The use of flow microfluorimetry in the analysis of the phenotype expression of mouse histocompatibility antigens

Quantitation of the expression of cell surface antigens has hitherto been limited to analysis by either cytotoxicity tests or radioimmune assays (5, 15). We report here the use of a new methodology to analyze and quantitate the expression of mouse histocompabililty antigens (H-2 locus) in hybrid clones and parental cell types. The binding of fluorescein-tagged antibody is measured on a cell-to-cell basis in large viable cell populations using flow microfluorimetric techniques. These techniques have been used to measure hapten and immunoglobulin binding to lymphocyte populations (8, 9, 14). However, this is the first report in which these techniques have been used to examine the expression of the H-2 locus. The advantage of this approach is twofold: first, a large and statistically significant sample population may be analyzed one cell at a time, thus revealing the fine detail of heterogeneity in the expression of the cell surface markers within a population. Second, as has been demonstrated for analysis of specific components of the immune system, this method does permit fluorescence-activated sorting of cell types according to their different surface populations (8, 9, 14)

Home ovulation tests and stress in women trying to conceive: a randomized controlled trial.

STUDY QUESTION: Does the use of a digital home ovulation test have any effect on the level of stress in women seeking to conceive? SUMMARY ANSWER: No difference was found in levels of stress between women using digital ovulation tests to time intercourse compared with women who were trying to conceive without any additional aids: in addition, their use did not negatively impact time to conception in users but may provide additional benefits, including an increased understanding of the menstrual cycle, reassurance and confidence in focusing conception attempts to the correct time in the cycle. WHAT IS KNOWN ALREADY: It has been suggested that timing of intercourse in such a way that it coincides with ovulation by using ovulation tests can lead to emotional distress; however, no study has been conducted to investigate this hypothesis specifically, until now. STUDY DESIGN, SIZE AND DURATION: The study was performed over two complete menstrual cycles as a prospective, randomized, controlled trial including quantitative and qualitative methods. The intervention (test) group were given digital ovulation tests to time intercourse to the most fertile time of the cycle and the control group were provided with the current National Institute for Health and Clinical Excellence guidelines for increasing the chances of conception (intercourse every 2-3 days) and asked not to use any additional methods to time when ovulation occurs. PARTICIPANTS/MATERIALS, SETTING AND METHODS: A total of 210 women who were seeking to conceive were recruited from the general UK population. A total of 115 women were randomized to the test group and 95 to the control group through block randomization. The positive and negative affect schedule (PANAS) and the Perceived Stress Scale (PSS) were used to measure subjective stress levels, the Short-Form 12 health survey was used as a measure of general health and well-being and urine samples were measured for biochemical markers of stress including urinary cortisol. Qualitative data were collected in the form of a telephone interview upon study completion. MAIN RESULTS AND THE ROLE OF CHANCE: There was no evidence for a difference either in total stress as measured using the PSS or in total positive or negative affect using the PANAS questionnaire between the test and control groups at any time point for the duration of the study. During cycle 1, for example, on Day 6, the difference in total stress score (test-control) was -0.62 [95% confidence interval (CI) -2.47 to 1.24] and on the day of the LH surge, it was 0.53 (95% CI -1.38 to 2.44). In addition, no correlation was observed between time trying to conceive and levels of stress, or between age and levels of stress, and no evidence was found to show that stress affected whether or not a pregnancy was achieved. There is also no evidence that the biochemistry measurements are related to whether a pregnancy was achieved or of a difference in biochemistry between the treatment groups. The use of digital ovulation tests did not negatively affect time to conception and with an adequately sized study, could potentially show improvement. To ensure that the results of this study were not affected by chance, we used a number of different methods for measuring stress, each of which had been independently validated. LIMITATIONS AND REASONS FOR CAUTION: Randomization occurred before the start of the study because of the need to provide the ovulation tests in readiness for Day 6 of the first cycle. As a consequence, a number of women fell pregnant during this period (22 and 13 in the test and control groups, respectively). A further 15 women were either lost to follow-up or withdrew consent prior to study start. Pregnancy rate was higher overall in the test group, so to ensure that there were sufficient data from women who failed to become pregnant in the test group, we implemented an additional biased recruitment. This second cohort may have been different from the first, although no significant differences were observed between the two phases of recruitment for any of the information collected upon admission to the study. WIDER IMPLICATIONS OF THE FINDINGS: Women who seek medical advice while trying to conceive should not be discouraged by health care professionals from using digital ovulation tests in order to time intercourse. The cohort of women recruited to this study initially had no evidence of infertility and were looking to conceive in a non-medical setting. A separate study to assess the impact of home ovulation tests in a subfertile population would be of interest and complementary to the present study. STUDY FUNDING/COMPETING INTERESTS: This study was funded by SPD Swiss Precision Diagnostics, GmbH, manufacturer of Clearblue(®) pregnancy and ovulation tests. SPD Development Company Ltd is a wholly owned subsidiary of SPD Swiss Precision Diagnostics GmbH; together referred to as SPD. TRIAL REGISTRATION NUMBER: NCT01084304 (www.clinicaltrials.gov)

Do South Asian women with PCOS have poorer health-related quality of life than Caucasian women with PCOS? A comparative cross-sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disorder affecting women of reproductive age. This study aimed to compare the HRQoL of South Asian and white Caucasian women with PCOS, given that it is particularly common among women of South Asian origin and they have been shown to have more severe symptoms. METHODS: The Polycystic Ovary Syndrome Questionnaire (PCOSQ) and the Short Form-36 (SF-36) were administered in a cross-sectional survey to 42 South Asian and 129 Caucasian women diagnosed with PCOS recruited from the gynaecology outpatient clinics of two university teaching hospitals in Sheffield and Leeds. Additional clinical data was abstracted from medical notes. Normative data, collected as part of the Oxford Health and Lifestyles II survey, was obtained to compare SF-36 results with ethnically matched women from the general UK population. Using the SF-36, normative HRQoL scores for women of South Asian origin were lower than for Caucasian women. Given this lower baseline we tested whether the same relationship holds true among those with PCOS. RESULTS: Although HRQoL scores for women with PCOS were lower than normative data for both groups, South Asian women with PCOS did not have poorer HRQoL than their Caucasian counterparts. For both the SF-36 and PCOSQ, mean scores were broadly the same for both Asian and Caucasian women. For both groups, the worst two HRQoL domains as measured on the PCOSQ were 'infertility' and 'weight', with respective scores of 35.3 and 42.3 for Asian women with PCOS compared to 38.6 and 35.4 for Caucasian women with PCOS. The highest scoring domain for South Asian women with PCOS was 'menstrual problems' (55.3), indicating best health, and was the only statistically significant difference from Caucasian women (p = 0.01). On the SF-36, the lowest scoring domain was 'Energy & Vitality' for Caucasian women with PCOS, but this was significantly higher for Asian women with PCOS (p = 0.01). The best health status for both groups was 'physical functioning', although this was significantly lower for South Asian women with PCOS (p = 0.005). Interestingly, only two domains differed significantly from the normative data for the Asian women with PCOS, while seven domains were significantly different for the Caucasian women with PCOS compared to their normative counterparts. CONCLUSIONS: The HRQoL differences that exist between South Asian and Caucasian women in the general population do not appear to be replicated amongst women with PCOS. PCOS reduces HRQoL to broadly similar levels, regardless of ethnicity and differences in the normative baseline HRQoL of these groups

Delusional beliefs and reason giving

Delusions are often regarded as irrational beliefs, but their irrationality is not sufficient to explain what is pathological about them. In this paper we ask whether deluded subjects have the capacity to support the content of their delusions with reasons, that is, whether they can author their delusional states. The hypothesis that delusions are characterised by a failure of authorship, which is a dimension of self knowledge, deserves to be empirically tested because (a) it has the potential to account for the distinction between endorsing a delusion and endorsing a framework belief; (b) it contributes to a philosophical analysis of the relationship between rationality and self knowledge; and (c) it informs diagnosis and therapy in clinical psychiatry. However, authorship cannot provide a demarcation criterion between delusions and other irrational belief states

Giant QCD K-factors beyond NLO

Hadronic observables in Z+jet events can be subject to large NLO corrections at TeV scales, with K-factors that even reach values of order 50 in some cases. We develop a method, LoopSim, by which approximate NNLO predictions can be obtained for such observables, supplementing NLO Z+jet and NLO Z+2-jet results with a unitarity-based approximation for missing higher loop terms. We first test the method against known NNLO results for Drell-Yan lepton pt spectra. We then show our approximate NNLO results for the Z+jet observables. Finally we examine whether the LoopSim method can provide useful information even in cases without giant K-factors, with results for observables in dijet events that can be compared to early LHC data.Comment: 38 pages, 13 figures; v2 includes additional reference

Maverick dark matter at colliders

Assuming that dark matter is a weakly interacting massive particle (WIMP) species X produced in the early Universe as a cold thermal relic, we study the collider signal of pp or ppbar -> XXbar + jets and its distinguishability from standard-model background processes associated with jets and missing energy. We assume that the WIMP is the sole particle related to dark matter within reach of the LHC--a "maverick" particle--and that it couples to quarks through a higher dimensional contact interaction. We simulate the WIMP final-state signal XXbar + jet and dominant standard-model (SM) background processes and find that the dark-matter production process results in higher energies for the colored final state partons than do the standard-model background processes, resulting in more QCD radiation and a higher jet multiplicity. As a consequence, the detectable signature of maverick dark matter is an excess over standard-model expectations of events consisting of large missing transverse energy, together with large leading jet transverse momentum and scalar sum of the transverse momenta of the jets. Existing Tevatron data and forthcoming LHC data can constrain (or discover!) maverick dark matter.Comment: 11 pages, 7 figure

Supervised machine learning algorithms can classify open-text feedback of doctor performance with human-level accuracy

Background: Machine learning techniques may be an effective and efficient way to classify open-text reports on doctor’s activity for the purposes of quality assurance, safety, and continuing professional development. Objective: The objective of the study was to evaluate the accuracy of machine learning algorithms trained to classify open-text reports of doctor performance and to assess the potential for classifications to identify significant differences in doctors’ professional performance in the United Kingdom. Methods: We used 1636 open-text comments (34,283 words) relating to the performance of 548 doctors collected from a survey of clinicians’ colleagues using the General Medical Council Colleague Questionnaire (GMC-CQ). We coded 77.75% (1272/1636) of the comments into 5 global themes (innovation, interpersonal skills, popularity, professionalism, and respect) using a qualitative framework. We trained 8 machine learning algorithms to classify comments and assessed their performance using several training samples. We evaluated doctor performance using the GMC-CQ and compared scores between doctors with different classifications using t tests. Results: Individual algorithm performance was high (range F score=.68 to .83). Interrater agreement between the algorithms and the human coder was highest for codes relating to “popular” (recall=.97), “innovator” (recall=.98), and “respected” (recall=.87) codes and was lower for the “interpersonal” (recall=.80) and “professional” (recall=.82) codes. A 10-fold cross-validation demonstrated similar performance in each analysis. When combined together into an ensemble of multiple algorithms, mean human-computer interrater agreement was .88. Comments that were classified as “respected,” “professional,” and “interpersonal” related to higher doctor scores on the GMC-CQ compared with comments that were not classified (P.05). Conclusions: Machine learning algorithms can classify open-text feedback of doctor performance into multiple themes derived by human raters with high performance. Colleague open-text comments that signal respect, professionalism, and being interpersonal may be key indicators of doctor’s performance

‘The phoenix that always rises from the ashes’: an exploratory qualitative study of the experiences of an initiative informed by principles of psychological first aid following the Beirut blast

BACKGROUND: On 4 August 2020, an explosion occurred in Beirut, Lebanon. Hundreds of people were killed, thousands injured and displaced. An initiative was rapidly initiated to provide remote support informed by psychological first aid for the mental health of Lebanese young adults affected by the blast. However, little is known about recipients’ experiences of such initiatives. OBJECTIVES: This study aimed to qualitatively explore the experiences of supporters and recipients in the community-led initiative following the blast. METHOD: We recruited a diverse sample of four supporters and four Lebanese recipients who took part in the Beirut initiative. Semi-structured interviews were conducted with participants. Reflexive thematic analysis was used to analyse the qualitative data. RESULTS: We developed five themes from the qualitative interviews, which highlighted ideas around accessibility, alienation, the relationship, elements of the safe space created by the initiative, and unmet needs and areas for improvement. Recipients described the detrimental impact of the blast on their mental health within the Lebanese context and beyond. Recipients and supporters elucidated complex experiences of the support and its impact. CONCLUSIONS: Our findings suggest remote support has the potential to be acceptable for young adults in Lebanon. Further research into support informed by psychological first aid after similar crisis events is warranted

Vector boson pair production at the LHC

We present phenomenological results for vector boson pair production at the LHC, obtained using the parton-level next-to-leading order program MCFM. We include the implementation of a new process in the code, pp -> \gamma\gamma, and important updates to existing processes. We incorporate fragmentation contributions in order to allow for the experimental isolation of photons in \gamma\gamma, W\gamma, and Z\gamma production and also account for gluon-gluon initial state contributions for all relevant processes. We present results for a variety of phenomenological scenarios, at the current operating energy of \sqrt{s} = 7 TeV and for the ultimate machine goal, \sqrt{s} = 14 TeV. We investigate the impact of our predictions on several important distributions that enter into searches for new physics at the LHC.Comment: 35 pages, 14 figure

Multiple Parton Interactions in Z+jets production at the LHC. A comparison of factorized and non--factorized double parton distribution functions

We examine the contribution of Multiple Parton Interactions to Z+n-jets production at the LHC, n=2,3,4, where the Z boson is assumed to decay leptonically. We compare the results obtained with the correlated GS09 double parton distribution function with those obtained with two instances of fully factorized single parton distribution functions: MSTW2008LO and CTEQ6LO. It appears quite feasible to measure the MPI contribution to Z+2/3/4 jets already in the first phase of the LHC with a total luminosity of one inverse femtobarn at 7 TeV. If as expected the trigger threshold for single photons is around 80 GeV, Z+2-jets production may well turn out to be more easily observable than the gamma+3-jets channel. The MPI cross section is dominated by relatively soft events with two jets balancing in transverse momentum.Comment: 15 pages, 3 plot