Mobile phone-delivered reminders and incentives to improve childhood immunisation coverage and timeliness in Kenya (M-SIMU): a cluster randomised controlled trial

Background As mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya. Methods In this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES = USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with logbinomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with ClinicalTrials.gov, number NCT01878435. Findings Between Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1·09, 95% CI 1·02–1·16, p=0·014) than children in the control group. Interpretation In a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%

The readiness, need for, and effect of mhealth interventions to improve immunization timeliness and coverage in rural western Kenya

Background: As mobile phone ownership levels grow globally, opportunities to target hard-to-reach populations through mobile-health technologies become more realistic. In a rural Kenyan population, this dissertation seeks to assess the magnitude and risk factors of immunization timeliness and coverage, to determine the readiness of a community for mHealth interventions by assessing prevalence and risk factors for mobile phone ownership and SMS utilization, and to assess the effect of the Mobile Solutions for Immunization (M-SIMU) cluster randomized controlled trial. Methods: A cross-sectional survey of Kenyan caregivers was conducted to collect baseline immunization and mobile phone ownership estimates for M-SIMU. Predictors of mobile phone ownership were obtained through multivariable logistic regression. Risk factors for delayed immunizations and not receiving immunization were calculated using binomial regression with log link. The M-SIMU trial randomized villages to four arms: Control, short message system (SMS) reminders only, SMS reminders + 75 Kenyan Schillings (KSH) incentive or, SMS reminders + 200 KSH incentive. Inverse Kaplan-Meier curves and Cox regressions assessed the intervention’s effect on pentavalent3 and measles vaccination. Results: Older maternal age, higher maternal literacy and education, smaller households, and higher socioeconomic status were associated with phone ownership. Immunization coverage for the third dose of pentavalent vaccine (pentavalent3), measles, and fully immunized children (FIC) were 95%, 83%, and 80%, respectively. Delayed pentavalent1 was associated with not receiving pentavalent3 (RR: 5.61; 95%CI: 3.77-8.33), measles vaccine (RR: 1.51; 95%CI: 1.15-1.99), and FIC (RR: 1.87; 95%CI: 1.51-2.32). The prevalence of delayed pentavalent1, pentavalent3, and measles were 11%, 24%, and 29%, respectively. No common risk factors in the delay models were found. For M-SIMU, Kaplan-Meier curves found significant differences across arms in time to pentavalent3 (p<0.01) but not measles vaccination (p=0.10). SMS + 200 KSH infants were associated with pentavalent3 vaccination (HR: 3.33; 95%CI: 1.71-6.47) and approached significance for measles (HR: 2.05; 95%CI: 0.95-4.41; p=0.07), as compared to controls. The SMS only and SMS plus 75KSH were not significantly associated with either vaccine. Conclusions: In a population with moderate phone ownership, high immunization coverage, and moderate vaccine delays, SMS reminders plus 200KSH improved pentavalent3 vaccination

Children’s services in the age of information technology: What matters most to frontline professionals

Summary The last two decades have seen information systems featuring prominently in calls for the modernisation of the UK social care system. However, critics have maintained that these systems are of limited value to social care professionals whose design and implementation is driven by a preoccupation with performance management and a culture of professional audit and accountability, precepts of 'managerialism'. However, this area of research has often suffered from lack of focus on how technological changes affect public administration and service delivery and often characterises technology as a politically neutral tool detached from its socio-political context whilst also ignoring the strategic predispositions of human service professionals.Findings This research was conducted in three local authorities in England. Using the 'technological affordance' perspective, we contend that the way social workers interact with Integrated Children's System is shaped by the discord between socio-historically evolved professional values epitomising the social work profession and managerialist reforms promoting standardised ways of performing it. Application Integrated Children's System has transformed social work from an art to a technical activity, dominated by unimaginative and routinised working practices. Social workers are becoming peripheral figures and this is where social work needs to be reclaimed. Policymakers need to rethink taken for granted assumptions that practitioners would replace their professional expertise with technology and realise that the effective use of Integrated Children's System depends on bureau-professionalised judgements of social workers. Whilst specific patterns of technology usage can be developed and institutionalised, real objectives of children's social services should not be sacrificed

Construction of a Global Pain Systems Network Highlights Phospholipid Signaling as a Regulator of Heat Nociception

The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species. © 2012 Neely et al

A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors

Host proteins are essential for HIV entry and replication and can be important nonviral therapeutic targets. Large-scale RNA interference (RNAi)-based screens have identified nearly a thousand candidate host factors, but there is little agreement among studies and few factors have been validated. Here we demonstrate that a genome-wide CRISPR-based screen identifies host factors in a physiologically relevant cell system. We identify five factors, including the HIV co-receptors CD4 and CCR5, that are required for HIV infection yet are dispensable for cellular proliferation and viability. Tyrosylprotein sulfotransferase 2 (TPST2) and solute carrier family 35 member B2 (SLC35B2) function in a common pathway to sulfate CCR5 on extracellular tyrosine residues, facilitating CCR5 recognition by the HIV envelope. Activated leukocyte cell adhesion molecule (ALCAM) mediates cell aggregation, which is required for cell-to-cell HIV transmission. We validated these pathways in primary human CD4 + T cells through Cas9-mediated knockout and antibody blockade. Our findings indicate that HIV infection and replication rely on a limited set of host-dispensable genes and suggest that these pathways can be studied for therapeutic intervention

A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism

<p>Abstract</p> <p>Background</p> <p>Opioids are the most widely used analgesics for the treatment of clinical pain. They produce their therapeutic effects by binding to μ-opioid receptors (MORs), which are 7 transmembrane domain (7TM) G-protein-coupled receptors (GPCRs), and inhibiting cellular activity. However, the analgesic efficacy of opioids is compromised by side-effects such as analgesic tolerance, dependence and opioid-induced hyperalgesia (OIH). In contrast to opioid analgesia these side effects are associated with cellular excitation. Several hypotheses have been advanced to explain these phenomena, yet the molecular mechanisms underlying tolerance and OIH remain poorly understood.</p> <p>Results</p> <p>We recently discovered a new human alternatively spliced isoform of MOR (MOR1K) that is missing the N-terminal extracellular and first transmembrane domains, resulting in a 6TM GPCR variant. To characterize the pattern of cellular transduction pathways activated by this human MOR1K isoform, we conducted a series of pharmacological and molecular experiments. Results show that stimulation of MOR1K with morphine leads to excitatory cellular effects. In contrast to stimulation of MOR1, stimulation of MOR1K leads to increased Ca²⁺levels as well as increased nitric oxide (NO) release. Immunoprecipitation experiments further reveal that unlike MOR1, which couples to the inhibitory Gα_i/ocomplex, MOR1K couples to the stimulatory Gα_scomplex.</p> <p>Conclusion</p> <p>The major MOR1 and the alternative MOR1K isoforms mediate opposite cellular effects in response to morphine, with MOR1K driving excitatory processes. These findings warrant further investigations that examine animal and human MORK1 expression and function following chronic exposure to opioids, which may identify MOR1K as a novel target for the development of new clinically effective classes of opioids that have high analgesic efficacy with diminished ability to produce tolerance, OIH, and other unwanted side-effects.</p

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Evaluating the Impact of the Clean Heat Program on Air Pollution Levels in New York City

Residual heating oil is a class of heavy oil that remains after the lighter components are distilled away from crude oil in the refining process (EIA 2020) and has been linked to adverse health outcomes (Bell et al. 2009). In New York City (NYC), residual heating oil has been identified as a major source of multiple air pollutants, including fine particulate matter [PM less than or equal to 2.5 micrometers ≤ 2.5 μm in aerodynamic diameter (PM₂.₅)] (Clougherty et al. 2010; Kheirbek et al. 2014), sulfur dioxide (SO₂), nitrogen oxides (NOₓ) (U.S. EPA 1998), and black carbon (Cornell et al. 2012). Prior to policy implementation, three types of heating oil were used in NYC: heating oil #4, #6, and ultra-low sulfur oil #2. Both #6 and #4 are referred to as residual heating oils, and oil #2, which is the lightest of the three, has been considered a cleaner alternative (Kheirbek et al. 2014). In 2012, NYC established the Clean Heat Program (CHP) to eliminate the use of residual heating oil and move toward cleaner energy forms (Hernández 2016). Here, we have evaluated the CHP outcomes, quantified the CHP-attributable air pollution reductions between 2012 and 2016, and assessed if and how these reductions vary by neighborhood socioeconomic status (SES). We aim to contribute to the knowledge of CHP effects since its implementation, assess relevant equity issues, and inform future policy improvements

Facial pain with localized and widespread manifestations: Separate pathways of vulnerability

Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically-relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically-homogenous subtypes of complex diseases. We report findings from a case-control, genetic association study of relationships between 2,925 SNPs and two subtypes of a commonly occurring chronic facial pain condition, temporomandibular disorder (TMD): 1) localized TMD; and 2) TMD with widespread pain. When compared to healthy controls, cases with localized TMD differed in allelic frequency of SNPs that mapped to a serotonergic receptor pathway (P=0.0012), while cases of TMD with widespread pain differed in allelic frequency of SNPs that mapped to a T-cell receptor pathway (P=0.0014). A risk index representing combined effects of six SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio = 2.7, P=1.3×10−9), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio = 1.6, P=0.014). A risk index representing combined effects of eight SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P=1.9×10−8), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background

Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study

Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously-reported associations between TMD and two genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD and they identify potential targets for therapeutic intervention