Site Visit Frequency Policies for Mobile Family Planning Services

Improving access to family planning services is key to achieving many of the United Nations sustainable development goals. To scale up access in remote areas and urban slums, many developing countries deploy mobile family planning teams that visit “outreach sites” several times per year. Visit frequencies have a significant effect on the total number of clients served and hence the impact of the outreach program. Using a large dataset of visits in Madagascar, Uganda and Zimbabwe, our study models the relationship between the number of clients seen during a visit and the time since the last visit and uses this model to analyse the characteristics of optimal frequencies. We use the latter to develop simple frequency policies for practical use, prove bounds on the worst-case optimality gap, and test the impact of the policies with a simulation model. Our main finding is that despite the complexity of the frequency optimisation problem, simple policies yield near-optimal results. This holds even when few data are available and when the relationship between client volume and the time since the last visit is misspecified or substantially biased. The simulation for Uganda shows a potential increase in client numbers of between 7% and 10%, which corresponds to more than 12,000 additional families to whom family planning services could be provided.

Functional properties of measles virus proteins derived from a subacute sclerosing panencephalitis patient who received repeated remdesivir treatments

Subacute sclerosing panencephalitis (SSPE) is a rare but fatal late neurological complication of measles, caused by persistent measles virus (MeV) infection of the central nervous system. There are no drugs approved for the treatment of SSPE. Here, we followed the clinical progression of a 5-year-old SSPE patient after treatment with the nucleoside analog remdesivir, conducted a post-mortem evaluation of the patient’s brain, and characterized the MeV detected in the brain. The quality of life of the patient transiently improved after the first two courses of remdesivir, but a third course had no further clinical effect, and the patient eventually succumbed to his condition. Post-mortem evaluation of the brain displayed histopathological changes including loss of neurons and demyelination paired with abundant presence of MeV RNA-positive cells throughout the brain. Next-generation sequencing of RNA isolated from the brain revealed a complete MeV genome with mutations that are typically detected in SSPE, characterized by a hypermutated M gene. Additional mutations were detected in the polymerase (L) gene, which were not associated with resistance to remdesivir. Functional characterization showed that mutations in the F gene led to a hyperfusogenic phenotype predominantly mediated by N465I. Additionally, recombinant wild-type-based MeV with the SSPE-F gene or the F gene with the N465I mutation was no longer lymphotropic but instead efficiently disseminated in neural cultures. Altogether, this case encourages further investigation of remdesivir as a potential treatment of SSPE and highlights the necessity to functionally understand SSPE-causing MeV.</p

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data

We report a quasi-differential upper limit on the extremely-high-energy (EHE) neutrino flux above $5\times 10^{6}$ GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above $10^{6}$ GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between $5 \times 10^{6}$ and $5 \times 10^{10}$ GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\ {\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}$at$10^9\ {\rm GeV}$. A significant part of the parameter-space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review

Optical imaging of the peri-tumoral inflammatory response in breast cancer

<p>Abstract</p> <p>Purpose</p> <p>Peri-tumoral inflammation is a common tumor response that plays a central role in tumor invasion and metastasis, and inflammatory cell recruitment is essential to this process. The purpose of this study was to determine whether injected fluorescently-labeled monocytes accumulate within murine breast tumors and are visible with optical imaging.</p> <p>Materials and methods</p> <p>Murine monocytes were labeled with the fluorescent dye DiD and subsequently injected intravenously into 6 transgenic MMTV-PymT tumor-bearing mice and 6 FVB/n control mice without tumors. Optical imaging (OI) was performed before and after cell injection. Ratios of post-injection to pre-injection fluorescent signal intensity of the tumors (MMTV-PymT mice) and mammary tissue (FVB/n controls) were calculated and statistically compared.</p> <p>Results</p> <p>MMTV-PymT breast tumors had an average post/pre signal intensity ratio of 1.8+/- 0.2 (range 1.1-2.7). Control mammary tissue had an average post/pre signal intensity ratio of 1.1 +/- 0.1 (range, 0.4 to 1.4). The p-value for the difference between the ratios was less than 0.05. Confocal fluorescence microscopy confirmed the presence of DiD-labeled cells within the breast tumors.</p> <p>Conclusion</p> <p>Murine monocytes accumulate at the site of breast cancer development in this transgenic model, providing evidence that peri-tumoral inflammatory cell recruitment can be evaluated non-invasively using optical imaging.</p

Effect of thrombin peptide 508 (TP508) on bone healing during distraction osteogenesis in rabbit tibia

Thrombin-related peptide 508 (TP508) accelerates bone regeneration during distraction osteogenesis (DO). We have examined the effect of TP508 on bone regeneration during DO by immunolocalization of Runx2 protein, a marker of osteoblast differentiation, and of osteopontin (OPN) and bone sialoprotein (BSP), two late markers of the osteoblast lineage. Distraction was performed in tibiae of rabbits over a period of 6 days. TP508 (30 or 300 μg) or vehicle was injected into the distraction gap at the beginning and end of the distraction period. Two weeks after active distraction, tissue samples were harvested and processed for immunohistochemical analysis. We also tested the in vitro effect of TP508 on Runx2 mRNA expression in osteoblast-like (MC3T3-E1) cells by polymerase chain reaction analysis. Runx2 and OPN protein were observed in preosteoblasts, osteoblasts, osteocytes of newly formed bone, blood vessel cells and many fibroblast-like cells of the soft connective tissue. Immunostaining for BSP was more restricted to osteoblasts and osteocytes. Significantly more Runx2- and OPN-expressing cells were seen in the group treated with 300 μg TP508 than in the control group injected with saline or with 30 μg TP508. However, TP508 failed to increase Runx2 mRNA levels significantly in MC3T3-E1 cells after 2–3 days of exposure. Our data suggest that TP508 enhances bone regeneration during DO by increasing the proportion of cells of the osteoblastic lineage. Clinically, TP508 may shorten the healing time during DO; this might be of benefit when bone regeneration is slow

Blood pressure self-monitoring in pregnancy (BuMP) feasibility study; a qualitative analysis of women's experiences of self-monitoring

Background Hypertensive disorders in pregnancy are a leading cause of maternal and fetal morbidity worldwide. Raised blood pressure (BP) affects 10% of pregnancies worldwide, of which almost half develop pre-eclampsia. The proportion of pregnant women who have risk factors for pre-eclampsia (such as pre-existing hypertension, obesity and advanced maternal age) is increasing. Pre-eclampsia can manifest itself before women experience symptoms and can develop between antenatal visits. Incentives to improve early detection of gestational hypertensive disorders are therefore strong and self-monitoring of blood pressure (SMBP) in pregnancy might be one means to achieve this, whilst improving women’s involvement in antenatal care. The Blood Pressure Self-Monitoring in Pregnancy (BuMP) study aimed to evaluate the feasibility and acceptability of SMBP in pregnancy. Methods To understand women’s experiences of SMBP during pregnancy, we undertook a qualitative study embedded within the BuMP observational feasibility study. Women who were at higher risk of developing hypertension and/or pre-eclampsia were invited to take part in a study using SMBP and also invited to take part in an interview. Semi-structured interviews were conducted at the women’s homes in Oxfordshire and Birmingham with women who were self-monitoring their BP as part of the BuMP feasibility study in 2014. Interviews were conducted by a qualitative researcher and transcribed verbatim. A framework approach was used for analysis. Results Fifteen women agreed to be interviewed. Respondents reported general willingness to engage with monitoring their own BP, feeling that it could reduce anxiety around their health during pregnancy, particularly if they had previous experience of raised BP or pre-eclampsia. They felt able to incorporate self-monitoring into their weekly routines, although this was harder post-partum. Self-monitoring of BP made them more aware of the risks of hypertension and pre-eclampsia in pregnancy. Feelings of reassurance and empowerment were commonly reported by the women in our sample

Testing the potential of a virtual reality neurorehabilitation system during performance of observation, imagery and imitation of motor actions recorded by wireless functional near-infrared spectroscopy (fNIRS)

Background Several neurorehabilitation strategies have been introduced over the last decade based on the so-called simulation hypothesis. This hypothesis states that a neural network located in primary and secondary motor areas is activated not only during overt motor execution, but also during observation or imagery of the same motor action. Based on this hypothesis, we investigated the combination of a virtual reality (VR) based neurorehabilitation system together with a wireless functional near infrared spectroscopy (fNIRS) instrument. This combination is particularly appealing from a rehabilitation perspective as it may allow minimally constrained monitoring during neurorehabilitative training. Methods fNIRS was applied over F3 of healthy subjects during task performance in a virtual reality (VR) environment: 1) 'unilateral' group (N = 15), contralateral recording during observation, motor imagery, observation & motor imagery, and imitation of a grasping task performed by a virtual limb (first-person perspective view) using the right hand; 2) 'bilateral' group (N = 8), bilateral recording during observation and imitation of the same task using the right and left hand alternately. Results In the unilateral group, significant within-condition oxy-hemoglobin concentration Δ[O2Hb] changes (mean ± SD μmol/l) were found for motor imagery (0.0868 ± 0.5201 μmol/l) and imitation (0.1715 ± 0.4567 μmol/l). In addition, the bilateral group showed a significant within-condition Δ[O2Hb] change for observation (0.0924 ± 0.3369 μmol/l) as well as between-conditions with lower Δ[O2Hb] amplitudes during observation compared to imitation, especially in the ipsilateral hemisphere (p < 0.001). Further, in the bilateral group, imitation using the non-dominant (left) hand resulted in larger Δ[O2Hb] changes in both the ipsi- and contralateral hemispheres as compared to using the dominant (right) hand. Conclusions This study shows that our combined VR-fNIRS based neurorehabilitation system can activate the action-observation system as described by the simulation hypothesis during performance of observation, motor imagery and imitation of hand actions elicited by a VR environment. Further, in accordance with previous studies, the findings of this study revealed that both inter-subject variability and handedness need to be taken into account when recording in untrained subjects. These findings are of relevance for demonstrating the potential of the VR-fNIRS instrument in neurofeedback applications