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Introduction: MTSS1 is an I-BAR protein that interacts with the actin cytoskeleton and the cell membrane and is speculated to play a role in cell motility, tumor metastasis, and cardiogenesis. Enhancer variants that reduce the expression of MTSS1 in the human left ventricle have been associated with cardioprotective traits in genome-wide association studies. However, the effect of MTSS1 downregulation on the development of heart disease has not been studied in experimental models. Here we tested the hypothesis that reduction of MTSS1 protects against dilated cardiomyopathy (DCM) in vitro and in vivo . Methods: We used CRISPR-Cas9 to knock out MTSS1 in induced pluripotent stem cells (iPSCs) harboring pathogenic variants from patients with severe DCM. DCM iPSC lines with and without MTSS1 were then differentiated into cardiomyocytes and phenotyped in vitro . A DCM mouse model containing a TPM1 D230N transgene was crossed with a mouse model heterozygous for Mtss1 knockout. Progeny from this F1 cross were assessed for differences in cardiac structure and function via echocardiography. Results: MTSS1 deletion restored the beta-adrenergic response in DCM iPSC cardiomyocytes. In parallel, Mtss1 deletion partially rescued DCM-associated phenotypes including left ventricular dilation and reduced ejection fraction in mice. Conclusions: Our initial results suggest a causal link between MTSS1 reduction and cardioprotection in DCM. Inhibiting cardiac MTSS1 may hold therapeutic potential for DCM, though the cellular mechanisms through which MTSS1 affects cardiac phenotypes remain under investigation.

Heart failure (HF) is a leading cause of cardiovascular morbidity and mortality, yet the contribution of common genetic variation to HF risk has not been fully elucidated, particularly in comparison to other common cardiometabolic traits. We conducted a multi-ancestry genome-wide association study (GWAS) meta-analysis of all-cause HF including up to 56,722 HF cases and 1,133,054 controls, identifying 4 novel loci. We then performed a multi-ancestry multivariate association study of HF and related cardiac imaging endophenotypes, identifying 71 conditionally-independent variants, including 16 novel loci. Secondary colocalization and transcriptome-wide association analyses identified known and novel candidate cardiomyopathy genes, which were validated in gene-expression profiling of failing and healthy human hearts. Colocalization, gene expression profiling, and Mendelian randomization provided convergent evidence for the roles ofBCKDHAand circulating branch-chain amino acids in heart failure and cardiac structure. Finally, proteome-wide Mendelian randomization revealed 11 circulating proteins associated with HF or quantitative imaging traits. These analyses highlight similarities and differences among heart failure and associated cardiovascular imaging endophenotypes, implicate novel common genetic variation in the pathogenesis of HF, and identify circulating proteins that may represent novel cardiomyopathy treatment targets.

Factors that influence viral response when antiretroviral therapy (ART) is initiated in neonates are not well characterized. We assessed if there is consistency in predictive factors when operationalizing viral response using different methods. Data were collected from a clinical study in South Africa that started ART in neonates within 14 days of birth (2013–2018). Among 61 infants followed for ≥48 weeks after ART initiation, viral response through 72 weeks was defined by three methods: (1) clinical endpoints (virologic success, rebound, and failure), (2) time to viral suppression, i.e., any viral load (VL: copies/mL) &lt, 400, &lt, 50, or target not detected (TND) using time-to-event methods, and (3) latent class growth analysis (LCGA) to empirically estimate discrete groups with shared patterns of VL trajectories over time. We investigated the following factors: age at ART initiation, sex, birthweight, preterm birth, mode of delivery, breastfeeding, pre-treatment VL and CD4, maternal ART during pregnancy, and maternal VL and CD4 count. ART was initiated 0–48 h of birth among 57.4% of the infants, 48 h–7 days in 29.5% and 8–14 days in 13.1%. By Method 1, infants were categorized into ‘success’ (54.1%), ‘rebound’ (21.3%), and ‘failure’ (24.6%) for viral response. For Method 2, median time to achieving a VL &lt, 50, or TND was 58, 123, and 331 days, respectively. For Method 3, infants were categorized into three trajectories: ‘rapid decline’ (29.5%), ‘slow decline’ (47.5%), and ‘persistently high’ (23.0%). All methods found that higher pre-treatment VL, particularly &gt, 100,000, was associated with less favorable viral outcomes. No exposure to maternal ART was associated with a better viral response, while a higher maternal VL was associated with less favorable viral response and higher maternal CD4 was associated with better viral response across all three methods. The LCGA method found that infants who initiated ART 8–14 days had less favorable viral response than those who initiated ART earlier. The other two methods trended in a similar direction. Across three methods to operationalize viral response in the context of early infant treatment, findings of factors associated with viral response were largely consistent, including infant pre-treatment VL, maternal VL, and maternal CD4 count.

BACKGROUND: Prompt initiation of antiretroviral therapy (ART) for HIV-infected infants is strongly recommended but diagnostic confirmation is important as committing children to life-long ART carries serious health and social implications. METHODS: Two HIV-exposed infants in Johannesburg, South Africa were identified presenting with unusual trajectories of diagnostic nucleic acid amplification tests (NAAT) and viral load (VL) results. RESULTS: Case 1 had repeat indeterminate NAAT results during the first three weeks of life; repeat testing thereafter was negative with undetectable VL including after daily nevirapine prophylaxis ended. ART was not initiated at this time. Case 2 had a single positive NAAT result at one month of age that prompted initiation of ART. Subsequent results were negative and ART was discontinued. Repeat negative NAAT with VL below the limit of quantification or undetectable continued to be obtained. Shortly after and around weaning, positive NAAT results with high VL (7.1 and 6.03 log(10) copies/ml for Case 1 and 2, respectively) were observed in both children. Both mothers were treated with tenofovir, emtricitabine and efavirenz during breastfeeding. Testing with ultrasensitive assays on early samples conclusively revealed HIV-1 proviral DNA in Case 1. Testing with ultrasensitive assays after the early period but prior to weaning did not detect HIV in either infant. CONCLUSION: We hypothesize that breast milk from the mothers of these two rare cases had HIV-specific or non-specific factors that led to the undetectable results in already infected infants until breastfeeding ended. Our results raise the importance of repeat testing of HIV-exposed breastfed infants after complete cessation of all breastfeeding.

Little is known about how growing up with HIV impacts educational outcomes in sub-Saharan African children. We evaluated if South African children living with HIV (CLWH) were in the appropriate school grade-for-age compared to uninfected control children. We observed higher rates of not being in the correct grade-for-age in CLWH compared with controls (OR 3.32, 95% CI: 2.07-5.34), adjusted for study site, sex, whether the child's biological father was alive, and caregiver education. Initiation of ART before 6 months of age reduced but did not eliminate this association. Whether these associations are due to biological factors or other social and environmental determinants, and how best to support CLWH to achieve educational goals, warrants further investigation.

BACKGROUND: HIV-1 viral load (VL) has been found to be an independent predictor for disease progression among untreated HIV-infected children. However, qualitative polymerase chain reaction (PCR) assays are routinely used for early infant diagnosis (EID). OBJECTIVES: To predict HIV-1 VL at birth using qualitative EID real-time PCR cycle-threshold (Ct) values. STUDY DESIGN: This study was a secondary analysis of results from a cohort of intrauterine HIV-1 infected neonates. Neonates were enrolled at Rahima Moosa Mother & Child Hospital in Johannesburg, South Africa between June 2014 and November 2017. Laboratory EID HIV-1 PCR testing was performed at birth using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test v2.0 (EID CAP/CTM). Some infants had simultaneous EID point-of-care (POC) testing using Xpert HIV-1 Qualitative assay (EID Xpert). Neonates with a confirmed HIV-1 detected EID result and plasma HIV-1 RNA VL test were included in this analysis. Bland-Altman analysis was used to determine extent of agreement between Ct values of both EID assays. Multivariable linear regression models adjusting for time between EID and VL testing were used to describe the association between EID Ct values and VL and to predict VL at given EID Ct values. RESULTS: Among 107 HIV-1 infected neonates included in the study, 59 had POC EID testing. Median VL was 28400 copies per millilitre (cps/ml) (IQR: 1918 – 218358) - two neonates had VL 5.0 log(10)cps/ml in 82.2% (95% CI: 73.9 – 88.3) and 84.7% (95% CI: 73.7 – 91.8) of cases, respectively. CONCLUSION: EID Ct values at birth predict VL and accurately identify infants with VL >5.0 log(10) cps/ml.

Background In the EU funded MARIO project, specific technological tools are adopted for the people living with dementia (PLWD). In the final stage of the project, a validation of the MARIO companion robot was performed from August to October 2017. Objective The aims of the present study are: 1) to illustrate the key results and evidence obtained in the final evaluation phase of the project across the three different pilot sites; 2) to assess the engagement dimensions of the PLWD who interacted with the MARIO robot; and 3) to assess the acceptability and efficacy of the MARIO companion robot on clinical, cognitive, neuropsychiatric, affective and social aspects, resilience, quality of life in PLWD, and burden level of the caregivers. Methods 38 people (M = 14; F = 24) with Alzheimer's disease were screened for eligibility and all were included. The following tests were administered Pre and Post interactions with MARIO: Observational Measurement of Engagement (OME), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Frontal Assessment Battery (FAB), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD), Multidimensional Scale of Perceived Social Support (MSPSS), 14-item Resilience Scale (RS-14), Quality of Life in Alzheimer's Disease (QOL-AD), Caregiver Burden Inventory (CBI), Tinetti Balance Assessment (TBA), and Comprehensive Geriatric Assessment (CGA) was carried out. Results In Post-MARIO interactions, significant improvements were observed in RS-14 (p = 0.020).Considering the age of the people, PLWD with 68-76 years perceived that they had major social support (MSPSS Total: p = 0.016) and friends to support them (MSPSS Fri: p = 0.014). Indeed, the younger people (55-67 years) were less depressed (CSDD: p = 0.033), and more resilient (RS-14: p = 0.003). The people aged 77-85 years perceived they had major family support (MSPSS Fam: p = 0.018). The participants were gender and education matched without any statistically significant difference. Conclusion MARIO may be a useful tool in mitigating depression and loneliness, while enhancing social connectedness, resilience, and overall quality of life for people with dementia.

The current study focuses on the short-term effect of MARIO, a social robot, on quality of life, depression, and perceived social support in persons with dementia (PWD) and evaluates their acceptability of MARIO. Ten PWD in one nursing home took part in a 4-week pilot study, where each participant had up to 12 sessions with MARIO. Sessions comprised engagement in music, news, reminiscence, games, and calendar applications. Standardized questionnaires were administered before and after the 4-week period. Participants had a sustained interest in MARIO during their interactions and an acceptance of MARIO's appearance, sound, and applications. Consequently, participants spent more time socially engaged. No statistically significant differences were found in quality of life, depression, and perceived social support. PWD can engage with a social robot in a real-world nursing home. Future research should incorporate a larger sample and longer intervention period. Funding received from European Union Horizons 2020—The Framework Programme for Research and Innovation (2014–2020) (grant agreement 643808). The authors acknowledge all members of the MARIO Project Advisory Board and the Irish Research Council Government of Ireland Postdoctoral Fellowship scheme (project ID: GOIPD/2017/1301). peer-reviewed 2020-06-25

Vaccinations are a preventative health priority for older adults. The purpose of this paper is to review recent publications on this topic and to provide updates on current research involving recommended vaccines. In the USA, older adults receive vaccinations at less than optimal rates. Vaccine-preventable illnesses, particularly influenza and pneumococcal disease, continue to cause high morbidity and mortality in this population. A recently introduced herpes zoster vaccine has increased efficacy against varicella-zoster virus reactivation and its sequelae. Older adults can benefit from receiving appropriate vaccinations. Interventions to increase rates of vaccination have the potential to improve the overall health of older adults in the USA. Challenges exist in creating and disseminating effective vaccines in this population.

To date, there is a paucity of research conducting natural language processing (NLP) on the open-ended responses of behavior rating scales. Using three NLP lexicons for sentiment analysis of the open-ended responses of the Behavior Assessment System for Children-Third Edition, the researchers discovered a moderately positive correlation between the human composite rating and the sentiment score using each of the lexicons for strengths comments and a slightly positive correlation for the concerns comments made by guardians and teachers. In addition, the researchers found that as the word count increased for open-ended responses regarding the child’s strengths, there was a greater positive sentiment rating. Conversely, as word count increased for open-ended responses regarding child concerns, the human raters scored comments more negatively. The authors offer a proof-of-concept to use NLP-based sentiment analysis of open-ended comments to complement other data for clinical decision making.

Background: Resilience is a process of adapting to stress. For people with dementia, resilience is enhanced through having positive social relationships. Social robots, such as MARIO, can facilitate social engagement. However, the effect of social robots on resilience has not yet been determined. Objective: To investigate how MARIO, a social robot, affects the resilience of people with dementia. Method: Multiple case study methodology was used to explore the resilience of people with dementia during and after they used MARIO in 12 facilitated sessions. Data collection was conducted using: dementia care mapping; semi-structured interviews with people with dementia (n=10), caregivers (n=6), and relatives (n=7); and questionnaires including the Quality of Life in Alzheimer’s disease and The Resilience Scale. During sessions, data was collected using the Observational Measure of Engagement. Data analysis was guided by framework analysis. Qualitative and quantitative data were analysed in NVIVO 12 and SPSS respectively. Then, all data was triangulated in a matrix, analysed for similarities and differences within and across cases, and themes were developed. Results: The cross-case analysis produced four themes: Resilience changes minute to minute; Initiating and maintaining readiness; Active co-creation of meaningful activity; Impact on resilience. The findings revealed that people with dementia required skilled facilitation to use MARIO. During interactions with MARIO, the resilience of eight out of ten people was supported. Sessions with MARIO increased the wellbeing of people with dementia by providing a meaningful activity that re-enforced their positive self-concept. Conclusion: Social robots need to have greater capability to interpret and respond to the emotional needs of users if they are to benefit the resilience of people with dementia without the presence of a supportive facilitator. Future research should explore how strength-based strategies can empower people with dementia to create a meaningful activity using social robots. peer-reviewed

Postmastectomy pain syndrome (PMPS) remains poorly defined, although it is applied to chronic neuropathic pain following surgical procedures of the breast, including mastectomy and lumpectomy in breast-conserving surgery. It is characterized by persistent pain affecting the anterior thorax, axilla, and/or medial upper arm following mastectomy or lumpectomy. Though the onset of pain is most likely to occur after surgery, there may also be a new onset of symptoms following adjuvant therapy, including chemotherapy or radiation therapy. The underlying pathophysiology is likely multifactorial, although exact mechanisms have yet to be elucidated. In this regard, neuralgia of the intercostobrachial nerve is currently implicated as the most common cause of PMPS. Numerous pharmacological options are available in the treatment of PMPS, including gabapentinoids, tricyclic antidepressants, selective serotonin reuptake inhibitors, NMDA receptor antagonists, and nefopam (a non-opioid, non-steroidal benzoxazocine analgesic). Minimally invasive interventional treatment including injection therapy, regional anesthesia, botulinum toxin, and neuromodulation has been demonstrated to have some beneficial effect. A comprehensive update highlighting current perspectives on the treatment of postmastectomy pain syndrome is presented with emphasis on treatments currently available and newer therapeutics currently being evaluated to alleviate this complex and multifactorial condition.

BACKGROUND Younger age at antiretroviral therapy (ART) initiation has been associated with smaller HIV reservoirs. We investigated whether younger age of ART initiation is associated with testing negative and weaker signal on a standard HIV diagnostic test in treated children. METHODS At exit from a longitudinal study at 2 sites in Johannesburg, South Africa, 316 school-aged, HIV-infected children on continuous ART started at a median age of 6.3 months, were tested with standard total nucleic acid PCR used for infant diagnosis. All negative results were repeated. Simultaneous viral load (VL) and CD4 T-cell counts/percentages, along with data collected over the prior 4 years, were used in multivariable regression to predict negative PCR results and higher cycle threshold (Ct) values (weaker signal). RESULTS Seven children (2.2%, 95% confidence interval: 0.6 to 3.8) in the full cohort had negative PCR results; all 7 were in a subset of 102 (6.9%, 95% confidence interval: 2.0 to 11.8) who had initiated ART at age 0-4 months and had VL

Background: Studies in adults and children suggested that starting antiretroviral therapy (ART) soon after infection positively influences early events in HIV infection raising the possibility that remission may be achieved in some. Methods: We designed an analytic treatment interruption (ATI) trial to test the hypothesis that a sizable minority of HIV-infected neonates who initiated ART 30% which were the primary entry criteria for the ATI trial. Proportions achieving ATI eligibility criteria were similar in the 46 infants starting ART

“A Portable Hearth in Great Expectations: Pip’s Search for Home in London” examines Charles Dickens’s uses of kitchen spaces to create and articulate Pip’s search for home, and thus himself. He doe...

BACKGROUND Continuous digital cryotherapy experimentally prevents development and reduces severity of sepsis-associated laminitis. A sleeve style ice boot where ice is in direct contact with the skin, and water drains from the boot is being used clinically for distal limb cryotherapy. The degree of cooling achieved by this boot is unknown. OBJECTIVES Evaluate skin and lamellar cooling after application of the ice sleeve in healthy horses, and the same horses during an endotoxaemia model. STUDY DESIGN Prospective study, crossover design. METHODS In eight healthy horses thermocouples were inserted into dorsal lamellae of both front feet, and under skin on both metacarpi. One forelimb received cryotherapy using sleeve style ice boot, with contralateral limb as control. Temperature was recorded on data logging devices at 5 min intervals during each cryotherapy session. Day 1: temperature data was collected for healthy horses. Day 2: data was collected for the same horses during i.v. administration of endotoxin. RESULTS In healthy and endotoxaemic horses, the sleeve style ice boot significantly decreased mean skin (7.2°C and 5.8°C respectively) and lamellar (10.8°C and 9.6°C respectively) temperatures compared with control limbs (P

Objective Evaluate the analgesic properties and pharmacokinetics of transdermal fentanyl patches (TFPs) in goats. Design Prospective, randomized study. Setting Preclinical Testing Facility at a University Teaching Hospital. Animals Thirty-four adult female Boer-cross goats. Interventions Goats underwent surgery as part of a concurrent orthopedic research study. Twelve hours prior to surgery, each goat received a TFP (target dosage of 2.5 μg/kg/h), or a placebo patch with analgesia provided by buprenorphine (0.01 mg/kg, IM, q 6 h). Patches were removed after 72 hours. Blood was sampled at specified intervals, up to 84 hours following TFP placement. Plasma concentrations of fentanyl (FEN) were determined using liquid chromatography–mass spectrometry. Postoperative pain assessments were performed by two independent blinded observers. Measurements and Main Results TFPs were applied at a mean (± standard deviation, SD) dose of 2.54 ± 0.36 μg/kg/h. No adverse events occurred. Pain scores between TFP and BUP groups were not significantly different at any time point. Mean plasma FEN concentration (± SD) 2 hours following patch application was 1.06 ± 0.85 ng/mL, and remained above 0.5 ng/mL for 40 hours. Maximum mean plasma FEN concentration (Cmax) was 1.84 (ranging from 0.81 to 3.35) ng/mL with average time to maximum concentration (Tmax) of 12 hours after patch application. Conclusions TFP resulted in consistent FEN absorption and plasma concentrations within the human and ovine therapeutic ranges. Pain scores for goats administered TFP were not different than those administered buprenorphine. Ease of administration, duration of analgesia, and decreased dosing frequency make TFPs an attractive option for pain management in goats.

We evaluated bone quality among South African children with HIV (HIV) over a 2-year period by qualitative ultrasound (QUS). Children with HIV have persistently lower bone quality compared with controls reflecting increased porosity, reduced strength and possibly an increased short and long-term risk of fracture.

MARIO is a social robot developed with and for people living with dementia (PLWD) to promote social connectivity and reduce loneliness and isolation by providing access to a number of applications that PLWD can access, via speech and/or touchscreen commands. These applications include My Calendar, which reminds the PLWD about daily schedules and appointments; My Music which provides access to the PLWD s personalised music and My Memories which gives the PLWD the opportunity to reminiscence by showing them photographs of family, friends and/or significant life events. MARIO was developed, tested and evaluated with PLWD in a long stay residential setting over a 13-month period from September 2016 to October 2017. During the first 5 months of MARIO s introduction to PLWD, researchers maintained a reflective practice diary. The aims of the study were twofold: (1) To capture the experiences of researchers of being involved in this process and (2) To help identify strategies to enhance PLWD s engagement with the robot. These reflections were analysed in NVIVO 11.4 using thematic analysis guided by a qualitative descriptive methodology. The following themes emerged from the research: (1) Level of interest in having MARIO present in long-term residential care (LTC), (2) MARIO s appearance and functionalities, (3) Engaging with MARIO, (4) Researchers Recommendations for Introducing Robots in Dementia Care and (5) Impact on researchers. From the researcher s recommendations for introducing robots in dementia care, a number of key strategies were identified which may facilitate the engagement of PLWD with social robots. These include the use of verbal and/or physical prompting by the robot, lack of distraction, and actively engaging staff members or family members when introducing the robot to PLWD. This work highlights the important contribution of reflective practice to the introduction and development of social robots in dementia care. The research leading to these findings have received funding from the European Union Horizon 2020-the Framework Programme for Research and Innovation (2014–2020) under Grant Agreement 643808 Project MARIO ‘Managing active and healthy aging with use of caring service robots’. peer-reviewed 2020-06-14

This study examined behavioral functioning and quality of life in South African children living with perinatally acquired HIV. Compared with controls, children living with perinatally acquired HIV had a higher mean total difficulties score assessed by the Strengths and Difficulties Questionnaire and lower mean quality of life scores assessed by the Pediatric Quality of Life Inventory.

Objective To report surgical complications, occurrence of post-obliteration colic, long term outcome, and return to previous function for horses treated with prosthetic mesh obliteration of the nephrosplenic space. Study Design Retrospective study. Animals Horses (n = 26) having nephrosplenic space obliteration using prosthetic mesh. Methods Horses undergoing mesh obliteration between January 2006 and May 2013 were included. A Proxplast™ mesh was secured to the nephrosplenic space with titanium helical coils in standing horses using laparoscopic technique. Perioperative data were obtained from the medical record and by telephone followup. Tests of proportion were used to compare the study population to the hospital colic population. Occurrence of colic within 1 year of obliteration was compared between horses where the diagnosis was confirmed at laparotomy and those diagnosed by abdominal palpation per rectum using a Fisher's exact test. Results All 26 horses undergoing mesh obliteration during the study period survived to discharge. Long term followup was available for 25 horses, with 23 returning to their previous level of function, and 21 alive at the time of followup. Cause of death was not associated with the surgical procedure in any case. Geldings and Warmbloods were overrepresented compared to the hospital colic population. Ten horses (38%) demonstrated colic after mesh obliteration. All 10 horses were examined by a veterinarian and none were diagnosed with recurrence of nephrosplenic entrapment. Conclusion Mesh obliteration of the nephrosplenic space is an effective alternative to suture closure for preventing nephrosplenic entrapment of the large colon in horses. No complications related to mesh obliteration were reported in our study population.

Background: Studies within trials (SWATs) present an opportunity to examine design factors that may impact on the successful delivery of trials. One area in need of research is trial recruitment. Recruiting patients to trials is a major challenge facing trialists. Failure to meet recruitment targets can result in delays and underpowered studies. This SWAT evaluates the effectiveness of hand-held digital multimedia presentation of trial information and standard written patient information to potential participants on recruitment and retention to a host trial. Methods: This is the protocol for SWAT 15, a two-group, embedded parallel randomised controlled trial (RCT) (ISRCTN12838042) designed within a host trial - the SATIN trial (ISRCTN88111427), a RCT designed for implementation in the Irish primary care setting. The SWAT eligibility criteria was determined by the host trial. General practices who agree to participate in the host trial will provide women (participants) who are willing to consider participating in the host trial with either a multimedia digital information resource facilitated through a handheld tablet device, plus a written participant information leaflet (Intervention) or a written participant information leaflet (comparator). Outcomes are recruitment and retention to the host SATIN trial and participant’s quality of decision-making. Discussion: Although designed to be implemented in a host trial, the host trial, was suspended and therefore this SWAT was not implemented. The protocol and the lessons learnt whilst developing it offer guidance to researchers who wish to answer similar research questions in the future in a similar context or setting. Trial registration: ISRCTN Registry ISRCTN12838042 (11/10/2017)

The prevalence of food allergy in North America is high, and has increased over time. As a result, focus has shifted from treatment to allergy prevention. Previous studies have suggested that hydrolyzed formula may prevent atopic dermatitis in high-risk infants. As a result, multiple international guidelines including the Canadian Paediatric Society (CPS) position statement on allergy prevention recommend the use of hydrolyzed formula as a means of allergy prevention in mothers who are not breastfeeding or using donor breastmilk. However, a recent systematic review has not supported an association between use of hydrolyzed formula and allergy prevention. In addition, studies are emerging supporting the use of early and regular cow’s milk formula as a means of cow’s milk allergy prevention.

Summary Background Initiation of antiretroviral therapy (ART) following diagnosis of HIV infection at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Methods From September, 2013 (era 1), only high-risk HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June, 2014 (era 2), all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October, 2014 (era 3), point of care (POC) diagnostic PCR tests were also done if staff availability allowed. We describe time to ART initiation, mortality, retention in care, and viral suppression among the HIV-infected infants identified across these eras. Findings We tested 5449 HIV-exposed infants who were born between Sept 1, 2013, and June 30, 2016. 88 neonates with confirmed HIV infection were identified and included in the study, of which 86 (98%) started ART. Median age at ART initiation decreased from 9 days (IQR 6–25) in eras 1 and 2 to 2 days (1–8) in era 3. In era 3, more neonates who were co-tested with POC testing started ART within 48 h of birth (29 [83%] of 35; median 1 day [IQR 1–2]) than infants who were not co-tested (one [4%] of 29; median 6 days [5–10]). The probability of mortality by 12 months across the eras was 14% (95% CI 8–24) and did not differ by era. Of the 72 infants who survived and initiated ART at the site, 56 (78%) were retained at 12 months. Of the 56 infants retained in care, 40 (71%) had a viral load less than 400 copies per mL at 12 months, with no differences between eras (p=0·23). Interpretation HIV-infected infants can be identified at birth and ART can be initiated within hours to days. Although most infants in our cohort started ART, mortality remained unacceptably high with suboptimal retention and viral suppression. Reducing mortality and improving retention and viral suppression remain urgent priorities. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Allergy and Infectious Disease, National Institutes of Health, USAID/PEPfAR, and the South African National HIV Programme.

BACKGROUND: Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin meglumine. OBJECTIVES: We hypothesised that treatment of post-surgical SISO horses with firocoxib (COX-2 selective) would reduce the signs of endotoxaemia to a greater extent than flunixin meglumine (nonselective COX inhibitor) while continuing to provide similar levels of pain control. STUDY DESIGN: Blinded randomised clinical trial. METHODS: In addition to clinical monitoring, preoperative and 12-, 24- and 48-h post-operative plasma samples were assessed for prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), TNFα and soluble CD14 (sCD14). RESULTS: In 56 recruited SISO horses, either flunixin meglumine (1.1 mg/kg, i.v., q12h) or firocoxib (0.3 mg/kg, i.v. loading dose; 0.1 mg/kg, i.v., q24h) was given in the post-operative period in three university hospitals from 2015 to 2017. COX-2 selectivity was confirmed by a relative lack of inhibition of the COX-1 prostanoid TXB(2) by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX-2 prostanoid PGE(2). There were no significant differences in pain scores between groups (P = 0.2). However, there was a 3.23-fold increased risk (P = 0.04) of increased plasma sCD14 in horses treated with flunixin meglumine, a validated biomarker of equine endotoxaemia. MAIN LIMITATIONS: Horses were all treated with flunixin meglumine prior to referral. In addition, many horses were treated with lidocaine, which has been shown to mitigate the deleterious effects of flunixin meglumine. CONCLUSIONS: In SISO cases, firocoxib reduced a biomarker of endotoxaemia as compared with flunixin meglumine while continuing to provide similar levels of pain control.

Dementia refers to a group of neuro-degenerative disorders that cause significant impairments to quality of life and difficulties performing activities of daily living. This symposium brings together representatives from four independent international research teams from Europe and the Asia/Pacific region. The speakers bring together perspectives from psychology, computer science, engineering, and nursing, to share the latest research on how robotic technologies may be able to assist people with dementia. The first speaker presents a survey of system requirements to assist a person with early stage of dementia to stay at home, followed by development and testing of service scenarios implemented on a robot. The second speaker focuses on robots that provide cognitive stimulation for people with dementia, and presents results from tests in real world settings with older patients. The third speaker focuses on how companion robots may help relieve the problem of social isolation in people with dementia, with results from a pre-post study on loneliness and quality of life. The last speaker describes a narrative memory companion to assist people with dementia to remember people and events. Together these four separate projects showcase how robots are being developed to assist with different aspects of dementia, and demonstrates results concerning their acceptability and impact when interacting with people.

Vaccines are important for preventing infections in adults aged ≥65 years. Older adults are at increased risk for complications from vaccine-preventable illnesses due to age-associated changes in immune function and chronic medical comorbidities. Vaccination rates for older adults remain low despite widely accepted practice guidelines. Recommended vaccinations for older adults include (1) influenza; (2) pneumococcal; (3) herpes zoster; (4) tetanus, diphtheria, pertussis; and (5) hepatitis B. Cost influences vaccination rates in older adults.

Orthopedic injuries constitute the majority of wounds sustained by U.S. soldiers in recent conflicts. The risk of infection is considerable with fracture fixation devices. In this pilot study, we examined the use of unique bactericidal micron-thin sol-gel films on fracture fixation devices and their ability to prevent and eradicate infections. External fixation was studied with micron-thin sol-gel coated percutaneous pins releasing triclosan and inserted medially into rabbit tibiae. A total of 11 rabbits received percutaneous pins that were either uncoated or sol-gel/triclosan coated. Internal fracture fixation was also studied using sol-gel coated intramedullary (IM) nails releasing vancomycin in the intramedullary tibiae. Six sheep received IM nails that were coated with a sol-gel film that either contained vancomycin or did not contain vancomycin. All animals were challenged with Staphylococcus aureus around the implant. Animals were euthanized at 1 month postoperative. Rabbits receiving triclosan/sol-gel coated percutaneous pins did not show signs of infection. Uncoated percutaneous pins had a significantly higher infection rate. In the sheep study, there were no radiographic signs of osteomyelitis with vancomycin/sol-gel coated IM nails, in contrast to the observations in the control cohort. Hence, the nanostructured sol-gel controlled release technology offers the promise of a reliable and continuous delivery system of bactericidals from orthopedic devices to prevent and treat infection.

Objective—To document causes of colic in equine neonates, evaluate clinical features of neonates managed medically versus surgically, determine short- and long-term survival rates for neonates with specific medical and surgical lesions, and assess ability of patients to achieve intended use. Design—Retrospective case series. Animals—137 client-owned equine neonates (< 30 days old) with a history of colic or signs of colic within 1 hour after hospital admission examined between 2000 and 2010. Procedures—Signalment, history, results of physical examination, laboratory data, ancillary diagnostic tests, details of treatment, primary diagnosis, concurrent diseases and short-term survival rate were obtained from the medical records. Long-term follow-up information was obtained through phone survey. Results—137 neonates with colic were included. The majority (122 [89%]) of neonates were managed medically. The 3 most common diagnoses associated with colic were enterocolitis (37 [27%]), meconium-associated colic (27 [20%]), and transient medical colic (26 [19%]). The most common reason for surgery was small intestinal strangulating obstruction, and these neonates were more likely to have severe, continuous pain and were less responsive to analgesics. Concurrent diseases were common (87 [64%]) but did not significantly impact survival rate. Short-term survival rate was not significantly different between medically (75%) and surgically (73%) managed neonates. Long-term survival rate was excellent (66/71 [93%]) for horses that survived to hospital discharge. Most neonates surviving to maturity were used as intended (49/59 [83%]). Conclusions and Clinical Relevance—Most neonates examined for signs of colic can be managed medically. Short-term survival rate in medically and surgically treated neonates was good. Long-term survival rate of foals discharged from the hospital was excellent, with most achieving intended use.

Hybrid learning is a combination of online learning and face-to-face sessions. This research sought to answer the question, “Can hybrid learning be used to teach working sonographers to perform breast elastography?” A hybrid course was designed titled “Breast Elastography for Working Sonographers.” The course consisted of four online training modules, each complete with a posttest and one face-to-face session. After the face-to-face session lectures, participants were interviewed and observed performing elastography on a breast phantom. Results indicate that in this setting, this method for teaching working sonographers breast elastography is successful.

Modern large frame F, G, & J class gas turbine flow path component design requires the complex integration of multiple design disciplines that traditionally reside with distinct specialists. A traditional design system for an actively cooled gas turbine blade includes aerodynamicists, heat transfer engineers, structural engineers and a failure or lifetime prediction engineers passing information through a manual process with a small number of iterations between the disciplines. Design or manufacturing engineers can also be involved ensuring manufacturability and policing best practices in a predominantly deterministic design system. Over the past few decades robust design or probabilistic design philosophies along with cluster computing advancements have accelerated the release of commercial software that allows for the automation of multiple analytical evaluations at off design points. These software codes allow for process automation of several independent codes executed multiple times at various conditions for automated design of experiment (DOE), and reliability analysis using Monte Carlo or other advanced approximate probabilistic methods across the entire design system. In this paper, the authors are presenting a novel approach of using a commercially available process integration tool to fully integrate a series of other commercially available tools for a root cause failure analysis of a F class turbine blade rather than a new make design. The analysis incorporated a computational fluid dynamics model (CFD) to define inlet temperatures and pressure profiles, a fully conjugate thermal analysis interacting with a finite element (FEA) solver linked to a proprietary creep lifetime prediction model. A DOE was executed to define the meaningful parameters and help rule out potential causes of failure such as loss of coating or compromised cooling system as a contributing factor of the failure which greatly reduced the amount of time and money needed for the investigation. A probabilistic failure analysis was then executed and surrogate models created for quick probabilistic assessment for different operating conditions. This allowed for validation against fleet history to explain the single engine failure not previously observed. Setting up the non-deterministic models initially allowed for rapid redesign in less than 1 month time with confidence that the true root cause was identified and mitigated. It further allowed for feedback and calibrations to the traditional design system methodology.

Fetal alcohol spectrum disorder (FASD) is the leading cause of preventable intellectual disabilities in the United States and a significant public health issue.The purpose of this study is to evaluate the knowledge and screening practices of pre-clinical medical students and clinical providers on FAS, FASD, and alcohol consumption.A short survey sent to medical students and residents on the campus of a large medical school and university hospital.On the survey of clinical providers, 38% of respondents stated they always survey pregnant women about their alcohol consumption, 34% stated they always screen patients planning to get pregnant, and 9% screen women of childbearing age. There were a significant percentage of providers who never screen women. When questioned regarding safe amounts of alcohol consumption during pregnancy, 69% of pre-clinical medical students and 67% of clinical providers stated there is no safe amount of alcohol consumption. Clinical providers were much more likely to correctly select the facial features necessary for the diagnosis (p-value0.01).Significant differences exist in the knowledge and screening practices of these different healthcare providers and trainees. Future interventions should seek to improve knowledge on FAS, FASD, and alcohol consumption, in order for practitioners to be more consistent with national guidelines and the Surgeon General recommendations.

Purpose Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS. Patients and Methods We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response. Results Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS. Conclusion In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.