A Comparison of the Ovulation Method With the CUE Ovulation Predictor in Determining the Fertile Period

The purpose of this study was to compare the CUE Ovulation Predictor with the ovulation method in determining the fertile period. Eleven regularly ovulating women measured their salivary and vaginal electrical resistance (ER) with the CUE, observed their cervical-vaginal mucus, and measured their urine for a luteinizing hormone (LH) surge on a daily basis. Data from 21 menstrual cycles showed no statistical difference (T= 0.33, p= 0.63) between the CUE fertile period, which ranged from 5 to 10 days (mean = 6.7 days, SD = 1.6), and the fertile period of the ovulation method, which ranged from 4 to 9 days (mean = 6.5 days, SD = 2.0). The CUE has potential as an adjunctive device in the learning and use of natural family planning methods

Detection of protein glycosylation using tip enhanced Raman scattering

The correct glycosylation of biopharmaceutical glycoproteins and their formulations is essential for them to have the desired therapeutic effect on the patient. It has recently been shown that Raman spectroscopy can be used to quantify the proportion of glycosylated protein from mixtures of native and glycosylated forms of bovine pancreatic ribonuclease (RNase). Here we show the first steps towards not only the detection of glycosylation status, but the characterisation of glycans themselves from just a few protein molecules at a time using tip-enhanced Raman scattering (TERS). Whilst this technique generates complex data that are very dependent on the protein orientation, with the careful development of combined data preprocessing, univariate and multivariate analysis techniques, we have shown that we can distinguish between the native and glycosylated forms of RNase. Many glycoproteins contain populations of subtly different glycoforms, therefore with stricter orientation control, we believe this has the potential to lead to further glycan characterisation using TERS, which would have use in biopharmaceutical synthesis and formulation research

Long-Term Seizure Suppression and Optogenetic Analyses of Synaptic Connectivity in Epileptic Mice with Hippocampal Grafts of GABAergic Interneurons

Studies in rodent epilepsy models suggest that GABAergic interneuron progenitor grafts can reduce hyperexcitability and seizures in temporal lobe epilepsy (TLE). Although integration of the transplanted cells has been proposed as the underlying mechanism for these disease-modifying effects, prior studies have not explicitly examined cell types and synaptic mechanisms for long-term seizure suppression. To address this gap, we transplanted medial ganglionic eminence (MGE) cells from embryonic day 13.5 VGAT-Venus or VGAT-ChR2-EYFP transgenic embryos into the dentate gyrus (DG) of adult mice 2 weeks after induction of TLE with pilocarpine. Beginning 3–4 weeks after status epilepticus, we conducted continuous video-electroencephalographic recording until 90–100 d. TLE mice with bilateral MGE cell grafts in the DG had significantly fewer and milder electrographic seizures, compared with TLE controls. Immunohistochemical studies showed that the transplants contained multiple neuropeptide or calcium-binding protein-expressing interneuron types and these cells established dense terminal arborizations onto the somas, apical dendrites, and axon initial segments of dentate granule cells (GCs). A majority of the synaptic terminals formed by the transplanted cells were apposed to large postsynaptic clusters of gephyrin, indicative of mature inhibitory synaptic complexes. Functionality of these new inhibitory synapses was demonstrated by optogenetically activating VGAT-ChR2-EYFP-expressing transplanted neurons, which generated robust hyperpolarizations in GCs. These findings suggest that fetal GABAergic interneuron grafts may suppress pharmacoresistant seizures by enhancing synaptic inhibition in DG neural circuits

Localized modes at a D-brane--O-plane intersection and heterotic Alice strings

We study a system of $N_c$ $D3$-branes intersecting $D7$-branes and $O7$-planes in 1+1-dimensions. We use anomaly cancellation and string dualities to argue that there must be chiral fermion zero-modes on the $D3$-branes which are localized near the $O7$-planes. Away from the orientifold limit we verify this by using index theory as well as explicit construction of the zero-modes. This system is related to F-theory on K3 and heterotic matrix string theory, and the heterotic strings are related to Alice string defects in $\mathcal{N}=4$ Super-Yang-Mills. In the limit of large $N_c$ we find an $AdS_3$ dual of the heterotic matrix string CFT.Comment: 44 pages, typos corrected, version published in JHE

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance

INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC). METHODS: We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria. RESULTS: In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006). CONCLUSIONS: Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs

Measuring Coverage in MNCH:A Validation Study Linking Population Survey Derived Coverage to Maternal, Newborn, and Child Health Care Records in Rural China

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future

Scalar soliton quantization with generic moduli

This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credArticle funded by SCOAP3. CP is a Royal Society Research Fellow and partly supported by the U.S. Department of Energy under grants DOE-SC0010008, DOE-ARRA-SC0003883 and DOE-DE-SC0007897. ABR is supported by the Mitchell Family Foundation. We would like to thank the Mitchell Institute at Texas A&M and the NHETC at Rutgers University respectively for hospitality during the course of this work. We would also like to acknowledge the Aspen Center for Physics and NSF grant 1066293 for a stimulating research environment which led to questions addressed in this paper

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein