Genetic and genomic analysis of reproduction traits in holstein cattle using SNP chip data and imputed sequence level genotypes.

BACKGROUND: Reproductive performance plays an important role in animal welfare, health and profitability in animal husbandry and breeding. It is well established that there is a negative correlation between performance and reproduction in dairy cattle. This relationship is being increasingly considered in breeding programs. By elucidating the genetic architecture of underlying reproduction traits, it will be possible to make a more detailed contribution to this. Our study followed two approaches to elucidate this area; in a first part, variance components were estimated for 14 different calving and fertility traits, and then genome-wide association studies were performed for 13 reproduction traits on imputed sequence-level genotypes with subsequent enrichment analyses. RESULTS: Variance components analyses showed a low to moderate heritability (h2) for the traits analysed, ranging from 0.014 for endometritis up to 0.271 for stillbirth, indicating variable degrees of variation within the reproduction traits. For genome-wide association studies, we were able to detect genome-wide significant association signals for nine out of 13 analysed traits after Bonferroni correction on chromosome 6, 18 and the X chromosome. In total, we detected over 2700 associated SNPs encircling more than 90 different genes using the imputed whole-genome sequence data. Functional associations were reviewed so far known and potential candidate regions in the proximity of reproduction events were hypothesised. CONCLUSION: Our results confirm previous findings of other authors in a comprehensive cohort including 13 different traits at the same time. Additionally, we identified new candidate genes involved in dairy cattle reproduction and made initial suggestions regarding their potential impact, with special regard to the X chromosome as a putative information source for further research. This work can make a contribution to reveal the genetic architecture of reproduction traits in context of trait specific interactions.

Examining sustained sub-national health system development: experience from the Western Cape province, South Africa, 1994-2016.

Governance and leadership are recognised as central to health system development in low- and middle-income countries, yet few existing studies consider the influence of multi-level governance systems. South Africa is one of many (quasi-)federal states. Provincial governments have responsibility for managing health care delivery within national policy frameworks and norms. The early post-apartheid period saw country-wide efforts to address the apartheid legacy of health system inequity and inefficiency, but health system transformation subsequently stalled in many provinces. In contrast, the Western Cape provincial health department sustained service delivery reform and strengthened management processes over the period 1994-2016. This department can be considered a 'pocket of relative bureaucratic effectiveness' (POE): an organisational entity that, compared to others, is relatively effective in carrying out its functions in pursuit of the public good. This paper considers what factors enabled the development of the Western Cape health system in the period 1994-2016. Two phases of data collection entailed document review, participatory workshops, 43 in-depth interviews with purposively selected key informants from inside and outside the Western Cape, and a structured survey testing initial insights (response rate 42%). Analysis included triangulation across data sets, comparison between the Western Cape and other provincial experience and deeper reflection on these experiences drawing on POE theory and public administration literature. The analysis highlights the Western Cape experience of stable and astute sub-national governance and leadership and the deepening of administrative and technical capacity over time - within a specific provincial historical and political economy context that sustained the separation of political and administrative powers. Multi-level governance systems can create the space for sub-national POEs to emerge in their mediation of wider political economy forces, generating spaces for skilled reform leaders to act in the public interest, support the emergence of distributed leadership and develop robust management processes.

The Meso-Level in Quality Improvement: Perspectives From a Maternal-Neonatal Health Partnership in South Africa.

BACKGROUND: Sustained implementation of facility-level quality improvement (QI) processes, such as plan-do-study-act cycles, requires enabling meso-level environments and supportive macro-level policies and strategies. Although this is well recognised, there is little systematic empirical evidence on roles and capacities, especially at the immediate meso-level of the system, that sustain QI strategies at the frontline. METHODS: In this paper we report on qualitative research to characterize the elements of a quality and outcome-oriented meso-level, focused on sub/district health systems (DHSs), conducted within a multi-level initiative to improve maternal-newborn health (MNH) in three provinces of South Africa. Drawing on the embedded experience and tacit knowledge of core project partners, obtained through in-depth interviews (39) and project documentation, we analysed thematically the roles, capacities and systems required at the meso-level for sustained QI, and experiences with strengthening the meso-level. RESULTS: Meso-level QI roles identified included establishing and supporting QI systems and strengthening delivery networks. We propose three elements of system capacity as enabling these meso-level roles: (1) leadership stability and capacity, (2) the presence of formal mechanisms to coordinate service delivery processes at sub-district and district levels (including governance, referral and outreach systems), and (3) responsive district support systems (including quality oriented human resource, information, and emergency medical services [EMS] management), embedded within supportive relational eco-systems and appropriate decision-space. While respondents reported successes with system strengthening, overall, the meso-level was regarded as poorly oriented to and even disabling of quality at the frontline. CONCLUSION: We argue for a more explicit orientation to quality and outcomes as an essential district and sub-district function (which we refer to as meso-level stewardship), requiring appropriate structures, processes, and capacities.

Responsive public health doctoral education: experiences and reflections from a School of Public Health in South Africa.

Institutional capacity for doctoral training is key to addressing the complex challenges facing the global south. In the context of the need for skilled knowledge workers in health systems and growing demand for doctoral places, we reflect on the evolution of a public health doctoral programme in a South African School of Public Health. Through this case, we aim to contribute to wider debates on the form and content of emerging public health doctoral programmes in South Africa and the African continent. Drawing on a multi-level framework of 'curriculum responsiveness' we consider responsive public health doctoral education as simultaneously engaging macro-social, institutional/cultural, disciplinary and individual learning imperatives. We assess the responsiveness of the doctoral programme against these elements, describing the growth, institutional context and systems and pedagogical strategies introduced over the last decade, and areas for further development. We conclude by proposing the multi-level capacities required for responsive public health doctoral education. We highlight the need for diversified curricula (including professional doctorates) that support a wider set of graduate attributes and career trajectories beyond academia, greater investment in doctoral infrastructures within higher education institutions, and disciplinary practices and pedagogies that centre epistemic access and justice.

Mendelian randomization analysis of 34,497 German Holstein cows to infer causal associations between milk production and health traits.

BACKGROUND: Claw diseases and mastitis represent the most important health issues in dairy cattle with a frequently mentioned connection to milk production. Although many studies have aimed at investigating this connection in more detail by estimating genetic correlations, they do not provide information about causality. An alternative is to carry out Mendelian randomization (MR) studies using genetic variants to investigate the effect of an exposure on an outcome trait mediated by genetic variants. No study has yet investigated the causal association of milk yield (MY) with health traits in dairy cattle. Hence, we performed a MR analysis of MY and seven health traits using imputed whole-genome sequence data from 34,497 German Holstein cows. We applied a method that uses summary statistics and removes horizontal pleiotropic variants (having an effect on both traits), which improves the power and unbiasedness of MR studies. In addition, genetic correlations between MY and each health trait were estimated to compare them with the estimates of causal effects that we expected. RESULTS: All genetic correlations between MY and each health trait were negative, ranging from - 0.303 (mastitis) to - 0.019 (digital dermatitis), which indicates a reduced health status as MY increases. The only non-significant correlation was between MY and digital dermatitis. In addition, each causal association was negative, ranging from - 0.131 (mastitis) to - 0.034 (laminitis), but the number of significant associations was reduced to five nominal and two experiment-wide significant results. The latter were between MY and mastitis and between MY and digital phlegmon. Horizontal pleiotropic variants were identified for mastitis, digital dermatitis and digital phlegmon. They were located within or nearby variants that were previously reported to have a horizontal pleiotropic effect, e.g., on milk production and somatic cell count. CONCLUSIONS: Our results confirm the known negative genetic connection between health traits and MY in dairy cattle. In addition, they provide new information about causality, which for example points to the negative energy balance mediating the connection between these traits. This knowledge helps to better understand whether the negative genetic correlation is based on pleiotropy, linkage between causal variants for both trait complexes, or indeed on a causal association.

Accuracy of Digital Orthodontic Treatment Planning: Assessing Aligner-Directed Tooth Movements and Exploring Inherent Intramaxillary Side Effects.

Background: The attainment of precise posterior occlusion alignment necessitates a deeper understanding of the clinical efficacy of aligner therapy. This study aims to determine whether the treatment goals defined in the virtual planning of aligner therapy are effectively implemented in clinical practice, with a particular focus on the influence of distalization distances on potential vertical side effects. Methods: In this retrospective, non-interventional investigation, a cohort of 20 individuals undergoing Invisalign® treatment was examined. Pre- and post-treatment maxillary clinical and ClinCheck® casts were superimposed utilizing a surface-surface matching algorithm on palatal folds, median palatine raphe, and unmoved teeth as the stable references. The effectivity of planned versus clinical movements was evaluated. Groupings were based on distalization distances, planned vertical movements, and Class II elastic prescription. Statistics were performed with a two-sample t-test and p-value < 0.05. Results: Clinically achieved distalization was significantly lower than virtually planned distalization, regardless of additional vertical movements, where a lack of implementation was contingent upon the extent of distalization, with no mitigating effects observed with the application of Class II elastics. Intriguingly, no adverse vertical side effects were noted; however, the intended intrusions or extrusions, as per the therapeutic plans, remained unattainable regardless of the magnitude of distalization. Conclusions: These findings underscore the imperative for future investigations to delve deeper into the intricacies surrounding translational mesio-distal and vertical movements, thereby enhancing predictability within orthodontic practice. To facilitate successful clinical implementation of vertical and translational movements via aligners, the incorporation of sliders emerges as a promising strategy for bolstering anchorage reinforcement.

Every loaf of bread is political - Reflections on collective care responses to Covid-19 in Cape Town.

Feminist perspectives on care have demonstrated how capitalism undervalues care work. The Covid-19 pandemic highlighted this further, as systems of production and social reproduction became destabilized globally. In many countries, the formal pandemic response fell short of attending to the daily, fundamental care needs of people living through the crisis, especially those compromised by the socio-economic effects of the pandemic. These needs were often attended to at the community level. This article explores a community-led network of care, known as CANs, that emerged in response to the pandemic in Cape Town. It makes three overarching observations. The first is that community-led responses were characterised by a push towards the collectivisation of care work. The second is that this enabled emergent strategies and relational practices of care, centring notions of solidarity, inter-dependence and horizontal exchange of resources and knowledge. Finally, we observed that, although the devaluation of care work limited the recognition and material support extended to CANs, opportunities to re-politicise care work as resistance work emerged. These represent a prefigurative moment in which alternative logics and strategies can transform the vision of our health and care systems, and the notion of community participation in and ownership of those systems.

Genomic dissection of the correlation between milk yield and various health traits using functional and evolutionary information about imputed sequence variants of 34,497 German Holstein cows.

BACKGROUND: Over the last decades, it was subject of many studies to investigate the genomic connection of milk production and health traits in dairy cattle. Thereby, incorporating functional information in genomic analyses has been shown to improve the understanding of biological and molecular mechanisms shaping complex traits and the accuracies of genomic prediction, especially in small populations and across-breed settings. Still, little is known about the contribution of different functional and evolutionary genome partitioning subsets to milk production and dairy health. Thus, we performed a uni- and a bivariate analysis of milk yield (MY) and eight health traits using a set of ~34,497 German Holstein cows with 50K chip genotypes and ~17 million imputed sequence variants divided into 27 subsets depending on their functional and evolutionary annotation. In the bivariate analysis, eight trait-combinations were observed that contrasted MY with each health trait. Two genomic relationship matrices (GRM) were included, one consisting of the 50K chip variants and one consisting of each set of subset variants, to obtain subset heritabilities and genetic correlations. In addition, 50K chip heritabilities and genetic correlations were estimated applying merely the 50K GRM. RESULTS: In general, 50K chip heritabilities were larger than the subset heritabilities. The largest heritabilities were found for MY, which was 0.4358 for the 50K and 0.2757 for the subset heritabilities. Whereas all 50K genetic correlations were negative, subset genetic correlations were both, positive and negative (ranging from -0.9324 between MY and mastitis to 0.6662 between MY and digital dermatitis). The subsets containing variants which were annotated as noncoding related, splice sites, untranslated regions, metabolic quantitative trait loci, and young variants ranked highest in terms of their contribution to the traits` genetic variance. We were able to show that linkage disequilibrium between subset variants and adjacent variants did not cause these subsets` high effect. CONCLUSION: Our results confirm the connection of milk production and health traits in dairy cattle via the animals` metabolic state. In addition, they highlight the potential of including functional information in genomic analyses, which helps to dissect the extent and direction of the observed traits` connection in more detail.

Reactive Eutectic Media for Lignocellulosic Biomass Fractionation.

This study introduces an alternative approach towards lignocellulosic biomass fractionation. For this purpose, reactive eutectic media (REM) based on ammonium formate and different organic acids are investigated, possible products are identified, and the REM are employed for lignin extraction and terminal isolation of cellulose pulp from beech wood. The method promises a considerable process intensification by simultaneous separation of high purity cellulose pulp, lignin isolation as a cationically modified species, and production of value-added chemicals from reaction products of the REM. This study puts a further focus on the generated cellulose pulp and investigates it with respect to surface charge and fiber length.

A combined strategies intervention on the World Health Organization prescribing indicators: A quasi-randomised trial.

BACKGROUND: Irrational medicine use is a global problem that may potentiate antimicrobial resistance. AIM: This study aims to assess prescribing practices and the effect of a prescription audit and feedback coupled with small-group education intervention on prescribing indicators. SETTING: The study was conducted in public-sector healthcare facilities in Eswatini. METHODS: A cluster quasi-randomised controlled study was conducted from 2016 to 2019 using the World Health Organization/ International Network for Rational Use of Drugs (WHO/INRUD) prescribing indicators at baseline, post-intervention and post-follow-up. A 6-month unblinded intervention was tested in 32 healthcare facilities, randomly allocated to intervention (16) and control (16) arms. Prescribing practices were assessed post-intervention, and 6 months after the intervention, through an audit of 100 randomly selected prescriptions from each facility. Comparisons of WHO or INRUD prescribing indicators were conducted using the intention-to-treat analysis at the two times. RESULTS: At baseline, in both arms, rational prescribing standards were met by the number of medicines per prescription and the use of injections. Antibiotic use was above 50% in both arms. After adjustment for baseline antibiotics use, region and level of care, there were no significant differences in all prescribing indicators between the two arms, post-intervention and at 6 months follow-up. CONCLUSION: In a lower middle-income setting with a high prevalence of irrational prescribing practices, a prescription audit, feedback and small-group education intervention had no benefits in improving rational prescribing.Contribution: Multifaceted strategies, strengthening of pharmacy and therapeutics committees, and holistic monitoring of medicine use are recommended to promote rational medicine use.

Mistrust in government and National Health Insurance: A qualitative study of solo private practitioners in Cape Town.

BACKGROUND:  The participation of independent private general practitioners (GPs) is of fundamental importance to the successful implementation of key elements of the proposed National Health Insurance (NHI) reform, notably the contracting units for primary health care (CUPS). This study explored knowledge and perceptions of the NHI reforms of private GPs following the tabling of the NHI Bill in parliament in 2019. METHODS:  An explorative qualitative research methodology was adopted. Using a semi-structured guide, nine solo private GPs, purposefully selected to represent the range of practices in the southern peninsula of Cape Town were interviewed in depth by B.L.P. over the period from January 2021 to March 2022. RESULTS:  The GPs indicated support for the values of greater equity outlined in the NHI proposals. However, they had little engagement on or knowledge of their potential future roles in NHI. Concerns over financial viability and design were underpinned by an overall mistrust in the public sector to implement and manage NHI. CONCLUSION:  The study concurs with previous research that private GPs are broadly in support of the principles of, and are potential allies, in advancing NHI. General practitioners need a platform to share their concerns and contribute as co-designers of NHI reforms. In the interim, steps to increase collaboration between private and public sectors at local and provincial level through, for example, referral processes may help to build the trust that is necessary between the sectors.Contribution: This study foregrounds the role of trust relationships in advancing NHI.

Service delivery interventions to improve maternal and newborn health in low- and middle-income countries: scoping review of quality improvement, implementation research and health system strengthening approaches.

INTRODUCTION: This review explores the characteristics of service delivery-related interventions to improve maternal and newborn health (MNH) in low-and middle-income countries (LMICs) over the last two decades, comparing three common framings of these interventions, namely, quality improvement (QI), implementation science/research (IS/IR), and health system strengthening (HSS). METHODS: The review followed the staged scoping review methodology proposed by Levac et al. (2010). We developed and piloted a systematic search strategy, limited to English language peer-reviewed articles published on LMICs between 2000 and March 2022. Analysis was conducted in two-quantitative and qualitative-phases. In the quantitative phase, we counted the year of publication, country(-ies) of origin, and the presence of the terms 'quality improvement', 'health system strengthening' or 'implementation science'/ 'implementation research' in titles, abstracts and key words. From this analysis, a subset of papers referred to as 'archetypes' (terms appearing in two or more of titles, abstract and key words) was analysed qualitatively, to draw out key concepts/theories and underlying mechanisms of change associated with each approach. RESULTS: The searches from different databases resulted in a total of 3,323 hits. After removal of duplicates and screening, a total of 231 relevant articles remained for data extraction. These were distributed across the globe; more than half (n = 134) were published since 2017. Fifty-five (55) articles representing archetypes of the approach (30 QI, 16 IS/IR, 9 HSS) were analysed qualitatively. As anticipated, we identified distinct patterns in each approach. QI archetypes tended towards defined process interventions (most typically, plan-do-study-act cycles); IS/IR archetypes reported a wide variety of interventions, but had in common evaluation methodologies and explanatory theories; and HSS archetypes adopted systemic perspectives. Despite their distinctiveness, there was also overlap and fluidity between approaches, with papers often referencing more than one approach. Recognising the complexity of improving MNH services, there was an increased orientation towards participatory, context-specific designs in all three approaches. CONCLUSIONS: Programmes to improve MNH outcomes will benefit from a better appreciation of the distinctiveness and relatedness of different approaches to service delivery strengthening, how these have evolved and how they can be combined.

Development of image-based decision support systems utilizing information extracted from radiological free-text report databases with text-based transformers.

OBJECTIVES: To investigate the potential and limitations of utilizing transformer-based report annotation for on-site development of image-based diagnostic decision support systems (DDSS). METHODS: The study included 88,353 chest X-rays from 19,581 intensive care unit (ICU) patients. To label the presence of six typical findings in 17,041 images, the corresponding free-text reports of the attending radiologists were assessed by medical research assistants ("gold labels"). Automatically generated "silver" labels were extracted for all reports by transformer models trained on gold labels. To investigate the benefit of such silver labels, the image-based models were trained using three approaches: with gold labels only (MG), with silver labels first, then with gold labels (MS/G), and with silver and gold labels together (MS+G). To investigate the influence of invested annotation effort, the experiments were repeated with different numbers (N) of gold-annotated reports for training the transformer and image-based models and tested on 2099 gold-annotated images. Significant differences in macro-averaged area under the receiver operating characteristic curve (AUC) were assessed by non-overlapping 95% confidence intervals. RESULTS: Utilizing transformer-based silver labels showed significantly higher macro-averaged AUC than training solely with gold labels (N = 1000: MG 67.8 [66.0-69.6], MS/G 77.9 [76.2-79.6]; N = 14,580: MG 74.5 [72.8-76.2], MS/G 80.9 [79.4-82.4]). Training with silver and gold labels together was beneficial using only 500 gold labels (MS+G 76.4 [74.7-78.0], MS/G 75.3 [73.5-77.0]). CONCLUSIONS: Transformer-based annotation has potential for unlocking free-text report databases for the development of image-based DDSS. However, on-site development of image-based DDSS could benefit from more sophisticated annotation pipelines including further information than a single radiological report. CLINICAL RELEVANCE STATEMENT: Leveraging clinical databases for on-site development of artificial intelligence (AI)-based diagnostic decision support systems by text-based transformers could promote the application of AI in clinical practice by circumventing highly regulated data exchanges with third parties. KEY POINTS: • The amount of data from a database that can be used to develop AI-assisted diagnostic decision systems is often limited by the need for time-consuming identification of pathologies by radiologists. • The transformer-based structuring of free-text radiological reports shows potential to unlock corresponding image databases for on-site development of image-based diagnostic decision support systems. • However, the quality of image annotations generated solely on the content of a single radiology report may be limited by potential inaccuracies and incompleteness of this report.

Eutectic Media Open a Synthetic Route to Oligocitrazinic Acid Fluorophores of Purple Hue.

Under isochoric and solvent-free conditions, the reaction between ammonium formate and citric acid results in a deeply purple reaction product with fluorescent properties. This brings this reaction in the realm of bio-based fluorophores and bottom-up carbon nanodots from citric acid. The reaction conditions are optimized in terms of UV-vis spectroscopic properties and, subsequently, the main reaction product is separated. While the structural analysis does not give any indication for carbon nanodots in a general sense, it points towards the formation of molecular fluorophores that consist of oligomerized citrazinic acid derivatives. Furthermore, EPR spectroscopy reveals the presence of stable free radicals in the product. We hypothesize that such open-shell structures may play a general role in molecular fluorophores from citric acid and are not yet sufficiently explored. Therefore, we believe that analysis of these newly discovered fluorophores may contribute to a better understanding of the properties of fluorophores and CND from citric acid in general.

Intervention in Mothers and Newborns to Reduce Maternal and Perinatal Mortality in 3 Provinces in South Africa Using a Quality Improvement Approach: Protocol for a Mixed Method Type 2 Hybrid Evaluation.

BACKGROUND: The COVID-19 pandemic undermined gains in reducing maternal and perinatal mortality in South Africa. The Mphatlalatsane Initiative is a health system intervention to reduce mortality and morbidity in women and newborns to desired levels. OBJECTIVE: Our evaluation aims to determine the effect of various exposures, including the COVID-19 pandemic, and a system-level, complex, patient-centered quality improvement (QI) intervention (the Mphatlalatsane Initiative) on maternal and neonatal health services at 21 selected South African facilities. The objectives are to determine whether Mphatlalatsane reduces the institutional maternal mortality ratio, neonatal mortality rate, and stillbirth rate (objective 1) and improves patients' experiences (objective 2) and quality of care (objective 3). Objective 4 assesses the contextual and implementation process factors, including the COVID-19 pandemic, that shape Mphatlalatsane uptake and variation. METHODS: This study is an implementation science type 2 hybrid effectiveness, controlled before-and-after design with quantitative and qualitative components. The Mphatlalatsane intervention commenced at the end of 2019. For objective 1, intervention and control facility-level data from the District Health Information System are compared for changes in institutional maternal and neonatal mortality and stillbirth rates and associations with QI, the COVID-19 pandemic, and both. This first analysis includes data from 18 facilities, regardless of their allocation to intervention or comparison, to obtain a general idea of the effect of the COVID-19 pandemic. For objectives 2 to 3, data collectors abstract data from maternal and neonatal records, interview participants, and conduct neonatal facility assessments. For objective 4, interviews, program documentation, surveys, and observations are used to assess how contextual factors at the macro-, meso-, and microlevels explain variation in intervention uptake and outcome. The intervention dose is measured at the microlevel only in the intervention facilities. The study assesses the Mphatlalatsane Initiative from 2020 to 2022. RESULTS: From preliminary analysis, across the 3 provinces, maternal and neonatal deaths increased during the COVID-19 pandemic, whereas stillbirths remained unchanged. Maternal satisfaction with quality of care was >90%. The COVID-19 pandemic severely disrupted the QI teams functioning. However, the QI teams regained their pre-COVID-19 momentum by adapting the QI model, with advisers providing mentoring and support. Variation in adoption at the mesolevel was related to stable and motivated leadership (particularly at the facility level), poor integration into routine processes, and buy-in from senior district managers who were affected by competing priorities. Varying referral and specialist outreach systems, staff availability and development, and service delivery infrastructure are plausible factors in variable outcomes. CONCLUSIONS: Few evaluations rigorously evaluated the effect of health system interventions on improving health services and outcomes. Results will inform the scaling up of successful intervention components and strategies to mitigate the effects of the COVID-19 pandemic or similar emerging epidemics on maternal and neonatal mortality. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42041.

Genomic dominance variance analysis of health and milk production traits in German Holstein cattle.

Genomic analyses commonly explore the additive genetic variance of traits. The non-additive variance, however, is usually small but often significant in dairy cattle. This study aimed at dissecting the genetic variance of eight health traits that recently entered the total merit index in Germany and the somatic cell score (SCS), as well as four milk production traits by analysing additive and dominance variance components. The heritabilities were low for all health traits (between 0.033 for mastitis and 0.099 for SCS), and moderate for the milk production traits (between 0.261 for milk energy yield and 0.351 for milk yield). For all traits, the contribution of dominance variance to the phenotypic variance was low, varying between 0.018 for ovarian cysts and 0.078 for milk yield. Inbreeding depression, inferred from the SNP-based observed homozygosity, was significant only for the milk production traits. The contribution of dominance variance to the genetic variance was larger for the health traits, ranging from 0.233 for ovarian cysts to 0.551 for mastitis, encouraging further studies that aim at discovering QTLs based on their additive and dominance effects.

A genomic assessment of the correlation between milk production traits and claw and udder health traits in Holstein dairy cattle.

Claw diseases and mastitis represent the most important disease traits in dairy cattle with increasing incidences and a frequently mentioned connection to milk yield. Yet, many studies aimed to detect the genetic background of both trait complexes via fine-mapping of quantitative trait loci. However, little is known about genomic regions that simultaneously affect milk production and disease traits. For this purpose, several tools to detect local genetic correlations have been developed. In this study, we attempted a detailed analysis of milk production and disease traits as well as their interrelationship using a sample of 34,497 50K genotyped German Holstein cows with milk production and claw and udder disease traits records. We performed a pedigree-based quantitative genetic analysis to estimate heritabilities and genetic correlations. Additionally, we generated GWAS summary statistics, paying special attention to genomic inflation, and used these data to identify shared genomic regions, which affect various trait combinations. The heritability on the liability scale of the disease traits was low, between 0.02 for laminitis and 0.19 for interdigital hyperplasia. The heritabilities for milk production traits were higher (between 0.27 for milk energy yield and 0.48 for fat-protein ratio). Global genetic correlations indicate the shared genetic effect between milk production and disease traits on a whole genome level. Most of these estimates were not significantly different from zero, only mastitis showed a positive one to milk (0.18) and milk energy yield (0.13), as well as a negative one to fat-protein ratio (-0.07). The genomic analysis revealed significant SNPs for milk production traits that were enriched on Bos taurus autosome 5, 6, and 14. For digital dermatitis, we found significant hits, predominantly on Bos taurus autosome 5, 10, 22, and 23, whereas we did not find significantly trait-associated SNPs for the other disease traits. Our results confirm the known genetic background of disease and milk production traits. We further detected 13 regions that harbor strong concordant effects on a trait combination of milk production and disease traits. This detailed investigation of genetic correlations reveals additional knowledge about the localization of regions with shared genetic effects on these trait complexes, which in turn enables a better understanding of the underlying biological pathways and putatively the utilization for a more precise design of breeding schemes.

Early Reflections on Mphatlalatsane, a Maternal and Neonatal Quality Improvement Initiative Implemented During COVID-19 in South Africa.

Despite global progress in reducing maternal and neonatal mortality and stillbirths, much work remains to be done to achieve the Sustainable Development Goals. Reports indicate that coronavirus disease (COVID-19) disrupts the provision and uptake of routine maternal and neonatal health care (MNH) services and negatively impacts cumulative pre-COVID-19 achievements. We describe a multipartnered MNH quality improvement (QI) initiative called Mphatlalatsane, which was implemented in South Africa before and during the COVID-19 pandemic. The initiative aimed to reduce the maternal mortality ratio, neonatal mortality rate, and stillbirth rate by 50% between 2018 and 2022. The multifaceted design comprises QI and other intervention activities across micro-, meso-, and macrolevels, and its area-based approach facilitates patients' access to MNH services. The initiative commenced 6 months pre-COVID-19, with subsequent adaptation necessitated by COVID-19. The initial focus on a plan-do-study-act QI model shifted toward meeting the immediate needs of health care workers (HCWs), the health system, and health care managers arising from COVID-19. Examples include providing emotional support to staff and streamlining supply chain management for infection control and personal protection materials. As these needs were addressed, Mphatlalatsane gradually refocused HCWs' and managers' attention to recognize the disruptions caused by COVID-19 to routine MNH services. This gradual reprioritization included the development of a risk matrix to help staff and managers identify specific risks to service provision and uptake and develop mitigating measures. Through this approach, Mphatlalatsane led to an optimization case using existing resources rather than requesting new resources to build an investment case, with a responsive design and implementation approach as the cornerstone of the initiative. Further, Mphatlalatsane demonstrates that agile and context-specific responses to crises such as the COVID-19 pandemic can mitigate such threats and maintain interventions to improve MNH services.

Expressions of actor power in implementation: a qualitative case study of a health service intervention in South Africa.

BACKGROUND: Implementation frameworks and theories acknowledge the role of power as a factor in the adoption (or not) of interventions in health services. Despite this recognition, there is a paucity of evidence on how interventions at the front line of health systems confront or shape existing power relations. This paper reports on a study of actor power in the implementation of an intervention to improve maternal, neonatal and child health care quality and outcomes in a rural district of South Africa. METHODS: A retrospective qualitative case study based on interviews with 34 actors in three 'implementation units' - a district hospital and surrounding primary health care services - of the district, selected as purposefully representing full, moderate and low implementation of the intervention, some three years after it was first introduced. Data are analysed using Veneklasen and Miller's typology of the forms of power - namely 'power over', 'power to', 'power within' and 'power with'. RESULTS: Multiple expressions of actor power were evident during implementation and played a plausible role in shaping variable implementation, while the intervention itself acted to change power relations. As expected, a degree of buy-in of managers (with power over) in implementation units was necessary for the intervention to proceed. Beyond this, the ability to mobilise collective action (power with), combined with support from champions with agency (power within) were key to successful implementation. However, local empowerment may pose a threat to hierarchical power (power over) at higher levels (district and provincial) of the system, potentially affecting sustainability. CONCLUSIONS: A systematic approach to the analysis of power in implementation research may provide insights into the fate of interventions. Intervention designs need to consider how they shape power relations, especially where interventions seek to widen participation and responsiveness in local health systems.

Working Towards Inclusive, Socially Accountable and Resilient Community Health Systems: An Introduction to a Special Issue.

This editorial introduces the eleven papers in the special issue titled: The multiple lenses on the community health system: implications for research and action. Our editorial begins by describing the collaboration that led to the special issue, and then gives an overview of the contents of the special issue, which include two framing papers and nine empirical contributions from researchers in Zambia, Tanzania, Sweden, South Africa, India, and Australia. We conclude by considering how these papers collectively speak to the theme of resilience.