What the geological past can tell us about the future of the ocean’s twilight zone

Paleontological reconstructions of plankton community structure during warm periods of the Cenozoic (last 66 million years) reveal that deep-dwelling ‘twilight zone’ (200–1000 m) plankton were less abundant and diverse, and lived much closer to the surface, than in colder, more recent climates. We suggest that this is a consequence of temperature’s role in controlling the rate that sinking organic matter is broken down and metabolized by bacteria, a process that occurs faster at warmer temperatures. In a warmer ocean, a smaller fraction of organic matter reaches the ocean interior, affecting food supply and dissolved oxygen availability at depth. Using an Earth system model that has been evaluated against paleo observations, we illustrate how anthropogenic warming may impact future carbon cycling and twilight zone ecology. Our findings suggest that significant changes are already underway, and without strong emissions mitigation, widespread ecological disruption in the twilight zone is likely by 2100, with effects spanning millennia thereafter

'What vision?': experiences of Team members in a community service for adults with intellectual disabilities.

BACKGROUND: In the UK, the closure of 'long-stay' hospitals was accompanied by the development of community teams (CTs) to support people with intellectual disabilities (IDs) to live in community settings. The self-reported experiences of staff working in such teams have been neglected. METHODS: Focusing on a single county-wide service, comprising five multi-disciplinary and inter-agency CTs, we measured perceptions among the health care and care management Team members of (1) their personal well-being; (2) the functioning of their team; and (3) the organisation's commitment to quality, and culture. RESULTS: Almost three-quarters of the questionnaires were returned (73/101; 72%). The scores of health care practitioners and care managers were very similar: (1) the MBI scores of more than half the respondents were 'of concern'; (2) similarly, almost four in ten respondents' scores on the Vision scale of the TCI were 'of concern'; (3) the perceived commitment to quality (QIIS-II Part 2) was uncertain; and (4) the organisational culture (QIIS-II, Part 1) was viewed as primarily hierarchical. DISCUSSION: The perceived absence of a vision for the service, combined with a dominant culture viewed by its members as strongly focussed on bureaucracy and process, potentially compromises the ability of these CTs to respond proactively to the needs of people with IDs. Given the changes in legislation, policy and practice that have taken place since CTs were established, it would be timely to revisit their role and purpose.We are grateful to all our participants in the IDP, without whom the study could not have taken place, to Professor Eivor Oborn (Warwick Business School) for her insights in the development of the study. Funding was provided by the NIHR’s Collaboration for Health Research & Care (CLAHRC) for Cambridgeshire & Peterborough. The preparation of the paper was funded by the NIHR’s CLAHRC East of England (ICHC, KAW, AJH, AL, EJ, APW). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.This is the author accepted manuscript. The final version is available from Wiley via https://doi.org/10.1111/jir.1231

A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis

Background \ud Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis. \ud \ud Methods \ud One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change – a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests. \ud \ud Results \ud Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS. \ud \ud Conclusion \ud Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores

Mitotic Errors Promote Genomic Instability and Leukemia in a Novel Mouse Model of Fanconi Anemia

© 2021 Edwards, Mitchell, Abdul-Sater, Chan, Sun, Sheth, He, Jiang, Yuan, Sharma, Czader, Chin, Liu, de Cárcer, Nalepa, Broxmeyer, Clapp and Sierra Potchanant.Fanconi anemia (FA) is a disease of genomic instability and cancer. In addition to DNA damage repair, FA pathway proteins are now known to be critical for maintaining faithful chromosome segregation during mitosis. While impaired DNA damage repair has been studied extensively in FA-associated carcinogenesis in vivo, the oncogenic contribution of mitotic abnormalities secondary to FA pathway deficiency remains incompletely understood. To examine the role of mitotic dysregulation in FA pathway deficient malignancies, we genetically exacerbated the baseline mitotic defect in Fancc-/- mice by introducing heterozygosity of the key spindle assembly checkpoint regulator Mad2. Fancc-/-;Mad2+/- mice were viable, but died from acute myeloid leukemia (AML), thus recapitulating the high risk of myeloid malignancies in FA patients better than Fancc-/-mice. We utilized hematopoietic stem cell transplantation to propagate Fancc-/-; Mad2+/- AML in irradiated healthy mice to model FANCC-deficient AMLs arising in the non-FA population. Compared to cells from Fancc-/- mice, those from Fancc-/-;Mad2+/- mice demonstrated an increase in mitotic errors but equivalent DNA cross-linker hypersensitivity, indicating that the cancer phenotype of Fancc-/-;Mad2+/- mice results from error-prone cell division and not exacerbation of the DNA damage repair defect. We found that FANCC enhances targeting of endogenous MAD2 to prometaphase kinetochores, suggesting a mechanism for how FANCC-dependent regulation of the spindle assembly checkpoint prevents chromosome mis-segregation. Whole-exome sequencing revealed similarities between human FA-associated myelodysplastic syndrome (MDS)/AML and the AML that developed in Fancc-/-; Mad2+/- mice. Together, these data illuminate the role of mitotic dysregulation in FA-pathway deficient malignancies in vivo, show how FANCC adjusts the spindle assembly checkpoint rheostat by regulating MAD2 kinetochore targeting in cell cycle-dependent manner, and establish two new mouse models for preclinical studies of AML.This work was supported by the NIH R01-HL132921-01A1 award (DWC), St. Baldrick’s Foundation Scholar award (GN), Heroes Foundation (GN), the Bone Marrow Failure Research Fund at Riley Children’s Foundation (GN), NIH T32 HL007910 “Basic Science Studies on Gene Therapy of Blood Diseases” grant (ES), NIH Diversity Supplement 3R01HL132921-03S1 (ES), and NCI 1F30CA200227-01A1 fellowship (DE)

Ancestral bias in the Hras1 gene and distal Chromosome 7 among inbred mice

Inbred strains of mice vary in their frequency of liver tumors initiated by a mutation in the Hras1 (H-ras) proto-oncogene. We sequenced 4.5 kb of the Hras1 gene on distal Chr 7 in a diverse set of 12 commonly used laboratory inbred strains of mice and detected no sequence variation to account for strain-specific differences in Hras1 mutation prevalence. Furthermore, the Hras1 sequence is essentially monoallelic for an ancestral gene derived from the M. m. domesticus species. To determine if the monoallelism and associated low rate of polymorphism are unique to Hras1 or representative of the general chromosomal locale, we extended the sequence analysis to 12 genes in the final 8 Mb of distal Chr 7. A region of at least 2.5 Mb that encompasses several genes, including Hras1 and the H19/Igf2 loci, demonstrates virtually no sequence variation. The 12 inbred strains share one dominant haplotype derived from the M. m. domesticus allele. Chromosomal regions flanking the monoallelic segment exhibit a significantly higher rate of variation and multiple haplotypes, a majority of which are attributed to M. m. domesticus or M. m. musculus ancestry

An Overview of the Management of Flexor Tendon Injuries

Flexor tendon injuries still remain a challenging condition to manage to ensure optimal outcome for the patient. Since the first flexor tendon repair was described by Kirchmayr in 1917, several approaches to flexor tendon injury have enabled successful repairs rates of 70-90%. Primary surgical repair results in better functional outcome compared to secondary repair or tendon graft surgery. Flexor tendon injury repair has been extensively researched and the literature demonstrates successful repair requires minimal gapping at the repair site or interference with tendon vascularity, secure suture knots, smooth junction of tendon end and having sufficient strength for healing. However, the exact surgical approach to achieve success being currently used among surgeons is still controversial. Therefore, this review aims to discuss the results of studies demonstrating the current knowledge regarding the optimal approach for flexor tendon repair. Post-operative rehabilitation for flexor tendon surgery is another area, which has caused extensive debate in hand surgery. The trend to more active mobilisation protocols seems to be favoured but further study in this area is needed to find the protocol, which achieves function and gliding but avoids rupture of the tendons. Lastly despite success following surgery complications commonly still occur post surgery, including adhesion formation, tendon rupture and stiffness of the joints. Therefore, this review aims to discuss the appropriate management of these difficulties post surgery. New techniques in management of flexor tendon will also be discussed including external laser devices, addition of growth factors and cytokines

Self-medication for infants with colic in Lagos, Nigeria

<p>Abstract</p> <p>Background</p> <p>Infantile colic is a self-limiting condition that is distributed worldwide. It is often misdiagnosed as an organic disease for which an infant is admitted to the hospital. Many studies have described the aetiopathogenesis, pharmacologic and non-pharmacologic management of colic but none has evaluated self-medication for infants with colic. The aim of this study was therefore to determine the knowledge of Nigerian mothers about colic, their home-based management, extent of self-medication for the infants with colic and the types of medicines involved.</p> <p>Methods</p> <p>It is a prospective study conducted at the vaccination clinics of 20 primary health care centres, each from different Local Government Areas in Lagos, Nigeria. Eight hundred mothers that brought their infants for vaccination between April and September, 2006 were interviewed with open-and close-ended questionnaire.</p> <p>Results</p> <p>Six hundred and eighty three (85.4%) mothers claimed they had a good knowledge of colic. Incessant and excessive cry was the main clinical feature of colic identified by 430(62.9%) mothers. Three hundred and seventy eight (67.7%) infants were treated by self-medication, 157 (28.1%) sought medical intervention and 17 (3.1%) were treated at a traditional birth attendant home. Herbal medicines constituted 51.8% of the self-medicated medicines, of which 48 (26.2%) were "Ororo Ogiri". Nospamin^®(49.5%) and Gripe water^®(43.0%) were the two frequently prescribed and self-medicated medicines for infants with colic.</p> <p>Conclusion</p> <p>Nigerian mothers are deficient in their knowledge of colic. Self-medication was the most frequently used home-based intervention. Health education would appear necessary to improve parental management of this self-limiting condition.</p

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg