Designing a "good life" for livestock: Could gene editing improve farm animal welfare in low- and middle- income countries?

Gene editing's successful application to benefit farm animals' welfare is unlikely in the short to medium term, particularly in low- and middle-income countries (LMICs), given the high costs and low rates of success to date in research settings.Reasons: 1. Gene editing is biased toward outcomes that can be easily measured and assessed. More complex traits associated with animal welfare such as behavior or condition are less likely to be targeted using gene editing.  2. Gene editing has been designed for use in vertically integrated production systems as livestock breeding is centralized and breeds themselves are highly standardised in these systems. Many LMICs lack vertically integrated production systems, have higher numbers of smallholder farmers, lack investment by companies and NGOs to promote these technologies, lack gene editing researchers, and have limited local support for biotechnology research and training.Potential downsides of gene editing: 1. Where the intensification of livestock production is growing, gene editing is likely to further accelerate intensification and disadvantage farmers relying on less intensive production systems. 2. Genetic diversity across traditional breeds is valuable and should be maintained. It is not clear how gene editing could affect this diversity.There may be specific applications that could lead to improvements in animal welfare in certain LMICs, for example: 1. Using gene editing to bias sex ratios could be particularly valuable in India, given the country's extensive dairy industry. 2. Sex selection in layer hens in Egypt, given hens there are raised in an increasingly vertically integrated production system. 3. Producing polled cattle and eliminating the need for mechanical dehorning as currently occurs in many locales.Many farm animal welfare issues in LMICs are less likely to be addressed through applications of gene editing as opposed to lower technological measures such as better access to veterinary services, better management practices, improved biosecurity, and poverty reduction

Technology Translation and Synthesis: A Conceptual Framework for Critiquing Determinism in the Development Project

This thesis constructs a theoretical framework which critiques the legitimacy of technology transfer for the purposes of development. Under the auspices of the development project, technology transfer has involved the introduction of technology into so-called developing societies in the hope of leapfrogging them toward modernity. This process embodies a deterministic definition of technology that sees it as an inherently objective and rational process, mapping the ideas of Western science. Hence, all technological and social change is expected to follow a linear progression from pre-modern to modern, and developing to developed, respectively. In contrast, philosophers of technology have argued that technology has a cultural dimension which permits multiple avenues of change. This definition incorporates a dialogue between technology and society, whereby technologies are reinterpreted and imbued with culturally specific meanings by the adopting societies. The culturally contingent nature of these meanings entails that they are not necessarily transferable between cultures. Rather, technology must be translated. Conceptually, technology translation requires that aspects of the donor and recipient cultures are intertwined, producing a novel set of hybridised meanings. I argue that this process occurs primarily through the mode of synthesis - an emergent process whose outcomes are not predictable based solely on a priori knowledge of the interacting cultures. These ideas are tested in case studies arising from Indian agriculture. Indian agriculture has a long history of external agricultural influence in the shape of European colonialism, the Green Revolution and the more recent Gene Revolution. The results support the idea that both technology transfer and synthesis have occurred in Indian agriculture following the adoption of new technologies. Development agencies must revise their simplistic notion of technology by acknowledging the centrality of culture as part of technology, therefore, if they wish to ensure greater success in the future

Precision Farming by Cotton Producers in Eleven Southern States: Results from the 2005 Southern Precision Farming Survey

Precision Farming by Cotton Producers in Eleven Southern States: Results from the 2005 Southern Precision Farming Surveycotton, precision farming, survey, Agribusiness, Farm Management, Production Economics, Research and Development/Tech Change/Emerging Technologies,

SAEM Response to the National Institutes of Health request for information: Future directions in violence against women research

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Identifying factors which influence eating disorder risk during behavioral weight management: A consensus study

This study aimed to understand clinician, researcher and consumer views regarding factors which influence eating disorder (ED) risk during behavioral weight management, including individual risk factors, intervention strategies and delivery features. Eighty-seven participants were recruited internationally through professional and consumer organizations and social media and completed an online survey. Individual characteristics, intervention strategies (5-point scale) and delivery features (important/unimportant/unsure) were rated. Participants were mostly women (n = 81), aged 35-49 y, from Australia or United States, were clinicians and/or reported lived experience of overweight/obesity and/or ED. There was agreement (64% to 99%) that individual characteristics were relevant to ED risk, with history of ED, weight-based teasing/stigma and weight bias internalization having the highest agreement. Intervention strategies most frequently rated as likely to increase ED risk included those with a focus on weight, prescription (structured diets, exercise plans) and monitoring strategies, e.g., calorie counting. Strategies most frequently rated as likely to decrease ED risk included having a health focus, flexibility and inclusion of psychosocial support. Delivery features considered most important were who delivered the intervention (profession, qualifications) and support (frequency, duration). Findings will inform future research to quantitatively assess which of these factors predict eating disorder risk, to inform screening and monitoring protocols

Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants.

Context: Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Design: Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Setting: Hospital antenatal clinics. Participants: In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Interventions: 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. Main Outcome Measure: 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele]. Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P < 0.004]. In contrast, rs10741657 (CYP2R1) (β = -5.2 nmol/L; 95% CI, -8.2 to -2.2 nmol/L; P = 0.001) and rs2282679 (GC) (β = 4.2 nmol/L; 95% CI, 0.9 to 7.5 nmol/L; P = 0.01) were associated with achieved 25(OH)D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Conclusions: Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity

The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study

Background The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. Methods This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). Findings Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61–83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5–8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00–2·41) for CFS 3–4, 1·83 (1·15–2·91) for CFS 5–6, and 2·39 (1·50–3·81) for CFS 7–9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63–2·38) for CFS 3–4, 1·62 (0·81–3·26) for CFS 5–6, and 3·12 (1·56–6·24) for CFS 7–9. Interpretation In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19

Resistance to the CCR5 Inhibitor 5P12-RANTES Requires a Difficult Evolution from CCR5 to CXCR4 Coreceptor Use

Viral resistance to small molecule allosteric inhibitors of CCR5 is well documented, and involves either selection of preexisting CXCR4-using HIV-1 variants or envelope sequence evolution to use inhibitor-bound CCR5 for entry. Resistance to macromolecular CCR5 inhibitors has been more difficult to demonstrate, although selection of CXCR4-using variants might be expected. We have compared the in vitro selection of HIV-1 CC1/85 variants resistant to either the small molecule inhibitor maraviroc (MVC) or the macromolecular inhibitor 5P12-RANTES. High level resistance to MVC was conferred by the same envelope mutations as previously reported after 16–18 weeks of selection by increasing levels of MVC. The MVC-resistant mutants were fully sensitive to inhibition by 5P12-RANTES. By contrast, only transient and low level resistance to 5P12-RANTES was achieved in three sequential selection experiments, and each resulted in a subsequent collapse of virus replication. A fourth round of selection by 5P12-RANTES led, after 36 weeks, to a “resistant” variant that had switched from CCR5 to CXCR4 as a coreceptor. Envelope sequences diverged by 3.8% during selection of the 5P12-RANTES resistant, CXCR4-using variants, with unique and critical substitutions in the V3 region. A subset of viruses recovered from control cultures after 44 weeks of passage in the absence of inhibitors also evolved to use CXCR4, although with fewer and different envelope mutations. Control cultures contained both viruses that evolved to use CXCR4 by deleting four amino acids in V3, and others that maintained entry via CCR5. These results suggest that coreceptor switching may be the only route to resistance for compounds like 5P12-RANTES. This pathway requires more mutations and encounters more fitness obstacles than development of resistance to MVC, confirming the clinical observations that resistance to small molecule CCR5 inhibitors very rarely involves coreceptor switching