A per-cent-level determination of the nucleon axial coupling from quantum chromodynamics.

The axial coupling of the nucleon, gA, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of gA makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome1,2: contamination of gA from excited states must be controlled in the calculations and statistical precision must be improved markedly2-10. Here we use an unconventional method 11 inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a gA value of 1.271 ± 0.013, which has a precision of about one per cent.

Design concepts for DNA-encoded library synthesis.

An approach of building block (BB) inclusivity and atom efficient library schemes deliver the quality and diversity of DNA-encoded libraries best suited for small molecule drug discovery. In this Perspective, we offer key learnings in DEL design from a decade's worth of DEL-driven screening.

Heavy Physics Contributions to Neutrinoless Double Beta Decay from QCD.

Observation of neutrinoless double beta decay, a lepton number violating process that has been proposed to clarify the nature of neutrino masses, has spawned an enormous world-wide experimental effort. Relating nuclear decay rates to high-energy, beyond the standard model (BSM) physics requires detailed knowledge of nonperturbative QCD effects. Using lattice QCD, we compute the necessary matrix elements of short-range operators, which arise due to heavy BSM mediators, that contribute to this decay via the leading order π^{-}→π^{+} exchange diagrams. Utilizing our result and taking advantage of effective field theory methods will allow for model-independent calculations of the relevant two-nucleon decay, which may then be used as input for nuclear many-body calculations of the relevant experimental decays. Contributions from short-range operators may prove to be equally important to, or even more important than, those from long-range Majorana neutrino exchange.

Deviating from IDSA treatment guidelines for non-purulent skin infections increases the risk of treatment failure in emergency department patients.

The Infectious Disease Society of America (IDSA) publishes guidelines regularly for the management of skin and soft tissue infections; however, the extent to which practice patterns follow these guidelines and if this can affect treatment failure rates is unknown. We observed the treatment failure rates from a multicentre retrospective ambulatory cohort of adult emergency department patients treated for a non-purulent skin infection. We used multivariable logistic regression to examine the role of IDSA classification and whether adherence to IDSA guidelines reduced treatment failure. A total of 759 ambulatory patients were included in the cohort with 17.4% failing treatment. Among all patients, 56.0% had received treatments matched to the IDSA guidelines with 29.1% over-treated, and 14.9% under-treated based on the guidelines. After adjustment for age, gender, infection location and medical comorbidities, patients with a moderate infection type had three times increased risk of treatment failure (adjusted risk ratio (aRR) 2.98; 95% confidence interval (CI) 1.15-7.74) and two times increased risk with a severe infection type (aRR 2.27; 95% CI 1.25-4.13) compared with mild infection types. Patients who were under-treated based on IDSA guidelines were over two times more likely to fail treatment (aRR 2.65; 95% CI 1.16-6.05) while over-treatment was not associated with treatment failure. Patients ⩾70 years of age had a 56% increased risk of treatment failure (aRR 1.56; 95% CI 1.04-2.33) compared with those <70 years. Following the IDSA guidelines for non-purulent SSTIs may reduce the treatment failure rates; however, older adults still carry an increased risk of treatment failure.

The impact of mastectomy type on the Female Sexual Function Index (FSFI), satisfaction with appearance, and the reconstructed breast's role in intimacy.

BACKGROUND: As mastectomy rates increase and overall survival for early breast cancer improves, a better understanding of the long-term consequences of mastectomy is needed. We sought to explore the correlation of specific mastectomy type with the Female Sexual Function Index (FSFI), body image satisfaction, and the reconstructed breast's role in intimacy. METHODS: This study is a secondary analysis of a cross-sectional survey including a retrospective chart review. Patients at least one year from primary surgery were invited to complete the survey between 2012 and 2014. Baseline characteristics and survey responses were compared between three mastectomy groups: total/modified radical (TMRM), skin-sparing (SSM), and nipple-sparing (NSM). All patients underwent reconstruction. RESULTS: Of 453 invited, 268 (59%) completed the survey. Sixty underwent mastectomy with reconstruction: 16 (27%) TMRM, 36 (60%) SSM, and 8 (13%) NSM. There were no significant differences in median total FSFI scores between groups, yet median FSFI scores for the NSM group indicated sexual dysfunction. After adjusting for receipt of chemotherapy and/or radiation, NSM had the lowest median desire score. There was a trend for the NSM group to be the least satisfied with postoperative appearance, but also more likely to report that the chest was "often" caressed during intimacy. However, nearly 40% of the NSM group reported that caress of the reconstructed breast was unpleasant. CONCLUSION: NSM offers patients the greatest opportunity for preservation of their native skin envelope and potentially enhanced cosmetic outcome, but our results did not demonstrate superior sexual function or body image outcomes in this group. By highlighting surgical consequences of mastectomy preoperatively, surgeons may better set realistic patient expectations regarding both aesthetic and functional outcomes after breast cancer surgery. With clearer expectations, patients will have a better opportunity for improved surgical decision-making.

Preferences for oral fluid rapid HIV self-testing among social media-using young black, Hispanic, and white men-who-have-sex-with-men (YMSM): implications for future interventions.

OBJECTIVES: We assessed preferences of social media-using young black, Hispanic and white men-who-have-sex-with-men (YMSM) for oral fluid rapid HIV self-testing, as compared to other currently available HIV testing options. We also identified aspects of the oral fluid rapid HIV self-test that might influence preferences for using this test instead of other HIV testing options and determined if consideration of HIV testing costs and the potential future availability of fingerstick rapid HIV self-testing change HIV testing preferences. STUDY DESIGN: Anonymous online survey. METHODS: HIV-uninfected YMSM across the United States recruited from multiple social media platforms completed an online survey about willingness to use, opinions about and their preferences for using oral fluid rapid HIV self-testing and five other currently available HIV testing options. In a pre/post questionnaire format design, participants first indicated their preferences for using the six HIV testing options (pre) before answering questions that asked their experience with and opinions about HIV testing. Although not revealed to participants and not apparent in the phrasing of the questions or responses, the opinion questions concerned aspects of oral fluid rapid HIV self-testing (e.g. its possible advantages/disadvantages, merits/demerits, and barriers/facilitators). Afterward, participants were queried again about their HIV testing preferences (post). After completing these questions, participants were asked to re-indicate their HIV testing preferences when considering they had to pay for HIV testing and if fingerstick blood sample rapid HIV self-testing were an additional testing option. Aspects about the oral fluid rapid HIV self-test associated with increased preference for using the test (post-assessment vs pre-assessment of opinion topics) were identified through multivariable regression models that adjusted for participant characteristics. RESULTS: Of the 1975 YMSM participants, the median age was 22 years (IQR 20-23); 19% were black, 36% Hispanic, and 45% white; and 18% previously used an oral fluid rapid HIV self-test. Although views about oral fluid rapid HIV self-testing test were favorable, few intended to use the test. Aspects about the oral fluid rapid HIV self-test associated with an increased preference for using the test were its privacy features, that it motivated getting tested more often or as soon as possible, and that it conferred feelings of more control over one's sexual health. Preferences for the oral fluid rapid HIV self-test were lower when costs were considered, yet these YMSM were much more interested in fingerstick blood sampling than oral fluid sampling rapid HIV self-testing. CONCLUSIONS: Despite the perceived advantages of the oral fluid rapid HIV self-test and favorable views about it by this population, prior use as well as future intention in using the test were low. Aspects about oral fluid rapid HIV self-testing identified as influential in this study might assist in interventions aimed to increase its use among this high HIV risk population as a means of encouraging regular HIV testing, identifying HIV-infected persons, and linking them to care. Although not yet commercially available in the United States, fingerstick rapid HIV self-testing might help motivate YMSM to be tested more than oral fluid rapid HIV self-testing.

The menstrual bleeding questionnaire: development and validation of a comprehensive patient-reported outcome instrument for heavy menstrual bleeding.

OBJECTIVE: To develop and validate a patient-reported outcome measure for women with heavy menstrual bleeding (HMB). STUDY DESIGN: Prospective cohort and cross-sectional studies. SETTING: Outpatient women's health facility. POPULATION: Women aged between 18 and 55 years with and without self-reported HMB. METHODS: Using data from patients and clinicians, we developed a patient-reported outcome measure for HMB; the Menstrual Bleeding Questionnaire (MBQ). Participants in the validation studies completed demographic and general health questionnaires and either (1) bleeding and quality of life data collected daily on handheld computers and the MBQ after 1 month or (2) the MBQ at enrolment only. A subset of women also completed the Short-form-36 (SF-36) generic quality of life questionnaire. We performed psychometric analyses of the MBQ to assess its internal consistency as well as its content and concurrent validity and ability to discriminate between women with and without HMB. MAIN OUTCOME MEASURES: Psychometric properties of the questionnaire. RESULTS: Overall, 182 women participated in the MBQ validation studies. We found that the MBQ domains were internally consistent (Cronbach's α = 0.87-0.94). There was excellent correlation between daily bleeding-related symptom data and the MBQ completed at 1 month (ρ > 0.7 for all domains). We found low to moderate correlation between the MBQ scores and SF-36 scores (ρ = -0.15 to -0.45). The MBQ clearly discriminated between women with and without HMB (mean MBQ score = 10.6 versus 30.8, P < 0.0001). CONCLUSIONS: The MBQ is a valid patient-reported outcome measure for HMB that has the potential to improve the evaluation of women with self-reported HMB in research and clinical practice.

Breast cancer survivors of different sexual orientations: which factors explain survivors' quality of life and adjustment?

BACKGROUND: Little is known about differences by sexual orientation in explanatory factors of breast cancer survivors' quality of life, anxiety, and depression. PATIENTS AND METHODS: Survivors were recruited from a cancer registry and additional survivors recruited through convenience methods. Data were collected via telephone survey from all 438 survivors, who were disease free and diagnosed with non-metastatic breast cancer an average of 5 years earlier. To explain quality of life, anxiety, and depression, we focused on sexual orientation as the primary independent factors, in addition, considering demographic, psychosocial, clinical, and functional factors as correlates. RESULTS: Sexual orientation had indirect associations with each of the outcomes, through disease-related and demographic factors as well as psychosocial and coping resources. The various explanatory models explain between 36% and 50% of the variance in outcomes and identified areas of strengths and vulnerabilities in sexual minority compared with heterosexual survivors. CONCLUSIONS: This study's findings of strengths among specific subgroups of sexual minority compared with heterosexual survivors require further explorations to identify the reasons for this finding. Most of the identified vulnerabilities among sexual minority compared with heterosexual survivors of breast cancer are amenable to change by interventions.

Immunophysiology of Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus (Mitchill), and the relationship to parasitic copepod, Dichelesthium oblongum (Abilgaard) infection.

The copepod parasite, Dichelesthium oblongum, is known to infect the Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus, within the area near New York city, USA, known as the NY Bight. The gross pathology associated with the juvenile and adult copepod stages along with the parasite's link in causing changes in sturgeon osmoregulatory capabilities has led us to investigate the host immunophysiology in relation to this host-parasite system. All the host variables, which included gill Na(+) -K(+) -ATPase activity, serum alkaline phosphatase (AP) and white blood cell differential counts, were affected in a non-linear manner by the copepod parasite. The parasites increased the host gill Na(+) -K(+) -ATPase activity and serum AP along with the percentage granulocytes while decreasing the percentage lymphocytes. A new method, developed to sample and preserve white blood cells in the field for future flow cytometry analysis, proved adequate. The effects of fish size, location and time of sampling were accounted for by the use of generalized linear models, and their effects on the host variables are discussed.

A Psychosocial Adjustment Measure for Persons With Upper Limb Amputation.

BACKGROUND: Measurement of psychosocial adjustment after upper limb amputation (ULA) could be helpful in identifying persons who may benefit from interventions, such as psychotherapy and/or support groups. However, available measures of psychosocial adjustment after limb loss are currently designed for prosthetic users only. OBJECTIVE: To create a measure of psychosocial adjustment for persons with ULA that could be completed by individuals regardless of whether a prosthesis is use. METHODOLOGY: We modified items from an existing Trinity Amputation and Prosthesis Experience Survey (TAPES) measure and generated new items pertinent to persons who did not use a prosthesis. Item content was refined through cognitive interviewing and pilot testing. A telephone survey of 727 persons with major ULA (63.6% male, mean age of 54.4) was conducted after pilot-testing. After exploratory and confirmatory factor analyses (EFA and CFA), Rasch analyses were used to evaluate response categories, item fit and differential item functioning (DIF). Item-person maps, score distributions, and person and item reliability were examined. Test-retest reliability was evaluated in a 50-person subsample. FINDINGS: EFA and CFA indicated a two-factor solution. Rasch analyses resulted in a 7-item Adjustment to Limitation subscale (CFI=0.96, TLI=0.95, RMSEA=0.128) and a 9-item Work and Independence subscale (CFI=0.935, TLI=0.913, RMSEA=0.193). Cronbach alpha and ICC were 0.82 and 0.63 for the Adjustment to Limitation subscale and 0.90 and 0.80 for the Work and Independence subscale, respectively. CONCLUSIONS: This study developed the Psychosocial Adjustment to Amputation measure, which contains two subscales: 1) Adjustment to Limitation and 2) Work and Independence. The measure has sound structural validity, good person and item reliability, and moderate to good test-retest reliability.

Parity doubling and the S parameter below the conformal window.

We describe a lattice simulation of the masses and decay constants of the lowest-lying vector and axial resonances, and the electroweak S parameter, in an SU(3) gauge theory with N(f)=2 and 6 fermions in the fundamental representation. The spectrum becomes more parity doubled and the S parameter per electroweak doublet decreases when N(f) is increased from 2 to 6, motivating study of these trends as N(f) is increased further, toward the critical value for transition from confinement to infrared conformality.

Adaptive multigrid algorithm for the lattice Wilson-Dirac operator.

We present an adaptive multigrid solver for application to the non-Hermitian Wilson-Dirac system of QCD. The key components leading to the success of our proposed algorithm are the use of an adaptive projection onto coarse grids that preserves the near null space of the system matrix together with a simplified form of the correction based on the so-called γ5-Hermitian symmetry of the Dirac operator. We demonstrate that the algorithm nearly eliminates critical slowing down in the chiral limit and that it has weak dependence on the lattice volume.

Toward TeV conformality.

We study the chiral properties of an SU(3) gauge theory with N{f} massless Dirac fermions in the fundamental representation when N{f} is increased from 2 to 6. For N{f}=2, our lattice simulations lead to a value of psi psi/F{3}, where F is the Nambu-Goldstone-boson decay constant and psi psi is the chiral condensate, which agrees with the measured QCD value. For N{f}=6, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as N{f} increases further, toward the critical value for transition from confinement to infrared conformality.

Stimulus-specific induction of phospholipid and arachidonic acid metabolism in human neutrophils.

Phospholipid remodeling resulting in arachidonic acid (AA) release and metabolism in human neutrophils stimulated by calcium ionophore A23187 has been extensively studied, while data obtained using physiologically relevant stimuli is limited. Opsonized zymosan and immune complexes induced stimulus-specific alterations in lipid metabolism that were different from those induced by A23187. [3H]AA release correlated with activation of phospholipase A2 (PLA2) but not with cellular activation as indicated by superoxide generation. The latter correlated more with calcium-dependent phospholipase C (PLC) activation and elevation of cellular diacylglycerol (DAG) levels. When cells that had been allowed to incorporate [3H]AA were stimulated with A23187, large amounts of labeled AA was released, most of which was metabolized to 5-HETE and leukotriene B4. Stimulation with immune complexes also resulted in the release of [3H]AA but this released radiolabeled AA was not metabolized. In contrast, stimulation with opsonized zymosan induced no detectable release of [3H]AA. Analysis of [3H]AA-labeled lipids in resting cells indicated that the greatest amount of label was incorporated into the phosphatidylinositol (PI) pool, followed closely by phosphatidylcholine and phosphatidylserine, while little [3H]AA was detected in the phosphatidylethanolamine pool. During stimulation with A23187, a significant decrease in labeled PI occurred and labeled free fatty acid in the pellet increased. With immune complexes, only a small decrease was seen in labeled PI while the free fatty acid in the pellets was unchanged. In contrast, opsonized zymosan decreased labeled PI, and increased labeled DAG. Phospholipase activity in homogenates from human neutrophils was also assayed. A23187 and immune complexes, but not zymosan, significantly enhanced PLA2 activity in the cell homogenates. On the other hand, PLC activity was enhanced by zymosan and immune complexes. Stimulated increases in PLC activity correlated with enhanced superoxide generation induced by the stimulus.

The 1986 lake nyos gas disaster in cameroon, west Africa.

The sudden, catastrophic release of gas from Lake Nyos on 21 August 1986 caused the deaths of at least 1700 people in the northwest area of Cameroon, West Africa. Chemical, isotopic, geologic, and medical evidence support the hypotheses that (i) the bulk of gas released was carbon dioxide that had been stored in the lake's hypolimnion, (ii) the victims exposed to the gas cloud died of carbon dioxide asphyxiation, (iii) the carbon dioxide was derived from magmatic sources, and (iv) there was no significant, direct volcanic activity involved. The limnological nature of the gas release suggests that hazardous lakes may be identified and monitored and that the danger of future incidents can be reduced.

Time course of haemoglobin mass during 21 days live high:train low simulated altitude.

The aim of this study was to determine the time course of changes in haemoglobin mass (Hb(mass)) in well-trained cyclists in response to live high:train low (LHTL). Twelve well-trained male cyclists participated in a 3-week LHTL protocol comprising 3,000 m simulated altitude for ~14 h/day. Prior to LHTL duplicate baseline measurements were made of Hb(mass), maximal oxygen consumption (VO(2max)) and serum erythropoietin (sEPO). Hb(mass) was measured weekly during LHTL and twice in the week thereafter. There was a 3.3% increase in Hb(mass) and no change in VO(2max) after LHTL. The mean Hb(mass) increased at a rate of ~1% per week and this was maintained in the week after cessation of LHTL. The sEPO concentration peaked after two nights of LHTL but there was only a trivial correlation (r = 0.04, P = 0.89) between the increase in sEPO and the increase in Hb(mass). Athletes seeking to gain erythropoietic benefits from moderate altitude need to spend >12 h/day in hypoxia.

Body mass index (BMI), postoperative appearance satisfaction, and sexual function in breast cancer survivorship.

PURPOSE: We sought to explore the correlation between BMI and postoperative sexual function, body image, and breast-specific sensuality before and after breast cancer surgery. METHODS: A cross-sectional survey of patients at least 1 year from surgery employed the Female Sexual Function Index (FSFI) and investigator-generated questions. Patients who underwent lumpectomy (L), mastectomy (M), and mastectomy with reconstruction (MR) were compared across three BMI groups: normal weight, overweight, and obese. RESULTS: Two hundred fifty-five patients underwent lumpectomy (L, n = 174), mastectomy (M, n = 22), or mastectomy with reconstruction (MR, n = 59). Median age was 57 (range 30-93) and median BMI was 28 (range 19-45). Obese and overweight women reported more appearance dissatisfaction (18.1 and 13.0%) than normal weight women (4.1%) (p = 0.01). Lower satisfaction was associated with increasing BMI within the MR group (p = 0.05). The obese group's median FSFI score met criteria for sexual dysfunction (25.90, range 11.30-33.10). More overweight women reported their chest played an important role in intimacy before and after surgery, but a postoperative decline in the importance of this role was observed in all groups. CONCLUSIONS: Greater post-treatment BMI is inversely related to postoperative appearance satisfaction, particularly in those undergoing mastectomy with reconstruction. The role of the breast in intimacy is greatest in overweight women, but decreases postoperatively in all BMI groups. IMPLICATIONS FOR CANCER SURVIVORS: Postoperative appearance satisfaction and sexual function seems to be correlated to post-treatment BMI, which highlights the need to encourage perioperative weight management for improved survivorship outcomes.

Carnitine deficiency in preterm infants: A national survey of knowledge and practices.

OBJECTIVE: Lipid supplementation improves developmental outcomes in preterm infants. Carnitine is essential for lipid metabolism; however, despite high risk for carnitine deficiency, there are no standards for carnitine supplementation in preterm infants receiving total parenteral nutrition (TPN). Our objective was to assess knowledge, beliefs and practices regarding preterm carnitine deficiency and supplementation among neonatal practitioners. METHODS: Cross-sectional electronic survey administered via a nationally representative listserv of neonatal practitioners. RESULTS: 492 respondents participated in the survey. Only 21% of respondents were aware that carnitine is secreted by the placenta. 72% believed that carnitine deficiency was common, and 60% believed deficiency could have serious consequences. Five percent routinely screened for deficiency, and 40% routinely provided carnitine supplementation. Respondents with >5 years' experience were more likely to report using carnitine supplementation (50% vs. 38%). CONCLUSIONS: Although most respondents believed that carnitine deficiency is common and could have serious consequences, few screened for deficiency and fewer than half routinely supplemented. Thus, many preterm infants remain at risk for carnitine deficiency. Further research is needed to elucidate the risks of carnitine deficiency in these vulnerable infants.

Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes.

IGF-binding protein (IGFBP)-3 is generally considered to have actions that counterbalance those of IGFs and is therefore being developed as a cancer treatment. In breast tumors, however, high levels are associated with aggressive tumors and poor prognosis. Consistent with this we have demonstrated that although IGFBP-3 and a non-IGF-binding fragment (serine phosphorylation domain peptide) reduced attachment and enhanced apoptosis of Hs578T breast cancer cells cultured on collagen or laminin, it promoted their attachment and survival on fibronectin, which is abundant in the matrix of aggressive tumors. We have now examined the factors that determine whether IGFBP-3 has positive or negative actions on breast epithelial cells. IGFBP-3 also promoted survival of Hs578T cells in the presence of an antibody to the beta1-integrin subunit or when cholesterol-stabilized complexes were disrupted. These actions were blocked by IGF-I or a MAPK inhibitor. Serine phosphorylation domain peptide had similar actions on MCF-7 cells that were again reversed on fibronectin or with disruption of cholesterol-stabilized complexes and blocked by the beta1-integrin antibody. In contrast, IGFBP-3 promoted growth and survival for nonmalignant MCF-10A cells, but these effects were again reversed on fibronectin and blocked by the beta1 antibody or a MAPK inhibitor or by disruption of cholesterol-stabilized complexes. On Hs578T cells, IGFBP-3 bound to caveolin-1 and beta1-integrins, enhancing their aggregation, the recruitment of focal adhesion kinase, and the activation of MAPK. In summary, with three breast epithelial cell lines, IGFBP-3 had positive or negative effects on growth and survival dependent upon the status of cholesterol-stabilized integrin receptor complexes.

Surgical management of soft tissue sarcoma in patients over 80 years.

AIMS: To report outcome on patients over 80years of age with soft tissue sarcoma (STS), with respect to surgical treatment, co-morbidity, complications and survival. METHODS: From a prospective database of 3400 patients with STS presenting over a 13-year period, all patients over 80years of age were identified and reviewed, with respect to tumour characteristics morbidity, mortality and outcome. RESULTS: 128 patients over 80years were treated for STS with 63 referred for treatment of primary disease, of whom 50 underwent resectional surgery. The remaining 65 patients were treated for recurrent or incompletely excised disease. Of the 50 patients treated primarily with surgery, 56% of tumours where high grade and 56% were greater than 10cm in diameter. The overall complication rate was 34%, with a 30-day mortality of 4%. Two- and 5-year survival rates were 56% and 46%, with a local recurrence rate of 22% at a mean follow-up of 22months. CONCLUSION: This patient group presented with poor prognosis tumours that were associated with poor outcomes in the medium to long term. Age need not be considered a contra-indication to radical surgery with curative intent.