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A number of inherited ataxias is known in humans, with more than 250 loci implicated, most of which are included in human ataxia screening panels. Anecdotally, cases of ataxia in the Norwegian elkhound black have been known for the last 40 years. Affected puppies from three litters were clinically and neurologically examined, and postmortem samples were collected for morphological studies, including ultrastructural analyses. The puppies displayed vestibulocerebellar neurological signs and had degenerative histopathological alterations in cerebellum and brain stem. Three affected dogs, each from different litters, as well as both parents and one healthy littermate from each litter, were whole genome sequenced. Through variant calling we discovered a disease-associated 1 bp deletion in HACE1 (CFA12), resulting in a frameshift at codon 333 and a premature stop codon at codon 366. The perfect association combined with the predicted significant molecular effect, strongly suggest that we have found the causative mutation for Norwegian elkhound black ataxia. We have identified a novel candidate gene for ataxia where dogs can serve as a spontaneous model for improved understanding of ataxia, also in human.

[This corrects the article DOI: 10.1371/journal.pone.0225357.].

Despite a growing body of evidence concerning accelerated organic degradation at archaeological sites, there have been few follow-up investigations to examine the status of the remaining archaeological materials in the ground. To address the question of archaeo-organic preservation, we revisited the Swedish, Mesolithic key-site Agerod and could show that the bone material had been subjected to an accelerated deterioration during the last 75 years, which had destroyed the bones in the areas where they had previously been best preserved. To understand why this has happened and to quantify and qualify the extent of the organic degradation, we here analyse the soil chemistry, bone histology, collagen preservation and palaeobotany at the site. Our results show that the soil at Agerod is losing, or has already lost, its preservative and buffering qualities, and that pH-values in the still wet areas of the site have dropped to levels where no bone preservation is possible. Our results suggest that this acidification process is enhanced by the release of sulphuric acid as pyrite in the bones oxidizes. While we are still able to find well-preserved palaeobotanical remains, they are also starting to corrode through re-introduced oxygen into the archaeological layers. While some areas of the site have been more protected through redeposited soil on top of the archaeological layers, all areas of Agerod are rapidly deteriorating. Lastly, while it is still possible to perform molecular analyses on the best-preserved bones from the most protected areas, this opportunity will likely be lost within a few decades. In conclusion, we find that if we, as a society, wish to keep this valuable climatic, environmental and cultural archive, both at Agerod and elsewhere, the time to act is now and if we wait we will soon be in a situation where this record will be irretrievably lost forever.

Background Readmission to hospital is frequent among older patients and reported as a post-discharge adverse outcome. The effect of treatment in a geriatric ward for acutely admitted older patients on mortality and function is well established, but less is known about the possible influence of such treatment on the risk of readmission, particularly in the oldest and most vulnerable patients. Our aim was to assess the risk for early readmission for multimorbid patients > 75 years treated in a geriatric ward compared to medical wards and to identify risk factors for 30-day readmissions. Methods Prospective cohort study of patients acutely admitted to a medical department at a Norwegian regional hospital. Eligible patients were community-dwelling, multimorbid, receiving home care services, and aged 75+. Patients were consecutively included in the period from 1 April to 31 October 2012. Clinical data were retrieved from the referral letter and medical records. Results We included 227 patients with a mean (SD) age of 86.0 (5.7) years, 134 (59%) were female and 59 (26%) were readmitted within 30 days after discharge. We found no statistically significant difference in readmission rate between patients treated in a geriatric ward versus other medical wards. In adjusted Cox proportional hazards regression analyses, lower age (hazard ratio (95% confidence interval) 0.95 (0.91–0.99) per year), female gender (2.17 (1.15–4.00)) and higher MMSE score (1.03 (1.00–1.06) per point) were significant risk factors for readmission. Conclusions Lower age, female gender and higher cognitive function were the main risk factors for 30-day readmission to hospital among old patients with multimorbidity. We found no impact of geriatric care on the readmission rate.

Background and aimThe Helping Babies Breathe program gave major reductions in perinatal mortality in Tanzania from 2009 to 2012. We aimed to study whether this effect was sustained, and whether resuscitation skills changed with continued frequent training.MethodsWe analysed prospective data covering all births (n = 19,571) at Haydom Lutheran Hospital in Tanzania from July 2013 -June 2018. Resuscitation training was continued during this period. All deliveries were monitored by an observer recording the timing of events and resuscitation interventions. Heart rate was recorded by dry-electrode ECG and bag-mask-ventilation by sensors attached to the resuscitator device. We analyzed changes over time in outcomes, use of resuscitation interventions and performance of resuscitation using binary regression models with the log-link function to obtain adjusted relative risks.ResultsWith introduction of user fees for deliveries since 2014, the number of deliveries decreased by 30% from start to the end of the five-year period. An increase in low heart rate at birth and need for bag-mask-ventilation indicate a gradual selection of more vulnerable newborns delivered in the hospital over time. Despite this selection, newborn deaths ConclusionThe reduction in 24-hour newborn mortality after introduction of Helping Babies Breathe was maintained, and a further decrease over the five-year period was evident when analyses were adjusted for vulnerability of the newborns. Perinatal survival and performance of ventilation were significantly improved.

Background Studies of parents’ psychological well-being in single-family rooms in neonatal intensive care units have shown conflicting results. Aims To compare emotional distress in the form of depression, anxiety, stress and attachment scores among parents of very preterm infants cared for in a single-family rooms unit vs an open bay unit. Study design Prospective survey design. Subject Parents (132) of 77 infants born at 28 0/7–32 0/7 weeks of gestation in the two units. Outcome measures Duration of parental presence was recorded. Scores for depression (The Edinburgh Postnatal Depression Scale), anxiety (The State–Trait–Anxiety Inventory, Short Form Y), stress (The Parent Stressor Scale: neonatal intensive care unit questionnaire and The Parenting Stress Index—short form) and attachment (Maternal Postnatal Attachment Scale) measured 14 days after delivery, at discharge, expected term date and four months post-term. Results Parents were present 21 hours/day in the single-family room unit vs 7 hours/day in the Open bay unit. Ninety-three percent of the fathers in the single-family rooms unit were present more than 12 hours per day during the first week. Mothers in the single-family rooms had a significantly lower depression score -1.9 (95% CI: -3.6, -0.1) points from birth to four months corrected age compared to mothers in the Open bay unit, and 14% vs 52% scored above a cut-off point considered being at high risk for depression (p

Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].

Background Approximately 40,000 newborns die each year in Tanzania. Regional differences in outcome are common. Reviewing current local data, as well as defining potential causal pathways leading to death are urgently needed, before targeted interventions can be implemented Objective To describe the clinical characteristics and potential causal pathways contributing to newborn death and determine the presumed causes of newborn mortality within seven days, in a rural hospital setting. Methods Prospective observational study of admitted newborns born October 2014–July 2017. Information about labour/delivery and newborn management/care were recorded on data collection forms. Causes of deaths were predominantly based on clinical diagnosis. Results 671 were admitted to a neonatal area. Reasons included prematurity n = 213 (32%), respiratory issues n = 209 (31%), meconium stained amniotic fluid with respiratory issues n = 115 (17%) and observation for < 24 hours n = 97 (14%). Death occurred in 124 infants. Presumed causes were birth asphyxia (BA) n = 59 (48%), prematurity n = 19 (15%), presumed sepsis n = 19 (15%), meconium aspiration syndrome (MAS) n = 13 (10%) and congenital abnormalities n = 14 (11%). More newborns who died versus survivors had oxygen saturation

ObjectivesTo identify factors associated with QOL in carers of persons with young-onset Alzheimer's (AD) and frontotemporal dementia (FTD) and explore development in QOL over a two-year period.MethodsEighty-eight family carers of community-dwelling people with young-onset AD (n = 50) and FTD (n = 38) recruited from Nordic memory clinics. Carer QOL was assessed using the Quality of Life-Alzheimer's Disease questionnaire. Carer burden was assessed by the Relatives' Stress scale and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. Factors associated with QOL in YOD and development in QOL over time were explored with growth mixture model trajectories and mixed model analyses.ResultsWe identified two carer groups of persons with YOD following trajectories with better (n = 53) versus poorer (n = 30) QOL. Carers who reported more burden at baseline had greater odds of belonging to the poorer QOL group (OR 1.1 (1.0-1.2), p = 0.004). Analyses of the development in QOL showed a significant decline in QOL-AD scores among the AD-carers from baseline to two-year follow-up (p = 0.044), while the score remained stable among the FTD-carers. The FTD-carer group had significantly higher mean QOL-AD scores at one- and two-year follow-up (p = 0.022 and 0.045, respectively). However, the difference between the two groups regarding time trend was non-significant. Poorer QOL was associated with increased carer burden (p = 0.01), more depressive symptoms (p = 0.024), and being male carer (p = 0.038).ConclusionHigher care burden, more depressive symptoms, and being a male carer was associated with poorer QOL in family carers for persons with YOD. Carers of persons with AD may experience greater challenges in preserving QOL compared to carers of persons with FTD.

Introduction: Scandinavian countries have traditionally had a low prevalence of resistant organisms, but have in recent years experienced a change in their epidemiology. We aim to describe the epidemiology of carbapenemase-producing organisms (CPOs), vancomycin-resistant enterococci (VRE) and methicillin-resistant S. aureus (MRSA) in Norway, measure the importance of infections contracted abroad, and assess the morbidity and mortality associated with these resistant bacteria in Norway. Methods and materials: We used data from the Norwegian surveillance system for communicable diseases covering all findings of the selected resistant bacteria including both infections and colonisation, in the period 2006–2017. Annual trends were assessed using negative binomial regression. For MRSA, we were able to calculate the Morisita-Horn index and transmission numbers following importation in order to assess the effect this had on further domestic transmission. Results: The incidence rates (per 100,000 personyears) of the three groups of resistant bacteria have increased during the period. In 2017 the incidence rates were 0.82 for CPOs, 7.09 for VRE and 43.8 for MRSA. 81% of CPO cases were diagnosed in hospitals, but 73% were infected abroad. Most VRE cases were infected in Norwegian hospitals, 85% were associated with hospitals outbreaks. MRSA was predominantly diagnosed in the community, only 21% were diagnosed in hospitals. Of all MRSA cases, 35% were infected in other countries. Most MRSA spa-types were not identified again after introduction, resulting in a transmission of MRSA equivalent to a mean of 0.30 persons infected from each spa-type identified (range: 0–22). The proportion of infections among all notified cases within each diagnose was 44% for MRSA, 9% for VRE and 45% for CPOs. Among persons notified with bacteraemia, the 30 days all-cause mortality were 20%, 16% and 50% for MRSA, VRE and CPOs respectively. Discussion: The incidence rates of CPOs, VRE and MRSA in Norway are low, but increasing. The continuing increase of notified resistant bacteria highlights the need for a revision of existing infection prevention and control guidelines. © 2019 Elstrøm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

miRNAs are an important class of small non-coding RNAs, which play a versatile role in gene regulation at the post-transcriptional level. Expression of miRNAs is often deregulated in human cancers.We analyzed small RNA massive parallel sequencing data from 50 locally advanced breast cancers aiming to identify novel breast cancer related miRNAs. We successfully predicted 10 novel miRNAs, out of which 2 (hsa-miR-nov3 and hsa-miR-nov7) were recurrent. Applying high sensitivity qPCR, we detected these two microRNAs in 206 and 214 out of 223 patients in the study from which the initial cohort of 50 samples were drawn. We found hsa-miR-nov3 and hsa-miR-nov7 both to be overexpressed in tumor versus normal breast tissue in a separate set of 13 patients (p=0.009 and p=0.016, respectively) from whom both tumor tissue and normal tissue were available. We observedhsa-miR-nov3to be expressed at higher levels in ER-positive compared to ER-negative tumors (p=0.037). Further stratifications revealed particularly low levels in the her2-like and basal-like cancers compared to other subtypes (p=0.009 and 0.040, respectively).We predicted target genes for the 2 microRNAs and identified inversely correlated genes in mRNA expression array data available from 203 out of the 223 patients. Applying the KEGG and GO annotations to target genes revealed pathways essential to cell development, communication and homeostasis.Although a weak association between high expression levels ofhsa-miR-nov7and poor survival was observed, this did not reach statistical significance.hsa-miR-nov3expression levels had no impact on patient survival.

Second-generation mammalian target of rapamycin (mTOR) inhibitors such as CC-223 may have theoretical advantages over first-generation drugs by inhibiting TOR kinase in mTOR complex 1 (mTORC1) and 2 (mTORC2), potentially improving clinical efficacy for well-differentiated neuroendocrine tumors (NET).Enrolled patients had metastatic, well-differentiated NET of non-pancreatic gastrointestinal or unknown origin, with/without carcinoid symptoms, had failed ≥1 systemic chemotherapy, and were taking a somatostatin analog (SSA). Oral once-daily CC-223 was administered in 28-day cycles starting at 45 mg (n = 24), with a subsequent cohort starting at 30 mg (n = 23). Objectives were to evaluate tolerability, preliminary efficacy, and pharmacokinetic and biomarker profiles of CC-223. Forty-seven patients completed the study, with mean treatment duration of 378 days and mean dose of 26 mg; 26% of patients remained on the starting dose. Most frequent grade ≥3 toxicities were diarrhea (38%), fatigue (21%), and stomatitis (11%). By investigator, 3 of 41 evaluable patients (7%) showed partial response (PR) and 34 (83%) had stable disease (SD) for a disease control rate (DCR) of 90% (95% confidence interval [CI] 76.9-97.3%). Duration of PR was 125-401 days; median SD duration was 297 days (min-max, 50-1519 days). Median progression-free survival was 19.5 months (95% CI 10.4-28.5 months). Carcinoid symptoms of flushing, diarrhea, or both improved in 50%, 41%, and 39% of affected patients, respectively. For the first time, this study describes that a second-generation mTOR pathway inhibitor can result in highly durable tumor regression and control of NET carcinoid symptoms. The manageable safety profile, high DCR, and durable response, coupled with reduction in carcinoid symptoms refractory to SSA, make CC-223 a promising agent for further development. We thank the patients and their families, and the principal investigator study teams, for enabling this study to complete successfully. We also thank the many support staff at Celgene who were involved in the operational aspects of the study, including Angela Joubert James and Torsten Trowe, who were employees of Celgene at the time of the study. The authors received medical writing assistance from Amy Agbonbhase, PhD, of The Lockwood Group, funded by Celgene Corporation. Sí

It has previously been shown that pretreatment of differentiated human skeletal muscle cells (myotubes) with eicosapentaenoic acid (EPA) promoted increased uptake of fatty acids and increased triacylglycerol accumulation, compared to pretreatment with oleic acid (OA) and palmitic acid (PA). The aim of the present study was to examine whether EPA could affect substrate cycling in human skeletal muscle cells by altering lipolysis rate of intracellular TAG and re-esterification of fatty acids. Fatty acid metabolism was studied in human myotubes using a mixture of fatty acids, consisting of radiolabelled oleic acid as tracer (14C-OA) together with EPA or PA. Co-incubation of myotubes with EPA increased cell-accumulation and incomplete fatty acid oxidation of 14C-OA compared to co-incubation with PA. Lipid distribution showed higher incorporation of 14C-OA into all cellular lipids after co-incubation with EPA relative to PA, with most markedly increases (3 to 4-fold) for diacylglycerol and triacylglycerol. Further, the increases in cellular lipids after co-incubation with EPA were accompanied by higher lipolysis and fatty acid re-esterification rate. Correspondingly, basal respiration, proton leak and maximal respiration were significantly increased in cells exposed to EPA compared to PA. Microarray and Gene Ontology (GO) enrichment analysis showed that EPA, related to PA, significantly changed i.e. the GO terms “Neutral lipid metabolic process” and “Regulation of lipid storage”. Finally, an inhibitor of diacylglycerol acyltransferase 1 decreased the effect of EPA to promote fatty acid accumulation. In conclusion, incubation of human myotubes with EPA, compared to PA, increased processes of fatty acid turnover and oxidation suggesting that EPA may activate futile substrate cycling of fatty acids in human myotubes. Increased TAG—FA cycling may be involved in the potentially favourable effects of long-chain polyunsaturated n-3 fatty acids on skeletal muscle and whole-body energy metabolism. Open Access. Research accepted by PLOS journals is published under a CC BY license. Anyone may reuse the article with proper attribution.

Background Despite the urgent need for new, effective antibiotics, few antibiotics of value have entered the market during the past decades. Therefore, incentives have been developed to stimulate antibiotic R&D. For these incentives to be effective, geographic availability for recently approved antibiotics needs to be better understood. In this study, we analyze geographic availability and market introduction of antibiotics approved between 1999 and 2014. Material and method We identified antibiotics, considered new chemical entities (NCEs) for systemic use approved globally between 1999 and 2014, from national medicine agencies’ lists of approved drugs, and data from the WHO Collaborating Center for Drug Statistics. Geographic availability was mapped using sales data from IQVIA, and analyzed with regards to class, indication, safety, and origin. Results Of the 25 identified NCEs, only 12 had registered sales in more than 10 countries. NCEs with the widest geographic availability had registered sales in more than 70 countries within a ten-year timeframe and 30 countries within a three-year timeframe, spreading across five different geographic regions and three country income classes. Half (52%) of the NCEs had an indication for infections caused by antibiotic- resistant bacteria, little diversity was seen regarding target pathogen and indication. Antibiotics originated from and/or marketed by companies from the US or Europe had greater geographic availability compared to Japanese antibiotics, which seldom reached outside of Asia. For 20 NCEs developers chose to fully or partially sublicense marketing rights to a number of companies of different sizes. Conclusion Our findings show great variation in geographic availability of antibiotics, indicating that availability in multiple regions and country income classes is possible, but rarely seen within a few years of market authorization. Sublicensing agreements between multiple companies was common practice. Moreover, differences were seen between countries regarding benefit/risk evaluations and company behavior. These findings could be a potential source of uncertainties, and create barriers to assure that working antibiotics are developed and made available according to public health needs.

Background Intrapartum Fetal Heart Rate (FHR) monitoring is crucial for the early detection of abnormal FHR, facilitating timely obstetric interventions and thus the potential reduction of adverse perinatal outcomes. We explored midwifery practices of intrapartum FHR monitoring pre and post implementation of a novel continuous automatic Doppler device (the Moyo). Methodology A pre/post observational study among low-risk pregnancies at a tertiary hospital was conducted from March to December 2016. In the pre-implementation period, intermittent monitoring was conducted with a Pinard stethoscope (March to June 2016, n = 1640 women). In the post-implementation period, Moyo was used for continuous FHR monitoring (July-December 2016, n = 2442 women). The primary outcome was detection of abnormal FHR defined as absent, FHR 160bpm. The secondary outcomes were rates of assessment/documentation of FHR, obstetric time intervals and intrauterine resuscitations. Chi-square test, Fishers exact test, t-test and Mann-Whitney U test were used in bivariate analysis whereas binary and multinomial logistic regression were used for multivariate. Results Moyo use was associated with greater detection of abnormal FHR (8.0%) compared with Pinard (1.6%) (p

BACKGROUND:Effective positive pressure ventilation (PPV) of non-breathing newborns is crucial in facilitating cardio-respiratory adaptation at birth. Identifying predictors of death in newborns receiving PPV is important in order to facilitate preventative strategies. OBJECTIVE:The objective of this study was to determine the perinatal predictors of death including the quality of PPV administered among admitted newborns. METHODS:An observational study of admitted newborns who received PPV after birth was conducted. Research assistants observed all deliveries and recorded perinatal events on data collection forms. Measured heart rate (HR) and ventilation parameters were then compared between newborns who died and survivors. RESULTS:Newborns (n = 232) were studied between October 2014 and November 2016. Newborns who died (n = 53) compared to survivors (n = 179) had more fetal heart rate (FHRT) abnormalities (12/53 vs 19/179; p = 0.03); lower initial HR (100 beats/minute from birth (180 vs 149 seconds; p = 0.07). Newborns who died compared to survivors took longer time (14 vs 4 seconds; p = 0.008) and more inflations (7 vs 3; p = 0.006) to achieve an expired volume (Vt) of 6 ml/kg, respectively. Median delivered Vt during the first 60 seconds of PPV was less in newborns who died compared to survivors (5 vs 6 ml/kg; p = 0.12). Newborns who died proceeded to severe encephalopathy (15/31 vs 1/59; p

Background Clinical reasoning is an important topic in healthcare training, assessment, and research. Virtual patients (VPs) are a safe environment to teach, assess and perform research on clinical reasoning and diagnostic accuracy. Our aim was to explore the details of the clinical reasoning process and diagnostic accuracy of undergraduate medical students when working with VPs using a concept mapping tool. Methods Over seven months we provided access to 67 German and 30 English VPs combined with a concept mapping tool to visualize and measure the clinical reasoning process of identifying problems, differential diagnoses, recommended tests and treatment options, and composing a summary statement about a VP. A final diagnosis had to be submitted by the learners in order to conclude the VP scenario. Learners were allowed multiple attempts or could request the correct diagnosis from the system. Results We analyzed 1,393 completed concept maps from 317 learners. We found significant differences between maps with a correct final diagnosis on one or multiple attempts and maps in which learners gave up and requested the solution from the system. These maps had lower scores, fewer summary statements, and fewer problems, differential diagnoses, tests, and treatments. Conclusions The different use patterns and scores between learners who had the correct final diagnosis on one or multiple attempts and those who gave up, indicate that diagnostic accuracy in the form of a correct final diagnosis on the first attempt has to be reconsidered as a sole indicator for clinical reasoning competency. For the training, assessment, and research of clinical reasoning we suggest focusing more on the details of the process to reach a correct diagnosis, rather than whether it was made in the first attempt.

Objective The organization of work has undergone vast transformations over the past four decades in the United States and has had profound impacts on worker health and wellbeing. The profession of commercial truck driving is one of the best examples. Particularly for long-haul truck drivers, changes in work organization have led to disproportionately poor physiological, psychological, and sleep health outcomes. Methods The present study examined disparities in cardiometabolic disease risk among long-haul truck drivers and the general population, and the influence of work organization and sleep in generating these outcomes. Researchers collected survey data from 260 drivers, and blood assay samples from 115 of those drivers, at a large highway truck stop in North Carolina. Comparisons were made for cardiovascular and metabolic risk against the 2011–2012 National Health and Nutrition Examination Survey (NHANES). In addition, logistic regression was used to explore predictive relationships between work organization and sleep and risk for cardiovascular and metabolic disease. Results There were statistically significant mean differences between the long-haul truck driver sample and the NHANES sample for both cardiovascular (3.71 vs. 3.10; p

Globally, the burden of deaths and illness is still unacceptably high at the day of birth. Annually, approximately 300.000 women die related to childbirth, 2.7 million babies die within their first month of life, and 2.6 million babies are stillborn. Many of these fatalities could be avoided by basic, but prompt care, if birth attendants around the world had the necessary skills and competencies to manage life-threatening complications around the time of birth. Thus, the innovative Helping Babies Survive (HBS) and Helping Mothers Survive (HMS) programs emerged to meet the need for more practical, low-cost, and low-tech simulation-based training. This paper provides users of HBS and HMS programs a 10-point list of key implementation steps to create sustained impact, leading to increased survival of mothers and babies. The list evolved through an Utstein consensus process, involving a broad spectrum of international experts within the field, and can be used as a means to guide processes in low-resourced countries. Successful implementation of HBS and HMS training programs require country-led commitment, readiness, and follow-up to create local accountability and ownership. Each country has to identify its own gaps and define realistic service delivery standards and patient outcome goals depending on available financial resources for dissemination and sustainment.