Development of an exercise intervention for the prevention of musculoskeletal shoulder problems after breast cancer treatment : the prevention of shoulder problems trial (UK PROSPER)

Background Musculoskeletal shoulder problems are common after breast cancer treatment. There is some evidence to suggest that early postoperative exercise is safe and may improve shoulder function. We describe the development and delivery of a complex intervention for evaluation within a randomised controlled trial (RCT), designed to target prevention of musculoskeletal shoulder problems after breast cancer surgery (The Prevention of Shoulder Problems Trial; PROSPER). Methods A pragmatic, multicentre RCT to compare the clinical and cost-effectiveness of best practice usual care versus a physiotherapy-led exercise and behavioural support intervention in women at high risk of shoulder problems after breast cancer treatment. PROSPER will recruit 350 women from approximately 15 UK centres, with follow-up at 6 and 12 months. The primary outcome is shoulder function at 12 months; secondary outcomes include postoperative pain, health related quality of life, adverse events and healthcare resource use. A multi-phased approach was used to develop the PROSPER intervention which was underpinned by existing evidence and modified for implementation after input from clinical experts and women with breast cancer. The intervention was tested and refined further after qualitative interviews with patients newly diagnosed with breast cancer; a pilot RCT was then conducted at three UK clinical centres. Discussion The PROSPER intervention incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity; and behavioural strategies to encourage adherence and support exercise behaviour. The final PROSPER intervention is fully manualised with clear, documented pathways for clinical assessment, exercise prescription, use of behavioural strategies, and with guidance for treatment of postoperative complications. This paper adheres to TIDieR and CERT recommendations for the transparent, comprehensive and explicit reporting of complex interventions. Trial registration: International Standard Randomised Controlled Trial Number: ISRCTN 35358984

Effects of two contrasting canopy manipulations on growth and water use of London plane (Platanus x acerifolia) trees

Aims: Two contrasting canopy manipulations were compared to unpruned controls on London plane trees, to determine the effects on canopy regrowth, soil and leaf water relations. Methods: ‘Canopy reduction’, was achieved by removing the outer 30 % length of all major branches and ‘canopy thinning’, by removing 30 % of lateral branches arising from major branches. Results: Total canopy leaf areas recovered within two and three years of pruning for the canopy-thinned and reduced trees respectively. Canopy reduction increased mean leaf size, nitrogen concentration, canopy leaf area density and conserved soil moisture for up to 3 years, whereas canopy thinning had no effects. Another experiment compared more severe canopy reduction to unpruned trees. This produced a similar growth response to the previous experiment, but soil moisture was conserved nearer to the trunk. Analysis of 13C and 18O signals along with leaf water relations and soil moisture data suggested that lower boundary layer conductance within the canopy-reduced trees restricted tree water use, whereas for the canopy-thinned trees the opposite occurred. Conclusions: Only canopy reduction conserved soil moisture and this was due to a combination of reduced total canopy leaf area and structural changes in canopy architecture

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study)

Background Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. Methods A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. Results Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 (<US$16) and not cost-effective. Conclusions Adherence with travoprost was high and not further increased by the intervention. Nevertheless, the study demonstrated that provision of information, tailored to the individual, was inexpensive and able to achieve high patient satisfaction with respect to information about glaucoma medication. Measurement of adherence remains problematic since awareness of study participation may cause a change in participant behaviour

Pacific island regional preparedness for El Niño

The El Niño Southern Oscillation (ENSO) cycle is often blamed for disasters in Pacific island communities. From a disaster risk reduction (DRR) perspective, the challenges with the El Niño part of the ENSO cycle, in particular, are more related to inadequate vulnerability reduction within development than to ENSO-induced hazard influences. This paper analyses this situation, filling in a conceptual and geographic gap in El Niño-related research, by reviewing El Niño-related preparedness (the conceptual gap) for Pacific islands (the geographic gap). Through exploring El Niño impacts on Pacific island communities alongside their vulnerabilities, resiliences, and preparedness with respect to El Niño, El Niño is seen as a constructed discourse rather than as a damaging phenomenon, leading to suggestions for El Niño preparedness as DRR as part of development. Yet the attention which El Niño garners might bring resources to the Pacific region and its development needs, albeit in the short term while El Niño lasts. Conversely, the attention given to El Niño could shift blame from underlying causes of vulnerability to a hazard-centric viewpoint. Instead of focusing on one hazard-influencing phenomenon, opportunities should be created for the Pacific region to tackle wider DRR and development concerns

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10^{-8}; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10^{−10}; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

Environmental effects and individual body condition drive seasonal fecundity of rabbits: identifying acute and lagged processes

The reproduction of many species is determined by seasonally-driven resource supply. But it is difficult to quantify whether the fecundity is sensitive to short- or long-term exposure to environmental conditions such as rainfall that drive resource supply. Using 25 years of data on individual fecundity of European female rabbits, Oryctolagus cuniculus, from semiarid Australia, we investigate the role of individual body condition, rainfall and temperature as drivers of seasonal and long-term and population-level changes in fecundity (breeding probability, ovulation rate, embryo survival). We built distributed lag models in a hierarchical Bayesian framework to account for both immediate and time-lagged effects of climate and other environmental drivers, and possible shifts in reproduction over consecutive seasons. We show that rainfall during summer, when rabbits typically breed only rarely, increased breeding probability immediately and with time lags of up to 10 weeks. However, an earlier onset of the yearly breeding period did not result in more overall reproductive output. Better body condition was associated with an earlier onset of breeding and higher embryo survival. Breeding probability in the main breeding season declined with increased breeding activity in the preceding season and only individuals in good body condition were able to breed late in the season. Higher temperatures reduce breeding success across seasons. We conclude that a better understanding of seasonal dynamics and plasticity (and their interplay) in reproduction will provide crucial insights into how lagomorphs are likely to respond and potentially adapt to the influence of future climate and other environmental change.Konstans Wells, Robert B. O’Hara, Brian D. Cooke, Greg J. Mutze, Thomas A.A. Prowse, Damien A. Fordha

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

\ua9 2021, The Author(s).Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 7 10−8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 7 10−10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukaemia

Cytarabine (AraC) represents the most effective single agent treatment for AML. Nevertheless, overriding AraC resistance in AML remains an unmet medical need. Here we show that the CHK1 inhibitor (CHK1i) GDC-0575 enhances AraC-mediated killing of AML cells both in vitro and in vivo, thus abrogating any potential chemoresistance mechanisms involving DNA repair. Importantly, this combination of drugs does not affect normal long-term hematopoietic stem/progenitors. Moreover, the addition of CHK1i to AraC does not generate de novo mutations and in patients' samples where AraC is mutagenic, addition of CHK1i appears to eliminate the generation of mutant clones. Finally, we observe that persistent residual leukemic cells are quiescent and can become responsive to the treatment when forced into cycle via granulocyte colony-stimulating factor (G-CSF) administration. This drug combination (AraC+CHK1i+G-CSF) will open the doors for a more efficient treatment of AML in the clinic