Forgetting to Take Medication, Treatment Adherence and Their Relationship with Viral Load Suppression Among People Living with HIV in the Kilimanjaro Region, Tanzania.

Background: Antiretroviral therapy (ART) adherence is crucial for virological suppression and positive treatment outcomes among people living with HIV (PLHIV), but remains a challenge in ensuring patients achieve and sustain viral load suppression. Despite the recommended use of digital tools medications uptake reminders, the contribution of forgetting to take medication is unknown. This study investigated the contribution of forgetting to take medication on the total missed medication and its effects on detectable viral load (VL). Methods: This mixed-method research was conducted among children, adolescents, pregnant, and breastfeeding women living with HIV on ART in northern Tanzania. Forgetting to take medication constituted reporting to have missed medication due to forgetfulness. A multivariable logistic regression model was used to estimate the adjusted odds ratio (AOR) with a 95% confidence interval (CI) to determine the contribution of forgetting medication intakes on total missed medication and other factors associated with having a detectable VL. Results: Of 427 respondents, 33.3% were children, 33.4% adolescents, and 33.3% pregnant and breastfeeding women, whose median age (interquartile range) was 9 (7-12), 18 (16-18), and 31 (27-36) years, respectively. Ninety-two (22.3%) reported missing medication over the past month, of which 72 (17.9%) was due to forgetting. Forgetting to take medication (AOR: 1.75 95% CI: 1.01-3.06) and being on second-line regimen (AOR: 2.89 95% CI: 1.50-5.55) increased the chances of a detectable VL, while females had lower chances of detectable VL (AOR: 0.62 95% CI: 0.41-0.98). The themes on the reasons for forgetting to take medication from qualitative results included being busy with work and the importance of reminders. Conclusion: Forgetting to take medication is common among PLHIV and an important predictor of a detectable VL. This calls for the use of automated short message services (SMS) reminders or Digital Adherence Tools with reminders to improve and promote good ART adherence among PLHIV.

NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease.

BACKGROUND: Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). METHODS: NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning. RESULTS: Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*102 pg/mL vs. 3.9*102 pg/mL, p < 0.01, respectively). Serum NfL levels were higher in symptomatic RVCL-S than pre-symptomatic carriers (33.5 pg/mL vs. 5.9 pg/mL, p = 0.02). Pre-symptomatic RVCL-S carriers had increased CSF NfL levels compared to controls < 45 years (5.2*102 pg/mL vs. 1.9*102 pg/mL, p < 0.01). No differences were found in GFAP levels across groups, but in RVCL-S carriers higher serum levels of both NfL and GFAP were linked to poorer global cognitive functioning (ß[95%CI] = - 2.86 [- 5.58 to - 0.13], p = 0.04 and ß[95%CI] = - 6.85 [- 11.54 to - 2.15], p = 0.01, respectively) and prolonged psychomotor test times (ß[95%CI] = 6.71 [0.78-12.65], p = 0.03 and ß[95%CI] = 13.84 [3.09-24.60], p = 0.01). DISCUSSION: Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls.

Characterising sustainability certification standards in dairy production.

Despite the increasing use of private certification standards to meet the demand for sustainable dairy production, research into these standards is lacking. In this paper, we characterised sustainability certification standards currently used in dairy production. A literature search for dairy sustainability initiatives revealed one hundred-and-sixteen possible standards. In total, 19 of these were determined to qualify as 'sustainability certification standards' based on our selection criteria and were available in English or Dutch language. The standards were analysed using publicly available documents of the most recent version. The analysis included three key components: (i) general characteristics of the standard (such as the geographic origin, year founded, most recent updates), (ii) a thematic coverage analysis of the sustainability themes covered in each standard and (iii) evaluation of the inherent trade-offs within each standard utilising the opposing aspects of credibility, accessibility, and continuous improvement (the 'devil's triangle'). The comparison of general characteristics of the 19 standards revealed a wide variation in the characteristics of standards such as organisation type (i.e. nongovernmental organisations, individual dairy processor or other dairy sector actors), the number of indicators included, but also in the sustainability themes they cover, and how they balance the credibility, accessibility, and continuous improvement. The environmental pillar is most frequently and comprehensively addressed, whereas the economic pillar is least frequently and least comprehensively addressed. The 'devil's triangle' trade-off analysis revealed that credibility and accessibility, from the standard's perspective, are often transparently described and assured within the documents of standards. In contrast, continuous improvement is infrequently focused upon by standards. Overall, the variability in standards may allow farmers to choose a standard that aligns with his/her conviction or stage of development but might also create consumer or farmer mistrust in standards.

"The phone number tells us good things we didn't know before." Use of interactive voice response calling for improving knowledge and uptake of family planning methods among Maasai in Tanzania.

Maasai living in the Arusha region, Tanzania, face challenges in feeding their children because of decreasing grazing grounds for their cattle. Therefore, they requested birth control methods. Previous studies have shown that lack of knowledge about, and poor access to, family planning (FP) may worsen the situation. We developed an interactive voice response calling (IVRC) platform for Maasai and health care workers (HCW) to create a venue for communication about FP to increase knowledge and access to FP. The objective of this study was to explore the effect of the platform on knowledge, access and use of family planning methods. We applied a participatory action research approach using mixed methods for data collection to develop and pilot-test an mHealth-platform with IVRC using Maa language. We enrolled Maasai-couples and HCW in Monduli District (Esilalei ward), Arusha Region, and followed them for 20 months. A baseline assessment was done to explore knowledge about FP. Furthermore, we abstracted information on FP clinic visits. Based on that, we developed a system called Embiotishu. A toll-free number was provided to interact with the system by calling with their phone. The system offers pre-recorded voice messages with information about FP and reproductive health to educate Maasai. The system recorded the number of calls and the type of information accessed. We measured the outcome by (1) a survey investigating the knowledge of contraceptive methods before and after Embiotishu and (2) counting the number of clinic visits (2018-2020) from medical records and feedback from qualitative data for FP used among Maasai. The acceptability and feasibility were explored through focus group discussions (FGDs) with Maasai and in-depth interviews (IDIs) with HCW. We recruited 76 Maasai couples whom we interviewed during the baseline assessment. The overall knowledge of contraceptives increased significantly (p<0.005) in both men and women. The number of clinic visits rose from 137 in 2018 to 344 in 2019 and 228 in the first six months of 2020. Implants were the most prescribed family planning method, followed by injections and pills, as found in medical records. The number of incoming calls, missed calls, and questions were 24,033 over 20 months. Out of these calls, 14,547 topics were selected. The most selected topics were modern contraceptives (mainly implants, condoms, tubal ligation, and vasectomy). Natural methods of contraception (vaginal fluid observations, calendar, and temperature). Our study has shown that the IVRC system led to an improvement in knowledge about and access to contraceptives. Furthermore, it has potential to increase access to health information as well as improve dialogue between Health workers and Maasai.

Effect of a customized digital adherence tool on retention in care and adherence to antiretroviral treatment in breastfeeding women, children and adolescents living with HIV in Tanzania: a mixed-methods study followed by clinical trials.

BACKGROUND: Adherence to antiretroviral (ARV) treatment for HIV infection is challenging because of many factors. The World Health Organization (WHO) has recommended using digital adherence technologies (DATs). However, there is limited evidence on how DATs improve adherence. Wisepill® is an internet-enabled medication dispenser found feasible and acceptable in several studies. However, limited evidence is available on its effectiveness in improving ART adherence, specifically among children and adolescents. Furthermore, DATs are often developed without involving the target groups. We propose a two-stage project consisting of a formative study to customize an existing Wisepill DAT intervention and a randomized clinical trial to investigate the effectiveness of DAT combined with reminder cues and tailored feedback on adherence to ARV treatment among children and adolescents living with HIV and retention in care among breastfeeding women living with HIV in Kilimanjaro and Arusha Region, Tanzania. METHODS: We will conduct a formative mixed-methods study and three sub-trials in Kilimanjaro and Arusha Regions among (1) children aged 0-14 years and their caregivers, (2) adolescents aged 15-19 years and (3) breastfeeding women and their HIV-negative infants. In the formative study, we will collect and analyse data on needs and contents for DATs, including the contents of short message service (SMS) texts and tailored feedback. The results will inform the customization of the DAT to be tested in the sub-trials. In the trials, participants will be randomized in the intervention arm, where the DAT will be implemented or the control arm, where standard care will be followed. Participants in the intervention arm will take their medication from the Wisepill box and receive daily reminder texts and tailored feedback during clinic visits. DISCUSSION: If the intervention improves adherence to ART and the devices are acceptable, accurate and sustainable, the intervention can be scaled up within the National Aids Control Programmes. TRIAL REGISTRATION: PACTR202301844164954, date 27 January 2023.

Modeling the economic impacts of mobility scores in dairy cows under Irish spring pasture-based management.

Moderate to severe forms of suboptimal mobility on dairy cows are associated with yield losses, whereas mild forms of suboptimal mobility are associated with elevated somatic cell count and an increased risk to be culled. Although the economic consequences of severe forms of suboptimal mobility (also referred as clinical lameness) have been studied extensively, the mild forms are generally ignored. Therefore, the aim of the current study was to determine the economic consequences associated with varying prevalence and forms of suboptimal mobility within spring calving, pasture-based dairy herds. A new submodel predicting mobility scores was developed and integrated within an existing pastured-based herd dynamic model. Using a daily timestep, this model simulates claw disorders, and the consequent mobility score of individual cows. The impact of a cow having varying forms of suboptimal mobility on production and reproduction was simulated. The economic impact was simulated including treatment costs, as well as the production and reproductive impacts of varying levels of suboptimal mobility. Furthermore, different genetic predispositions for mobility issues and their interaction with herd-level management associated with each level of suboptimal mobility were simulated. Overall, 13 scenarios were simulated, representing a typical spring calving, pasture-based dairy herd with 100 cows. The first scenario represents a perfect herd wherein 100% of the cows had mobility score 0 (optimal mobility) throughout the lactation. The remaining 12 scenarios represent a combination of (1) 3 different herd-management levels, and (2) 4 different levels of a genetic predisposition for suboptimal mobility. The analysis showed that a 17% decrease in farm net profit was achieved in the worst outcome (wherein just 5% of the herd had optimal mobility) compared with the perfect herd. This was due to reduced milk yield, increased culling, and increased treatment costs for mobility issues compared the ideal scenario.

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S): An update on basic science and clinical perspectives.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, underrecognized, systemic small vessel disease caused by heterozygous C-terminal truncating TREX1 mutations. The disease is characterized by vascular retinopathy, focal neurological complaints, cognitive decline and a wide range of systemic manifestations, including Raynaud's phenomenon, anemia and liver and kidney disease. Eventually, RVCL-S leads to premature death. The underlying pathological finding in RVCL-S is a nonatherosclerotic, amyloid-negative angiopathy involving small arteries and capillaries. However, the exact mechanisms by which the truncated TREX1 protein causes angiopathy remains unknown. Timely recognition of this disease is important to slow down and treat complications of the disorder, but also to prevent unnecessary (invasive) diagnostic or therapeutic procedures. As we move forward, translational research combining basic science advances and clinical findings as well as studies focusing on natural history following RVCL-S patients at different disease stages, will be critical to help elucidate RVCL-S pathophysiology. These studies will also provide the tools to identify appropriate biomarkers and therapeutic agent options for RVCL-S patients.

Predicting viral load suppression by self-reported adherence, pharmacy refill counts and real time medication monitoring among people living with HIV in Tanzania.

INTRODUCTION: Monitoring of adherence to antiretroviral treatment (ART) is of utmost importance to prevent treatment failure. Several measures to monitor adherence have been applied in low-resource settings and they all have pros and cons. Our objective was to examine whether any of the following adherence measures is a better predictor of participants' viral load suppression: (1) self-report, (2) pharmacy refill count, (3) Real Time Medication Monitoring (RTMM), (4) a combination of self-report and pharmacy refill count or (5) all three adherence assessment methods combined. METHODOLOGY: This was a post-hoc analysis of data from our 48-week REMIND-HIV randomized controlled trial in which adherence to ART was measured using self-report, pharmacy refill counts and RTMM among ART-experienced adults living with HIV subjectively judged to be nonadherent to ART. For each adherence measure, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting virological failure defined as a viral load (VL) of > 20 copies/mL. To determine at which percentage of adherence the prediction was strongest, we evaluated adherence cut-offs of 80%, 85%, 90%, 95% and 100% using receiver operating characteristic (ROC) curves. VL data were obtained after 48 weeks of follow-up in the trial. RESULTS: A total of 233 people living with HIV (PLHIV) were included in this analysis. When comparing the ability of self-reported adherence with pharmacy refill count and RTMM adherence to predict viral load > 20 copies/ml, self-reported adherence had the lowest sensitivity, ranging from 6 to 17%, but the highest specificity, ranging from 100 to 86%, depending on cut-off values from 80 to 100%. Area under the ROC curves (AUC) were 0.54 for RTMM, 0.56 for pharmacy refill count and 0.52 for self-report, indicating low discriminatory capacity for each of the adherence measures. When we combined the self-report and pharmacy refill count measures, sensitivity increased, ranging from 28 to 57% but specificity decreased, ranging from 83 to 53%. When all three measures were combined, we observed the highest value of sensitivity, ranging from 46 to 92%, and PPV, ranging from 32 to 36%, at high cut-offs ranging from 80 to 100%. Upon combination of three adherence measures, the AUC increased to 0.59. CONCLUSION: Our results show that adherence assessed exclusively by self-report, pharmacy refill count or RTMM were insufficiently sensitive to predict virologic failure. Sensitivity markedly improved by combining all three measures, but the practical feasibility of such an approach would need to be studied.

Effect of feeding single-dam or pooled colostrum on maternally derived immunity in dairy calves.

The role of colostrum management in providing adequate immunological protection to neonatal calves has been widely investigated, and thresholds for colostrum quality, as well as optimum volume and timing for colostrum feeding have been established. However, limited information is available on the effect of colostrum source (single dam or pooled) on passive immunity, as well as subsequent antibody survival in the calf. This study aimed to assess the effect of feeding single-dam colostrum (own and other dam) or pooled colostrum on transfer of passive immunity, and also investigate the rate of depletion of disease-specific antibodies among dairy calves. In total, 320 cows and 119 dairy heifer calves were enrolled in the study. Calves were blood-sampled immediately after birth and received either own-dam, other-dam, or pooled colostrum. Calves were blood-sampled at 24 h to assess serum IgG concentrations and at monthly intervals thereafter to document disease-specific antibody survival. Mean colostrum IgG concentration was higher for other-dam treatment group, whereas own-dam and pooled treatments were similar. For all treatment groups, the mean IgG concentration was >80 mg/mL, exceeding the quality threshold of 50 mg/mL. Mean calf serum IgG concentration was lower for calves fed pooled colostrum compared with those that received colostrum from a single cow. There was a negative association with 24-h serum IgG and calf birth bodyweight; calves <30 kg at birth had the highest 24-h serum IgG concentration. Survival of antibodies to bovine viral diarrhea, Salmonella infection, leptospirosis, bovine parainfluenza 3 virus, bovine respiratory syncytical virus, rotavirus, and coronavirus was not associated with colostrum source; however, antibodies to infectious bovine rhinotracheitis had a greater period of survival among calves fed own-dam colostrum. We found that feeding single-dam colostrum can thus improve calf immunity through increased serum IgG levels and antibody survival rates. Furthermore, we hypothesize that immune exclusion may occur with pooled colostrum; therefore, providing pooled colostrum may still be a good practice as long as it can be ensured that enough antibodies are absorbed into the blood stream to deal with pathogens calves may encounter because different dams may have antibodies against different strains of viruses and bacteria, yielding cross protection.

Identifying women with fear of childbirth with the Dutch Fear of Birth Scale and its added value for consultations.

OBJECTIVES: Determine whether the Fear of Birth Scale (FOBS) is a useful screening instrument for Fear of Childbirth (FoC) and examine the potential added value of screening by analyzing how often pregnant women discuss their FoC during consultation. METHODS: This cross-sectional survey study included nulliparous pregnant women of all gestational ages, recruited via the internet, hospital and midwifery practices. The online questionnaires included the FOBS and Wijma Delivery Expectations Questionnaire version A (W-DEQ A). The latter was used as golden standard for assessing FoC (cutoff: ≥85). RESULTS: Of the 364 included women, 67 (18.4%) had FoC according to the W-DEQ A. Using the FOBS with a cutoff score of ≥49, the sensitivity was 82.1% and the specificity 81.1%, with 111 (30.5%) women identified as having FoC. Positive predictive value was 49.5% and negative predictive value 95.3%. Of the women with FoC (FOBS ≥49), 68 (61.3%) did not discuss FoC with their caregiver. CONCLUSION: The FOBS is a useful screening instrument for FoC. A positive score must be followed by further assessment, either by discussing it during consultation or additional evaluation with the W-DEQ A. The majority of pregnant women with FoC do not discuss their fears, underscoring the need for screening.

Consumer strategies towards a more sustainable food system: insights from Switzerland.

BACKGROUND: To improve the sustainability performance of food systems, both consumption- and production-side changes are needed. OBJECTIVES: To this end, we assessed multiple sustainability impacts of 6 consumer strategies together with production-side aspects such as organic and circularity principles for Switzerland. METHODS: Two strategies encompassed dietary changes: following a pescetarian diet and adhering to the national dietary guidelines. Two strategies employed alternative farming systems: increasing the share of organic production and, in addition, applying the circularity principle of avoiding feed-food competition by limiting livestock feed to low-opportunity-cost biomass. A fifth strategy reduced food waste. The sixth strategy increased the share of domestic produce. For all strategies, we assessed greenhouse gas emissions, land use, nitrogen surplus, social risks, diet quality, and diet costs. RESULTS: The strategies revealed trade-offs between impact categories, unless combined in a synergistic way. Whereas dietary changes towards more plant-based diets reduced environmental impacts (≤51%) and increased diet quality (≤57%), they increased social risks due to increased sourcing from contexts with potentially bad labor conditions (≤19%). Further, when the share of organic produce was increased, land use and dietary costs were increased (≤33% and ≤42%, respectively). The effect on land use could, however, be reversed when circularity principles were introduced in addition to the organic production standard, resulting in reductions for all environmental indicators (≤75%). Reducing food waste and increasing the share of domestic produce led to better sustainability performance as well, but at lower orders of magnitude. CONCLUSIONS: Combining all proposed strategies could lead to substantial favorable changes on all impact categories assessed, but would require a thorough transformation of the current food system. However, the sum of individual consumers each following only 1 of the strategies proposed would make an important contribution towards improving the sustainability performance of the Swiss food system.

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is caused by TREX1 mutations. High-quality systematic follow-up neuroimaging findings have not been described in presymptomatic and symptomatic mutation carriers. We present MR imaging findings of 29 TREX1 mutation carriers (20-65 years of age) and follow-up of 17 mutation carriers (30-65 years of age). Mutation carriers younger than 40 years of age showed a notable number of punctate white matter lesions, but scan findings were generally unremarkable. From 40 years of age onward, supratentorial lesions developed with long-term contrast enhancement (median, 24 months) and diffusion restriction (median, 8 months). In these lesions, central susceptibility artifacts developed, at least partly corresponding to calcifications on available CT scans. Some lesions (n = 2) additionally showed surrounding edema and mass effect (pseudotumors). Cerebellar punctate enhancing lesions developed mainly in individuals older than 50 years of age. These typical neuroimaging findings should aid neuroradiologic recognition of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, which may enable early treatment of manifestations of the disease.

Effect of Digital Adherence Tools on Adherence to Antiretroviral Treatment Among Adults Living With HIV in Kilimanjaro, Tanzania: A Randomized Controlled Trial.

BACKGROUND: Lifelong adherence to antiretroviral treatment remains challenging for people living with HIV (PLHIV). The aim of this study was to investigate whether any of 2 digital adherence tools could improve adherence among PLHIV in Kilimanjaro, Tanzania. METHODS: We performed a parallel 3-arm, nonblinded, randomized controlled trial with 1:1:1 allocation. We included adults aged between 18 and 65 years, living in Kilimanjaro region, and who were on antiretroviral treatment for at least 6 months. Their adherence, as judged by the study nurses, had to be suboptimal. In one arm, participants received reminder short message service (SMS) texts, followed by a question SMS. In the second arm, participants received a real-time medication monitoring (RTMM) device (Wisepill) with SMS reminders. In the third arm, participants received standard care only. The primary outcome of mean adherence over 48 weeks was compared between arms using between-group t tests in a modified intention-to-treat analysis. RESULTS: In each arm, we randomized 83 participants: data of 82 participants in the RTMM arm, 80 in the SMS arm, and 81 in the standard care arm were analyzed. The average (over 48 weeks) adherence in the SMS, RTMM, and control arms was 89.6%, 90.6%, and 87.9% for pharmacy refill; 95.9%, 95.0%, and 95.2% for self-report in the past week; and 97.5%, 96.6%, and 96.9% for self-report in the past month, respectively (P values not statistically significant). CONCLUSIONS: Receiving reminder SMS or RTMM combined with feedback about adherence levels and discussion of strategies to overcome barriers to adherence did not improve adherence to treatment and treatment outcome in PLHIV. CLINICAL TRIAL NUMBER: PACTR201712002844286.

The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I.

To prevent accumulation of misfolded proteins in the endoplasmic reticulum, chaperones perform quality control on newly translated proteins and redirect misfolded proteins to the cytosol for degradation by the ubiquitin-proteasome system. This pathway is called ER-associated protein degradation (ERAD). The human cytomegalovirus protein US2 induces accelerated ERAD of HLA class I molecules to prevent immune recognition of infected cells by CD8+ T cells. Using US2-mediated HLA-I degradation as a model for ERAD, we performed a genome-wide CRISPR/Cas9 library screen to identify novel cellular factors associated with ERAD. Besides the identification of known players such as TRC8, p97, and UBE2G2, the ubiquitin-fold modifier1 (UFM1) pathway was found to affect degradation of HLA-I. UFMylation is a post-translational modification resembling ubiquitination. Whereas we observe ubiquitination of HLA-I, no UFMylation was detected on HLA-I or several other proteins involved in degradation of HLA-I, suggesting that the UFM1 pathway impacts ERAD in a different manner than ubiquitin. Interference with the UFM1 pathway seems to specifically inhibit the ER-to-cytosol dislocation of HLA-I. In the absence of detectable UFMylation of HLA-I, UFM1 may contribute to US2-mediated HLA-I degradation by misdirecting protein sorting indirectly. Mass spectrometry analysis of US2-expressing cells showed that ribosomal proteins are a major class of proteins undergoing extensive UFMylation; the role of these changes in protein degradation may be indirect and remains to be established.

Returning of antiretroviral medication dispensed over a period of 8 months suggests non-adherence despite full adherence according to real time medication monitoring.

Real-time medication monitoring (RTMM) may potentially enhance adherence to antiretroviral treatment (ART). We describe a participant in an ongoing trial who, shortly after completing trial participation, died of cryptococcal meningitis despite high levels of adherence according to self-report, pill-counts and RTMM (> 99%). However, she evidenced consistently high HIV viral load throughout the 48-week study follow-up. Subsequently, her relatives unsolicitedly returned eight months' dispensed ART medication that she was supposed to have taken. This brief report illustrates the challenges of adherence measurements including RTMM, and reinforces the need to combine adherence assessments with viral load monitoring in HIV care.

Optical coherence tomography detects retinal changes in hereditary cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers. METHODS: Twenty-one D-CAA mutation carriers (n = 8 presymptomatic, n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of ≥1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age. RESULTS: The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) µm vs. 99 (87-108) µm; P = 0.006]. Both presymptomatic [111 (93-122) µm vs. 131 (123-143) µm; P < 0.001] and symptomatic carriers [119 (95-128) µm vs. 131 (123-143) µm; P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls. CONCLUSIONS: Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression.

Associating mobility scores with production and reproductive performance in pasture-based dairy cows.

Lameness in dairy cows can have significant effects on cow welfare, farm profitability, and the environment. To determine the economic and environmental consequences of lameness, we first need to quantify its effect on performance. The objective of this study, therefore, was to determine the associations of various production and reproductive performance measurements (including milk, fat, and protein yield, somatic cell count, calving interval, cow death, or cow slaughter), and mobility scores in spring-calving, pasture-based dairy cows. We collected mobility scores (0 = good, 1 = imperfect, 2 = impaired, and 3 = severely impaired mobility), body condition scores, and production data for 11,116 cows from 68 pasture-based dairy herds. Linear mixed modeling was used to determine the associations between specific mobility scores and milk, fat and protein yield, and somatic cell count and calving interval. Binomial logistic regression was used to determine the association between mobility score and cow death, or slaughter. Significant yield losses of up to 1.4% of the average yield were associated with mobility score 2 and yield losses of up to 4.7% were associated with mobility score 3 during the early scoring period. Elevated somatic cell count was associated with all levels of suboptimal mobility during the late scoring period. Cows with a mobility score of 2 during the early scoring period were associated with longer calving interval length, whereas only cows with a mobility score of 3 during the late scoring period were associated with longer calving interval length. Cows with a mobility score ≥1 were more likely to be culled during both scoring periods. Our study, therefore, shows an association between specific mobility scores and production and reproductive performance in spring-calving, pasture-based dairy cows scored during the summer grazing period.

Cow and herd-level risk factors associated with mobility scores in pasture-based dairy cows.

Lameness in dairy cows is an area of concern from an economic, environmental and animal welfare point of view. While the potential risk factors associated with suboptimal mobility in non-pasture-based systems are evident throughout the literature, the same information is less abundant for pasture-based systems specifically those coupled with seasonal calving, like those in Ireland. Therefore, the objective of this study was to determine the potential risk factors associated with specific mobility scores (0 = good, 1 = imperfect, 2 = impaired, and 3 = severely impaired mobility) for pasture-based dairy cows. Various cow and herd-level potential risk factors from Irish pasture-based systems were collected and analyzed for their association with suboptimal mobility, whereby a mobility score of 0 refers to cows with optimal mobility and a mobility score ≥ 1 refers to a cow with some form of suboptimal mobility. Combined cow and herd-level statistical models were used to determine the increased or decreased risk for mobility score 1, 2, and 3 (any form of suboptimal mobility) compared to the risk for mobility score 0 (optimal mobility), as the outcome variable and the various potential risk factors at both the cow and herd-level were included as predictor type variables. Cow-level variables included body condition score, milk yield, genetic predicted transmitting ability for 'lameness', somatic cell score, calving month and cow breed. Herd-level variables included various environmental and management practices on farm. These analyses have identified several cow-level potential risk factors (including low body condition score, high milk yield, elevated somatic cell count, stage of lactation, calving month, and certain breed types), as well as various herd-level potential risk factors (including the amount of time taken to complete the milking process, claw trimmer training, farm layout factors and foot bathing practices) which are associated with suboptimal mobility. The results of this study should be considered by farm advisors when advising and implementing a cow/herd health program for dairy cows in pasture-based systems.

Pre-weaning management of calves on commercial dairy farms and its influence on calf welfare and mortality.

Welfare and management of calves is of increasing interest and also influences performance of these animals in later life. The aim of this study was to assess management and environmental conditions under which pre-weaned dairy calves are reared on commercial Irish dairy farms. We included 47 spring-calving, pasture-based herds in this study. Herd and animal-specific data, such as mortality rate, age and breed, were gathered from all participants via the HerdPlus® database. Information pertaining to management practices was collected by conducting an interview with the principal calf rearer, while an assessment of calf housing facilities was conducted to identify conditions calves were reared in. The environmental assessment included measurements of space allowance per calf, as well as feeding equipment hygiene. To assess calf behaviour video observations were used, while accounting for the number of calves present in a group and the space available per calf. Faecal samples were also collected to determine the presence of enteric pathogens among calves. To compare calf space allowance, group size and presence of enteric pathogens early and late in the calving season each farm was visited twice. Calf mortality was not associated with either herd size, space allowance per calf or post-colostrum feeding practices. Higher calf mortality was identified among herds which reported experiencing an on-set of calf pneumonia during weeks 8 to 10 of the calving season. This study demonstrates that factors associated with calf welfare on commercial Irish dairy farms (e.g. space allowance, mortality rate) are independent of herd size. Some management practices however, such as methods used for treating health issues can affect rates of calf mortality experienced. Calf mortality, for example, was lower in herds which treated diarrhoea cases by administering electrolytes, while continuing to offer milk. Behavioural observations indicate that smaller group sizes could promote expression of positive behaviours, potentially resulting from an overall improvement in welfare. Space allowance per calf was not associated with observed behaviour frequencies. We also identified that similar rates of calf mortality are experienced across herds of different sizes.

Evaluating the effects of storage conditions on dry matter loss and nutritional quality of grain legume fodders in West Africa.

Feed scarcity is a major challenge for livestock production in West Africa, especially during the dry season when grass quality and quantity on grazing lands are inadequate. In the dry season, crop residues are a key source of livestock feed. The residues of grain legumes, also known as grain legume fodders (GLFs), are stored and traded for feeding in the dry season. The objectives of our experiment were to evaluate the effects of storage conditions and duration on dry matter (DM) and nutritional quality of GLFs, and to assess the risk of aflatoxin in stored groundnut fodder. The experiment was designed as a factorial trial with 18 treatment combinations with four replicates (4 farms). The treatments included: 3 types of GLFs (cowpea, groundnut and soybean fodder), 3 types of storage locations (rooftop, room and tree-fork) and 2 types of packaging (packed in polythene sacks and unpacked but tied with rope). Over a 120 day storage period, DM quantity reduced by an average of 24 % across all storage conditions, showing a range from 14 % in the best condition (sacks and rooms) to 35 % in the worst condition (bundles tied with rope and stored on rooftops or tree-forks). Soybean fodder had no leaves, the lowest crude protein content (CP) and organic matter digestibility (OMD), and the highest content of cell wall components compared to cowpea and groundnut fodder. These nutritional quality parameters in soybean fodder hardly changed during storage. Cowpea and groundnut fodder showed a decrease in leaf-to-stem ratio (LSR), CP and OMD, and an increase in the content of cell wall components during storage, but their nutritional value remained better than that of soybean fodder. Storage in sacks resulted in less DM loss, in less reduction of LSR and in a smaller increase of the content of cell wall components than storage of bundles tied with rope. Our study shows that the DM loss, the decrease in LSR, and the increase in the content of cell wall components can be prevented partly by storing GLFs in sacks instead of tying bundles with rope, and to a minor extent by storing in rooms instead of in the open air. Aflatoxin was not detectable in the groundnut fodder samples. Our results highlight that attention to storage conditions can improve the feeding value of GLFs which are key for livestock nutrition during the dry season.