Liberia health system's journey to long-term recovery and resilience post-Ebola: a case study of an exemplary multi-year collaboration.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict' Liberia is one of the three countries worst hit by the 2014-2016 West Africa Ebola Virus disease (EVD) outbreak, during which it recorded over 10,000 cases, including health workers. Estimates suggest that the non-EVD morbidity and mortality resulting from the collapse of the health system exceeded the direct impact of EVD. Lessons from the outbreak were clear, not only for Liberia but also for the regional and global communities: that building health system resilience through an integrated approach is an investment in population health and wellbeing, as well as economic security and national development. It is therefore no surprise that Liberia made recovery and resilience a national priority from the time the outbreak waned in 2015. The recovery agenda provided the platform for stakeholders to work toward the restoration of the pre-outbreak baseline of health system functions while aiming to build a higher level of resilience, informed by lessons from the Ebola crises. Based on the co-authors' experiences of on-the-ground country-support work, this study sought to provide an overview of the Liberia Health Service Resilience project (2018-2023) funded by KOICA, and propose a set of recommendations for national authorities and donors, derived from the authors' perceptions of best practices and key challenges associated with the project. We used both quantitative and qualitative approaches to generate the data represented in this study by reviewing published and unpublished technical and operational documents, and datasets derived through situational and needs assessments and routine monitoring and evaluation activities. This project has contributed to the implementation of the Liberia Investment Plan for Building a Resilient Health System and the successful response to the COVID-19 outbreak in Liberia. Although limited in scope, the Health Service Resilience project has demonstrated that health system resilience could be operationalized by applying a catchment and integrated approach and encouraging multi-sectoral collaboration, partnership, local ownership, and promoting the Primary Health Care approach. Principles applied in this pilot could guide the operationalization of health system resilience efforts in other resource-limited settings similar to Liberia and beyond.

Identifying legitimacy: Experimental evidence on compliance with authority.

To what extent do individuals' perceptions of legitimacy affect their intrinsic motivations to comply with an authority? Answering this question has critical implications for law enforcement but is challenging because actions or institutions that affect intrinsic motivations typically also affect extrinsic, material ones. To disentangle these, we propose an experimental approach that separately identifies the effect of an authority's costly action to improve enforcement fairness on citizen behavior through both intrinsic and extrinsic channels. In experiment 1, the authority's simple attempt to institute fairer enforcement increases prosocial behavior by 10 to 12 percentage points via the intrinsic channel. A follow-up experiment demonstrates that this is not motivated by citizen attempts to "pay back" authorities. Our findings provide causally credible evidence that an authority's actions can directly shape citizens' behavior by enhancing her legitimacy and have important implications in policy domains where this conflicts with other incentives.

Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity.

Calcitonin-gene-related peptide (CGRP) is a lateral olivocochlear (LOC) efferent neurotransmitter. Depression of sound-driven auditory brainstem response amplitude in CGRP-null mice suggests the potential for endogenous CGRP release to upregulate spontaneous and/or sound-driven auditory nerve (AN) activity. We chronically infused CGRP into the guinea pig cochlea and evaluated changes in AN activity as well as outer hair cell (OHC) function. The amplitude of both round window noise (a measure of ensemble spontaneous activity) and the synchronous whole-nerve response to sound (compound action potential, CAP) were enhanced. Lack of change in both onset adaptation and steady state amplitude of sound-evoked distortion product otoacoustic emission (DPOAE) responses indicated CGRP had no effect on OHCs, suggesting the origin of the observed changes was neural. Combined with results from the CGRP-null mice, these results appear to confirm that endogenous CGRP enhances auditory nerve activity when released by the LOC neurons. However, infusion of the CGRP receptor antagonist CGRP (8-37) did not reliably influence spontaneous or sound-driven AN activity, or OHC function, results that contrast with the decreased ABR amplitude measured in CGRP-null mice.

Effects of bismuth subsalicylate and calcium-ammonium nitrate on ruminal in vitro fermentation of bahiagrass hay with supplemental molasses.

There is a need to increase efficiency of beef production. Decreasing losses of CH4 and improving byproduct utilization are popular strategies. Two feed additives were tested to find potential solutions. Three randomized complete block design experiments were performed using batch culture systems to evaluate the effects of bismuth subsalicylate (BSS) and calcium-ammonium nitrate (CAN) on in vitro ruminal fermentation of bahiagrass hay and supplemental molasses. The first experiment contained four treatments: (1) basal substrate; (2) basal substrate with 0.75% urea (DM basis); (3) basal substrate with 1.2% CAN and 0.38% urea (DM basis); and (4) basal substrate with 2.4% CAN (DM basis). Treatments 2, 3, and 4 were isonitrogenous. The second experiment had a 4 × 3 factorial arrangement of treatments with 4 concentrations of BSS (0.00, 0.33, 0.66, and 1.00%; DM basis) and 3 concentrations of CAN (0.0, 1.2, and 2.4%; DM basis). The third experiment had the following treatments: (1) basal substrate; (2) basal substrate with 0.05% BSS (DM basis); (3) basal substrate with 0.10% BSS (DM basis); and (4) basal substrate with 0.33% BSS (DM basis). For all experiments, basal substrate consisted of Pensacola bahiagrass hay (Paspalum notatum Flüggé; 80% substrate DM) and molasses (20% substrate DM). All data were analyzed using the MIXED procedure of SAS. In Exp. 1, in vitro organic matter (OM) digestibility (IVOMD) was linearly reduced (P < 0.001) with the inclusion of CAN, and CH4, in mmol/g OM fermented, was decreased linearly (P < 0.001). The volatile fatty acid (VFA) profile was not impacted by the inclusion of nonprotein nitrogen (NPN) or CAN (P > 0.05). In Exp. 2, except for CH4 production (P < 0.05), there were no BSS × CAN interactions. Linear reductions in total gas production (P < 0.001), IVOMD (P < 0.001), and total concentration of VFA (P = 0.007) were observed with the inclusion of BSS up to 1%. The inclusion of BSS decreased H2S production in a quadratic manner (P = 0.024). In Exp. 3, IVOMD was not impacted by the inclusion of BSS (P > 0.05); however, production of H2S was linearly decreased (P = 0.004) with the inclusion of BSS up to 0.33%. In conclusion, in vitro fermentation was negatively impacted by the inclusions of BSS, up to 1%, and CAN, up to 2.4%; however, BSS decreased production of H2S when included up to 0.33% without impeding fermentation, while CAN decreased CH4 production.

Effects of nutrient restriction on the metabolic profile of Bos indicus-influenced and B. taurus suckled beef cows.

Recent research from our group demonstrated that Bos indicus-influenced suckled beef cows had greater resilience to withstand nutrient restriction and establish pregnancy compared with B. taurus cows exposed to the same conditions. To further understand these findings, differences in metabolic profile between these same B. indicus-influenced and B. taurus females were explored. Suckled beef cows (n = 134) were enrolled in a completely randomized design with a 2 × 2 factorial arrangement of treatments. On day -21, Angus (AN; Bos taurus) and Brangus (BN; B. indicus-influenced) cows were randomly assigned to 1) a diet that met daily energy maintenance requirements (MAINT), or 2) a diet that restricted intake to 70% of the daily energy maintenance requirements (RESTR). Cows were exposed to an estrus synchronization protocol and received an embryo 7 d after ovulation was pharmacologically induced on day 0. Blood samples were collected on days -21 and 19 to determine circulating concentrations of non-esterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), insulin, glucose, and IGF-1. Pregnancy status after embryo transfer was determined on day 28. As a consequence of the proposed diets, cows in the RESTR diet had less body condition score (BCS) on day 19 (P = 0.008) across breed types. Moreover, BCS change from day -21 to 19 was included as independent covariate into subsequent analyses, allowing for the comparison of breed types under an equivalent level of body reserve mobilization. A breed × diet interaction was observed for plasma insulin (P = 0.03) and IGF-1 (P = 0.04) on day 19, where AN-RESTR cows had less plasma concentrations on day 19 compared with AN-MAINT cows. Diets did not impact (P > 0.10) plasma insulin and IGF-1 concentrations in BN cows. No diet or breed effects were observed in circulating concentrations of NEFA, BHB, and glucose (P > 0.10). Across breed types and nutritional treatment, there was positive linear effect (P ≤ 0.04) of plasma concentrations of insulin and IGF-1 on the probability of pregnancy to fixed-time embryo transfer. In summary, the negative impacts of nutrient restriction on the somatotropic axis, independently of body tissue mobilization, were heightened in Bos taurus females compared with B. indicus-influenced cohorts, which corroborate with the differences observed in fertility between these subspecies.

New Perspectives for Cancer Hazard Evaluation by the Report on Carcinogens: A Case Study Using Read-Across Methods in the Evaluation of Haloacetic Acids Found as Water Disinfection By-Products.

BACKGROUND: Due to the large number of chemicals not yet tested for carcinogenicity but to which people are exposed, the limited number of human and animal cancer studies conducted each year, and the frequent need for a timely response, mechanistic data are playing an increasingly important role in carcinogen hazard identification. OBJECTIVES: To provide a targeted approach to identify relevant mechanistic data in our cancer evaluation of haloacetic acids (HAAs), we used several approaches including systematic review, the 10 key characteristics of carcinogens (KCs), and read-across methods. Our objective in this commentary is to discuss the strengths, limitations, and challenges of these approaches in a cancer hazard assessment. METHODS: A cancer hazard assessment for 13 HAAs found as water disinfection by-products was conducted. Literature searches for mechanistic studies focused on the KCs and individual HAAs. Studies were screened for relevance and categorized by KCs and other relevant data, including chemical properties, toxicokinetics, and biological effects other than KCs. Mechanistic data were organized using the KCs, and strength of evidence was evaluated; this information informed potential modes of action (MOAs) and read-across-like approaches. Three read-across options were considered: evaluating HAAs as a class, as subclass(es), or as individual HAAs (analog approach). DISCUSSION: Because of data limitations and uncertainties, listing as a class or subclass(es) was ruled out, and an analog approach was used. Two brominated HAAs were identified as target (untested) chemicals based on their metabolism and similarity to source (tested) chemicals. In addition, four HAAs with animal cancer data had sufficient evidence for potential listing in the Report on Carcinogens (RoC). This is the first time that the KCs and other relevant data, in combination with read-across principles, were used to support a recommendation to list chemicals in the RoC that did not have animal cancer data. https://doi.org/10.1289/EHP5672.

Estrus synchronization and fixed-time artificial insemination alter calving distribution in Bos indicus influenced beef heifers.

To determine the effects of estrus synchronization (ES) and fixed-time artificial insemination (TAI) on calving distribution in Bos indicus influenced heifers, 751 Bos taurus × Bos indicus beef heifers were enrolled in a completely randomized design at 2 locations from January to May of 2016. Within location, all heifers were randomly assigned to one of two treatments: 1) SYNCH (n = 371); heifers were exposed to the 5-day CO-Synch + CIDR protocol where they were treated with 100 µg of GnRH, 25 mg of PGF2α, and a controlled internal drug releasing insert (CIDR) on d 0; heifers received 50 mg of PGF2α at CIDR removal on d 5, and were treated with 100 µg of GnRH and TAI 66 ± 2 h later on d 8; or 2) CONTROL (n = 380); heifers were exposed to natural service without ES or TAI. On d 9, all heifers were exposed to bulls for the remainder of the breeding season at each location. Blood samples were collected on d -9 and on d 0 to determine pretreatment estrous cyclicity (progesterone ≥ 1.0 ng/mL). Pregnancy was diagnosed via transrectal ultrasonography 54 d after TAI by determining the presence of a viable fetus. Fetal age was estimated based on fetal size and structural features at the time of pregnancy diagnosis. Pregnancy rates on d 54 differed (P < 0.001) between locations, but did not differ (P = 0.777) between CONTROL and SYNCH treatments. Pregnancy rates on d 54 were greater (P < 0.001) in cycling compared with non-cycling heifers (63.9 vs 42.4%). A greater (P < 0.05) proportion of SYNCH heifers became pregnant in the first 19 d of the breeding season compared with CONTROL heifers (52.2 vs 46.4%). Overall breeding season pregnancy rates did not differ (P = 0.982) between treatments. In summary, ES and TAI increased the percentage of heifers that conceived in the first 19 d of the breeding season, and therefore, potentially altered the calving distribution by ensuring that more heifers calve early during the subsequent calving season.

Health consequences of electric lighting practices in the modern world: A report on the National Toxicology Program's workshop on shift work at night, artificial light at night, and circadian disruption.

The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled "Shift Work at Night, Artificial Light at Night, and Circadian Disruption" to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures.

Surveillance for Lyme disease in Canada, 2009 to 2012.

OBJECTIVES: To summarize the first four years of national surveillance for Lyme disease in Canada from 2009 to 2012 and to conduct a preliminary comparison of presenting clinical manifestations in Canada and the United States. METHODS: The numbers and incidence of reported cases by province, month, year, age and sex were calculated. Logistic regression was used to examine trends over time. Acquisition locations were mapped and presenting clinical manifestations reported for jurisdictions where data was available. Variations by province, year, age and sex as well as presenting clinical symptoms were explored by logistic regression. An initial comparative analysis was made of presenting symptoms in Canada and the United States. RESULTS: The numbers of reported cases rose significantly from 144 in 2009 to 338 in 2012 (coefficient = 0.34, standard error = 0.07, P <0.05), mostly due to an increased incidence of infections acquired in Canada. More cases were classified as 'confirmed' (71.5%) than 'probable' (28.5%). Most cases occurred in locations where vector tick populations were known to be present. More men than women were affected (53.4% versus 46.6%), incidence was highest in adults aged 55 to 74 years and in children aged five to 14 years. Most cases (95%) were acquired from April to November. Of cases acquired in endemic areas, 39.7% presented with manifestations of early Lyme disease, while 60.3% had manifestations of disseminated Lyme disease. There were significant differences among age groups, sexes and provinces in the frequencies of reported clinical manifestations. The proportion of cases acquired in endemic areas presenting with early Lyme disease was lower than that reported in the US. CONCLUSION: Lyme disease incidence is increasing in Canada. Most cases are acquired where vector tick populations are spreading and this varies geographically within and among provinces. There is also variation in the frequency of age, season and presenting manifestations. The lower proportion of cases presenting with early Lyme disease in Canada compared with the US suggests lower awareness of early Lyme disease in Canada, but this requires further study.

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity.

Neurons of the lateral olivocochlear (LOC) system project from the auditory brainstem to the cochlea, where they synapse on radial dendrites of auditory nerve fibers. Selective LOC disruption depresses sound-evoked auditory nerve activity in the guinea pig, but enhances it in the mouse. Here, LOC disruption depressed spontaneous auditory nerve activity in the guinea pig. Recordings from single auditory nerve fibers revealed a significantly reduced proportion of fibers with the highest spontaneous firing rates (SRs) and an increased proportion of neurons with lower SRs. Ensemble activity, estimated using round window noise, also decreased after LOC disruption. Decreased spontaneous activity after LOC disruption may be a consequence of reduced tonic release of excitatory transmitters from the LOC terminals in guinea pigs.

Dynorphin release by the lateral olivocochlear efferents may inhibit auditory nerve activity: a cochlear drug delivery study.

Dynorphin (dyn) is suggested to excite the auditory nerve (AN) when released by the lateral olivocochlear (LOC) efferents. However, previous studies evaluated either intravenously delivered dyn-like agents, raising the potential for systemic (central) effects, or agent concentrations unlikely to be achieved via endogenous cochlear release. This study tested the hypothesis that biologically relevant increases in dyn levels in the cochlea achieved via diffusion of the drug of (-)pentazocine across the round window membrane enhances AN firing. In general, amplitude of the cochlear whole-nerve action potential (CAP) was depressed following drug application. These results suggest that dyn released by the LOC neurons would likely act as an inhibitory transmitter substance in the LOC system; neurotransmission is one of the LOC system's vast unknowns.

Disparities in emptying velocity within the left atrial appendage.

AIMS: Pulsed Doppler measurement of left atrial appendage (LAA) emptying velocity, a marker of left atrium contractile function, has been shown to predict success of cardioversion, thrombo-embolic risk, and maintenance of sinus rhythm after cardioversion and pulmonary vein isolation. However, in the published literature, emptying velocity measurement location is not uniform, and no standard currently exists. We assessed the hypothesis that emptying velocity when acquired near the LAA orifice differs from that at the LAA apex. METHODS AND RESULTS: The study group comprised 44 patients (32 in sinus rhythm and 12 in atrial fibrillation) who were able to complete a non-emergent transoesophageal echocardiography. Pulsed Doppler recordings were obtained with the sample volume first positioned 1 cm from the LAA orifice, and then positioned within 1 cm of the LAA apex. At each location, we calculated the average of the peak end-diastolic LAA emptying velocity from five consecutive cardiac cycles. LAA orifice emptying velocity was higher than the apex emptying velocity in all patients. The median velocity at the orifice was 72 cm/s, which was 45% higher than the median velocity at the apex (43 cm/s, P < 0.001). Lower LAA emptying velocity at the orifice was associated with a larger discrepancy between orifice and apex velocities. The ratio of orifice to apex velocity did not vary with orifice velocity. Multivariate analysis demonstrated that clinical patient characteristics were not significant predictors of the discrepancy between orifice and apex velocities. CONCLUSION: LAA emptying velocity is greater at the LAA orifice compared with the LAA apex. Higher, more easily measured velocity and greater variability observed with orifice measurements make it the location of choice for research and clinical applications.

Ventral cochlear nucleus responses to contralateral sound are mediated by commissural and olivocochlear pathways.

In the normal guinea pig, contralateral sound inhibits more than a third of ventral cochlear nucleus (VCN) neurons but excites <4% of these neurons. However, unilateral conductive hearing loss (CHL) and cochlear ablation (CA) result in a major enhancement of contralateral excitation. The response properties of the contralateral excitation produced by CHL and CA are similar, suggesting similar pathways are involved for both types of hearing loss. Here we used the neurotoxin melittin to test the hypothesis that this "compensatory" contralateral excitation is mediated either by direct glutamatergic CN-commissural projections or by cholinergic neurons of the olivocochlear bundle (OCB) that send collaterals to the VCN. Unit responses were recorded from the left VCN of anesthetized, unilaterally deafened guinea pigs (CHL via ossicular disruption, or CA via mechanical destruction). Neural responses were obtained with 16-channel electrodes to enable simultaneous data collection from a large number of single- and multiunits in response to ipsi- and contralateral tone burst and noise stimuli. Lesions of each pathway had differential effects on the contralateral excitation. We conclude that contralateral excitation has a fast and a slow component. The fast excitation is likely mediated by glutamatergic neurons located in medial regions of VCN that send their commissural axons to the other CN via the dorsal/intermediate acoustic striae. The slow component is likely mediated by the OCB collateral projections to the CN. Commissural neurons that leave the CN via the trapezoid body are an additional source of fast, contralateral excitation.

VHL Type 2B gene mutation moderates HIF dosage in vitro and in vivo.

Von Hippel-Lindau (VHL) disease is caused by germline mutations in the VHL tumor suppressor gene, with Type 2B missense VHL mutations predisposing to renal cell carcinoma, hemangioblastoma and pheochromocytoma. Type 2B mutant pVHL is predicted to be defective in hypoxia inducible factor (HIF)-alpha regulation. Murine embryonic stem (ES) cells in which the endogenous wild-type Vhl gene was replaced with the representative Type 2B VHL hotspot mutation R167Q (Vhl(2B/2B)) displayed preserved physiological regulation of both HIF factors with slightly greater normoxic dysregulation of HIF-2alpha. Differentiated Vhl(2B/2B)-derived teratomas overexpressed joint HIF targets Vegf and EglN3 but not the HIF-1alpha-specific target Pfk1. Vhl(2B/2B) teratomas additionally displayed a growth advantage over Vhl(-/-)-derived teratomas, suggestive of a tight connection between perturbations in the degree and ratio of HIF-1alpha and HIF-2alpha stabilization and cell growth. Vhl(2B/2B) mice displayed mid-gestational embryonic lethality, whereas adult Vhl(2B/+) mice exhibited susceptibility to carcinogen-promoted renal neoplasia compared with wild-type littermates at 12 months. Our experiments support a model in which the representative Type 2B R167Q mutant pVhl produces a unique profile of HIF dysregulation, thereby promoting tissue-specific effects on cell growth, development and tumor predisposition.

Deaths from violence in North Carolina, 2004: how deaths differ in females and males.

OBJECTIVE: To identify gender differences in violent deaths in terms of incidence, circumstances, and methods of death. DESIGN: Analysis of surveillance data. SETTING: North Carolina, a state of 8.6 million residents on the eastern seaboard of the US. SUBJECTS: 1674 North Carolina residents who died from violence in the state during 2004. METHODS: Information on violent deaths was collected by the North Carolina Violent Death Reporting System using data from death certificates, medical examiner reports, and law enforcement agency incidence reports. RESULTS: Suicide and homicide rates were lower for females than males. For suicides, females were more likely than males to have a diagnosis of depression (55% v 36%), a current mental health problem (66% v 42%), or a history of suicide attempts (25% v 13%). Firearms were the sole method of suicide in 65% of males and 42% of females. Poisonings were more common in female than male suicides (37% v 12%). Male and female homicide victims were most likely to die from a handgun or a sharp instrument. Fifty seven percent of female homicides involved intimate partner violence, compared with 13% of male homicides. Among female homicides involving intimate partner violence, 78% occurred in the woman's home. White females had a higher rate of suicide than African-American females, but African-American females had a higher rate of homicide than white females. CONCLUSIONS: The incidence, circumstances, and methods of fatal violence differ greatly between females and males. These differences should be taken into account in the development of violence prevention efforts.

Test characteristics from latent-class models of the California Mastitis Test.

We evaluated (using latent-class models) the ability of the California Mastitis Test (CMT) to identify cows with intramammary infections on the day of dry-off. The positive and negative predictive values of this test to identify cows requiring dry-cow antibiotics (i.e. infected) was also assessed. We used 752 Holstein-Friesian cows from 11 herds for this investigation. Milk samples were collected for bacteriology, and the CMT was performed cow-side, prior to milking on the day of dry-off. At the cow-level, the sensitivity and specificity of the CMT (using the four quarter results interpreted in parallel) for identifying all pathogens were estimated at 70 and 48%, respectively. If only major pathogens were considered the sensitivity of the CMT increased to 86%. The negative predictive value of the CMT was >95% for herds with major-pathogen intramammary-infection prevalence <15%, so that selective dry-cow therapy might be reasonable for such herds if cows were screened with the CMT.

Asphyxia and depolarization increase adenosine levels in perilymph.

Extracellular adenosine has been suggested as a modulator of cochlear function. To date the release of adenosine into the extracellular spaces of the cochlea has not been demonstrated. Therefore, experiments were designed to examine whether adenosine release into perilymph could be detected in response to depolarization by high potassium concentrations or in response to asphyxia. For this purpose, the perilymph compartment of guinea pigs was perfused with an artificial perilymph and the effluent assayed for ATP, ADP, AMP and adenosine. Results indicate that potassium induced a slight, significant increase and asphyxia induced a very large, significant increase in adenosine levels in perilymph effluent. No changes in the levels of the other compounds were measured. It is concluded that depolarization and asphyxia can induce the release of adenosine into perilymph.