Dual specificity antibodies using a double-stranded oligonucleotide bridge

AbstractThe covalent conjugation of oligonucleotides to antibody Fab’ fragments was optimized by using oligonucleotides modified with a hexaethylene linker arm bearing three amino groups. One oligonucleotide was coupled to antibody of one specificity and a complementary oligonucleotide to antibody of a second specificity. The antibodies were then allowed to hybridize by base pairing of the complementary nucleotide sequences and the generation of bispecific antibody was analyzed on SDS-PAGE and confirmed using BIAcore analysis. The strategy of complementary oligonucleotide-linked bispecific molecules is not limited to antibodies but is applicable to linking any two molecules of different characteristics

Superallowed 0+ to 0+ nuclear beta decays: A new survey with precision tests of the conserved vector current hypothesis and the standard model

A new critical survey is presented of all half-life, decay-energy and branching-ratio measurements related to 20 0+ to 0+ beta decays. Compared with our last review, there are numerous improvements: First, we have added 27 recently published measurements and eliminated 9 references; of particular importance, the new data include a number of high-precision Penning-trap measurements of decay energies. Second, we have used the recently improved isospin symmetry-breaking corrections. Third, our calculation of the statistical rate function now accounts for possible excitation in the daughter atom. Finally, we have re-examined the systematic uncertainty associated with the isospin symmetry-breaking corrections by evaluating the radial-overlap correction using Hartree-Fock radial wave functions and comparing the results with our earlier calculations, which used Saxon-Woods wave functions; the provision for systematic uncertainty has been changed as a consequence. The new corrected Ft values are impressively constant and their average, when combined with the muon liftime, yields the up-down quark-mixing element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix, V_{ud} = 0.97425(22). The unitarity test on the top row of the matrix becomes |V_{ud}|^2 + |V_{us}|^2 + |V_{ub}|^2 = 0.99995(61). Both V_{ud} and the unitarity sum have significantly reduced uncertainties compared with our previous survey, although the new value of V_{ud} is statistically consistent with the old one. From these data we also set limits on the possible existence of scalar interactions, right-hand currents and extra Z bosons. Finally, we discuss the priorities for future theoretical and experimental work with the goal of making the CKM unitarity test even more definitive.Comment: 36 pages, 11 tables, 9 figure

Superallowed nuclear beta decays: A critical survey with tests of CVC and the standard model

A complete and critical survey is presented of all half-life, decay-energy and branching-ratio measurements related to 20 superallowed decays; no measurements are ignored, though some are rejected for cause and others updated. A new calculation of the statistical rate function is described and experimental ft values determined. The associated theoretical corrections needed to convert these results into Ft values are discussed, and careful attention is paid to the origin and magnitude of their uncertainties. As an exacting confirmation of the conserved vector current hypothesis, the Ft values are seen to be constant to 3 parts in 10^4. These data are also used to set new limits on any possible scalar interactions or right-hand currents. The average Ft value obtained from the survey, when combined with the muon lifetime, yields the CKM matrix element Vud = 0.9738(4); and the unitarity test on the top row of the matrix becomes |Vud|^2 + |Vus|^2 + |Vub|^2 = 0.9966(14) using the PDG's currently recommended values for Vus and Vub. We discuss the priorities for future theoretical and experimental work with the goal of making the CKM unitarity test more definitive.Comment: 64 pages, 4 postscript figure

Post partum anxiety and depression in peri-urban communities of Karachi, Pakistan: a quasi-experimental study

<p>Abstract</p> <p>Background</p> <p>Postpartum anxiety and depression is a major public health concern because of its adverse effects on the cognitive and social development of the infant. Globally postpartum depression has been widely investigated but as anxiety is a more prominent feature of postpartum depression we assessed the prevalence of anxiety and depression and their associated factors in post partum women.</p> <p>Methods</p> <p>A quasi-experimental study investigating the impact of postpartum anxiety and depression on child growth and development was conducted in two peri-urban, multiethnic, communities of Karachi, a mega city of Pakistan. A house to house questionnaire based survey was done by trained field workers; 420 consenting pregnant women were identified and data for socio-demographic, home environment and family relationship variables was collected between 36 weeks of pregnancy and within 10 days of childbirth. Mother's levels of anxiety and depression were assessed after one month, two months, six months and twelve months of childbirth; this was two step process: initially an indigenous, validated screening instrument Aga Khan University Anxiety and Depression Scale was used and diagnostic confirmation was done through a psychologist's interview based on DSM IV criteria. Women found to be anxious and depressed at least once out of four assessments were considered for the computation of overall prevalence of postpartum anxiety and depression as well as its risk factors. However, point prevalence's of postpartum anxiety and depression were also reported at each assessment time. Two sixty seven women could be followed for one year. Data was analyzed using SPSS. Chi-square test, simple and multiple logistic regression were used to see the association of different factors.</p> <p>Results</p> <p>The overall prevalence of postpartum anxiety and depression was found to be 28.8 percent. Domestic violence, difficulty in breast feeding at birth and unplanned current pregnancy were found to be significantly associated with postpartum anxiety and depression.</p> <p>Conclusion</p> <p>Domestic violence and not having the right to plan pregnancy are related to the patriarchal culture and lack of empowerment of women. The association with difficulties in breast feeding needs to be further explored in future studies</p

Real-world practice and outcomes in pilonidal surgery: pilonidal sinus treatment studying the options (PITSTOP) cohort

Background Numerous surgical approaches exist for the treatment of pilonidal disease. Current literature on treatment is of poor quality, limiting the ability to define optimal intervention. The aim of this study was to provide real-world data on current surgical practice and report patient and risk-adjusted outcomes, informing future trial design. Methods This UK-wide multicentre prospective cohort study, including patients (aged over 16 years) who had definitive treatment for symptomatic pilonidal disease, was conducted between May 2019 and March 2022. Patient and disease characteristics, and intervention details were analysed. Data on patient-reported outcomes, including pain, complications, treatment failure, wound issues, and quality of life, were gathered at various time points up to 6 months after surgery. Strategies were implemented to adjust for risk influencing different treatment choices and outcomes. Results Of the 667 participants consenting, 574 (86.1%) were followed up to the study end. Twelve interventions were observed. Broadly, 59.5% underwent major excisional surgery and 40.5% minimally invasive surgery. Complications occurred in 45.1% of the cohort. Those who had minimally invasive procedures had better quality of life and, after risk adjustment, less pain (score on day 1: mean difference 1.58, 95% c.i. 1.14 to 2.01), fewer complications (difference 17.5 (95% c.i. 9.1 to 25.9)%), more rapid return to normal activities (mean difference 25.9 (18.4 to 33.4) days) but a rate of higher treatment failure (difference 9.6 (95% c.i. 17.3 to 1.9)%). At study end, 25% reported an unhealed wound and 10% had not returned to normal activities. Conclusion The burden after surgery for pilonidal disease is high and treatment failure is common. Minimally invasive techniques may improve outcomes at the expense of a 10% higher risk of treatment failure