcome) was small and was sensitive to the way missing data were treated. However, KFMO robustly increased self-compassion relative to control, from baseline (week 0) to post-intervention (week 6), and from baseline to follow-up (week 12). No effects were observed on other secondary outcomes. Conclusions The findings suggest that self-compassion can be increased in postpartum mothers via an accessible, low-intensity, web-based, self-help program. However, this did not translate into robust improvements in well-being. Study limitations include relatively high attrition rates and limited generalizability to more diverse samples

Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination

A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug

Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme β-glucuronidase. The sequences encoding C28 and human enzyme β-glucuronidase were joined by a sequence encoding a flexible linker, and were preceded by the IgGκ signal sequence for secretion of the fusion protein. A CHO cell line was engineered to secrete C28-β-glucuronidase fusion protein. Antibody specificity and enzyme activity were retained in the secreted fusion protein that had an apparent molecular mass of 100 kDa under denaturing conditions. The fusion protein was able to convert a non-toxic prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate to doxorubicin, resulting in cytotoxicity. A bystander effect was demonstrated, as doxorubicin was detected in all cells after N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate administration when only 10% of the cells expressed the fusion protein. This is the first fully human and functional fusion protein consisting of an scFv against epithelial cell adhesion molecule and human enzyme β-glucuronidase for future use in tumour-specific activation of a non-toxic glucuronide prodrug

Feasibility of using quadriceps-strengthening exercise to improve pain and sleep in a severely demented elder with osteoarthritis – a case report

BACKGROUND: Osteoarthritis (OA) of the knee, which is prevalent among older adults in nursing homes, causes significant pain and suffering, including disturbance of nocturnal sleep. One nonpharmacologic treatment option is quadriceps-strengthening exercise, however, the feasibility of such a treatment for reducing pain from OA in severely demented elders has not been studied. This report describes our test of the feasibility of such an exercise program, together with its effects on pain and sleep, in a severely demented nursing home resident. CASE PRESENTATION: The subject was an elderly man with severe cognitive impairment (Mini-Mental Status Exam score 4) and knee OA (Kellgren-Lawrence radiographic grade 4). He was enrolled in a 5-week, 10-session standardized progressive-resistance training program to strengthen the quadriceps, and completed all sessions. Pain was assessed with the Western Ontario and MacMaster OA Index (WOMAC) pain subscale, and sleep was assessed by actigraphy. The patient was able to perform the exercises, with a revision to the protocol. However, the WOMAC OA pain subscale proved inadequate for measuring pain in a patient with low cognitive functioning, and therefore the effects on pain were inconclusive. Although his sleep improved after the intervention, the influence of his medications and the amount of daytime sleep on his nighttime sleep need to be considered. CONCLUSIONS: A quadriceps-strengthening exercise program for treating OA of the knee is feasible in severely demented elders, although a better outcome measure is needed for pain

Ecological Guild Evolution and the Discovery of the World's Smallest Vertebrate

Living vertebrates vary drastically in body size, yet few taxa reach the extremely minute size of some frogs and teleost fish. Here we describe two new species of diminutive terrestrial frogs from the megadiverse hotspot island of New Guinea, one of which represents the smallest known vertebrate species, attaining an average body size of only 7.7 mm. Both new species are members of the recently described genus Paedophryne, the four species of which are all among the ten smallest known frog species, making Paedophryne the most diminutive genus of anurans. This discovery highlights intriguing ecological similarities among the numerous independent origins of diminutive anurans, suggesting that minute frogs are not mere oddities, but represent a previously unrecognized ecological guild

Mechanistic Basis of Branch-Site Selection in Filamentous Bacteria

Many filamentous organisms, such as fungi, grow by tip-extension and by forming new branches behind the tips. A similar growth mode occurs in filamentous bacteria, including the genus Streptomyces, although here our mechanistic understanding has been very limited. The Streptomyces protein DivIVA is a critical determinant of hyphal growth and localizes in foci at hyphal tips and sites of future branch development. However, how such foci form was previously unknown. Here, we show experimentally that DivIVA focus-formation involves a novel mechanism in which new DivIVA foci break off from existing tip-foci, bypassing the need for initial nucleation or de novo branch-site selection. We develop a mathematical model for DivIVA-dependent growth and branching, involving DivIVA focus-formation by tip-focus splitting, focus growth, and the initiation of new branches at a critical focus size. We quantitatively fit our model to the experimentally-measured tip-to-branch and branch-to-branch length distributions. The model predicts a particular bimodal tip-to-branch distribution results from tip-focus splitting, a prediction we confirm experimentally. Our work provides mechanistic understanding of a novel mode of hyphal growth regulation that may be widely employed

Germline sequencing in men with metastatic castration-resistant prostate cancer from the BARCODE2 study reveals a wide range of pathogenic variants in DNA repair genes

Abstract Background The presence of germline mutations plays an increasingly important role in risk assessment and treatment of prostate cancer (PrCa). Screening for high-risk mutations in subsets of patients is becoming routine. We explore the prevalence of germline genetic mutations in men with metastatic castration-resistant prostate cancer (mCRPC) recruited to the BARCODE2 trial. Methods The BARCODE2 trial is a two-part study investigating the response to carboplatin chemotherapy in mCRPC patients carrying a germline variant in a DNA repair gene (DRG). We report interim data from Part 1, in which participants are recruited for germline genetic testing using a customised next-generation sequencing panel consisting of 115 genes. Results These interim results (N = 220) demonstrate a similar frequency of germline DRG variants in mCRPC patients compared with previously published data (15% detection rate). No significant clinical differences were identified between all carriers and non-carriers, though BRCA2/ATM carriers were found to have a shorter time to mCRPC diagnosis. Conclusions Germline pathogenic/likely pathogenic (P/LP) variants in BRCA2 and ATM genes are associated with a shorter time to progression and rarer P/LP variants in other DRG genes may play a role in mCRPC. This justifies the use of routine screening of men with advanced PrCa for germline variants and supports the need for an expanded panel test. </jats:sec

Farmer-Scientist Knowledge Exchange

The last 25 years has seen a paradigm shift in the understanding of the nature of knowledge and how it is exchanged in the agricultural context. A changing backdrop, with the move towards multi-functional land management, persistent environmental problems and the search for sustainable agricultural approaches, has brought new challenges. At the same time the research agenda on knowledge has changed as an era of positivism, during which science and scientific experts were given unrivalled authority, was challenged by social studies of science that began to question the superiority of scientific knowledge, and value alternative forms of knowledge such as those held by farmers. Theory and practice of knowledge exchange in agriculture has evolved in line with this, shifting from a linear model of knowledge transfer to a perspective that integrates knowledge from multiple actors through facilitation and participation and emphasises learning in a social context

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org