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A letter to the editor is presented concerning the use of neural nets to predict yarn tensile properties.

Both sleep alterations and epileptiform activity are associated with the accumulation of amyloid-β and tau pathology and are currently investigated for potential therapeutic interventions in Alzheimer's disease (AD). However, a bidirectional intertwining relation between sleep and neuronal hyperexcitability might modulate the effects of AD pathology on the corresponding associations. To investigate this, we performed multiple day simultaneous foramen ovale (FO) plus scalp EEG and polysomnography (PSG) recordings and acquired 18F-MK6240 tau PET-MR in three patients in the prodromal stage of AD and in two patients with mild and moderate dementia due to AD, respectively. As an eligibility criterion for the present study, subjects either had a history of a recent seizure (n = 2) or subclinical epileptiform activity (SEA) on a previous scalp EEG taken in a research context (n = 3). The 18F-MK6240 standard uptake value ratio (SUVR) and asymmetry index (AI) were calculated in a priori defined volumes of interest (VOIs). Linear mixed effects models were used to study associations between interictal epileptiform discharges (IEDs), PSG parameters and 18F-MK6240 SUVR. Epileptiform activity was bilateral but asymmetrically present on FO electrodes in all patients and ≥ 95% of IEDs were not visible on scalp EEG. In one patient two focal seizures were detected on FO electrodes, both without visual scalp EEG correlate. We observed lateralized periodic discharges, brief potentially ictal rhythmic discharges and lateralized rhythmic delta activity on FO electrodes in four patients. Unlike scalp EEG, intracranial electrodes showed a lateralization of epileptiform activity. Although the amount of IEDs on intracranial electrodes was not associated to the 18F-MK6240 SUVR binding in different VOIs, there was a congruent asymmetry of the 18F-MK6240 binding towards the most epileptic hemisphere for the mesial (P = 0.007) and lateral temporal cortex (P = 0.006). IEDs on intracranial electrodes were most abundant during slow wave sleep (SWS) (92/h) and N2 (81/h), followed by N1 (33/h) and least frequent during wakefulness (17/h) and REM sleep (9/h). The extent of IEDs during sleep was not reflected in the relative time in each sleep stage spent (REM% (P = 0.415), N1% (P = 0.668), N2% (P = 0.442), SWS% (P = 0.988)), and not associated with the arousal index (P = 0.317), apnea-hypopnea index (P = 0.846) or oxygen desaturation index (P = 0.746). Together, our observations suggest a multi-directional interaction between sleep, epileptiform activity and tau pathology in AD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aim: We investigated the prognostic potential of pretherapy measurement of the neutrophil/lymphocyte ratio (NLR) in patients (n = 56) with non-small-cell lung cancer deemed suitable for treatment with nivolumab., Materials & Methods: This was a multicenter, noninterventional, retrospective data analysis, involving five oncology centers., Results: Patients with prenivolumab NLR values of <5 and ≥5 had respective median overall survival (OS) values of 14.5 and 7.02 months (p = 0.0026). Patients with ≤2 and >2 metastatic sites had median OS values of 11.4 and 6.1 months, respectively (p = 0.0174). A Cox multiple regression model revealed baseline NLR ≥5 as the only variable significantly associated with decreased OS (p < 0.0447)., Conclusion: Pretreatment elevated NLR values are associated with poor outcomes in patients with recurrent metastatic non-small-cell lung cancer treated with nivolumab., Competing Interests: Financial & competing interests disclosure BL Rapoport reports personal fees from Merck and Co, grants and personal fees from BMS, grants and personal fees from Roche South Africa, personal fees from AstraZeneca, during the conduct of the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The final manuscript was supported in its entirety by the investigators. No writing assistance was utilized in the production of this manuscript., (© 2020 Rapoport BL.)

Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. The purpose of this study was to characterize the differences in cardiac electrophysiology between moxifloxacin and levofloxacin in men and women and to assess the balance of inward and outward currents through the analysis of QT subintervals. Data from 2 TQT studies were used to investigate the impact of moxifloxacin (400 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J-T peak and T peak -T end intervals. Concentration-effect analyses were performed to establish potential relationships between the ECG effects and the concentrations of the 2 fluoroquinolones. Moxifloxacin was shown to be a more potent prolonger of QT interval corrected by Fredericia (QTcF) and had a pronounced effect on J-T peak c. Levofloxacin had little effect on J-T peak c. For moxifloxacin, the concentration-effect modeling showed a greater effect for women on QTcF and J-T peak c, whereas for levofloxacin the inverse was true: women had smaller QTcF and J-T peak c effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined I Ks and I Kr inhibitory properties of moxifloxacin versus I Kr suppression only of levofloxacin. The equipotent inhibition of I Ks and I Kr appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in I Kr and I Ks balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs., (© 2019 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

Meal intake leads to a significant and prolonged increase in cardiac output to supply the splanchnic vasculature. A meal is associated with sympathetic activation of the cardiovascular system, and food ingestion is correlated with an increase in heart rate, an increase in cardiac stroke volume, and QTc interval shortening for up to 7 hours. Given the complexity of the system, one or several of many mechanisms could explain this observation. The shortening of the QTc interval was correlated with a rise of C-peptide following food ingestion, but the mechanisms by which C-peptide may be involved in the modulation of cardiac repolarization are still unknown. This shortening of the myocardial action potential caused by the ingestion of food was further investigated in the present study by measuring the QRS, J-T peak , and T peak -T end intervals in search of further clues to better understand the underlying mechanisms. A retrospective analysis was conducted based on data collected in a formal thorough QT/QTc study in which 32 subjects received a carbohydrate-rich "continental" breakfast, moxifloxacin without food, and moxifloxacin with food. We assessed the effect of food on T-wave morphology using validated algorithms for measurement of J-T peak and T peak -T end intervals. Our findings demonstrate that a standardized meal significantly shortened J-T peak for 4 hours after a meal and to a much lesser extent and shorter duration (up to 1 hour) prolonged the T peak -T end and QRS intervals. This suggests that the QTc shortening occurs mainly during phase 2 of the cardiac action potential. As there was no corresponding effect on T peak -T end beyond the first hour, we conclude that a meal does not interfere with the outward correcting potassium channels but possibly with Ca 2+ currents. An effect on mainly Ca 2+ aligns well with our understanding of physiology whereby an increase in stroke volume, as observed after a meal, is associated with changes in Ca 2+ cycling in and out of the sarcoplasmic reticulum during cardiac myocyte contraction., (© 2019, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

Purpose: Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm. Clinical HER2 status has been reported to correlate poorly with molecular subtype. The aim of this study was to investigate the correlation of clinical HER2 status with BluePrint (BP) molecular subtyping., Methods: Clinico-pathologic and genomic information was extracted from a prospectively collected central MP database containing records of 256 estrogen receptor-positive and/or progesterone receptor-positive tumors. Twenty-one tumors considered HER2 positive on immunohistochemistry or FISH were identified for this study., Results: The median age of patients was 56 years (range, 34 to 77 years), with a median tumor size of 16 mm (3 to 27 mm). Four (19%) tumors were confirmed HER2-enriched subtype, six (29%) were luminal A, and 11 (52%) were luminal B. The positive predictive values of HER2/CEP17 ratio ≥ 2 and HER2 copy number ≥ 6 were only 29% and 40%, respectively. The differences in means for HER2/CEP17 ratio were significant between BP HER2-enriched versus luminal ( P = .0249; 95% CI, 0.12 to 1.21) and MP high-risk versus low-risk tumors ( P = .0002; 95% CI, 0.40 to 1.06)., Conclusion: Of the 21 tumors considered clinically HER2 positive, only four were HER2-enriched subtype with BP, indicating an overestimation of HER2 positivity. FISH testing has a poor positive predictive value., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Ettienne J. MyburghConsulting or Advisory Role: Stellenbosch UniversityLizanne LangenhovenNo relationship to discloseKathleen A. GrantNo relationship to discloseLize Van der MerweNo relationship to discloseMaritha J. KotzeLeadership: Gknowmix Stock or Other Ownership: Genecare Molecular Genetics (dormant) (I), Gknowmix Patents, Royalties, Other Intellectual Property: Inventor (unrelated to current publication): M.J. Kotze. South African Medical Research Council. A method of diagnosing patients with cardiovascular disease or a genetic predisposition for cardiovascular disease. South African patent 2001/5419, July 2, 2001; and M.J. Kotze, S.J. van Rensburg, R. Rooney, P.D. Haug. University of Stellenbosch. In vitro method of diagnosing a demyelinating disease subtype. South African patent ZA2008/08511, September 29, 2008. (Inst)

Purpose: An estimated 5.9 million people in South Africa are infected with HIV. Because antiretroviral therapy has made infection with HIV a treatable, chronic condition, HIV-infected individuals are now surviving to middle and older age. We investigated the implications of HIV status for breast cancer in South Africa., Methods: We compared clinical and demographic characteristics of women newly diagnosed with a first primary breast cancer at Tygerberg Hospital, Cape Town, South Africa, from January 2010 to December 2011 by HIV status. We then compared HIV-positive patients with HIV-negative controls, matched 2:1 on age and ethnicity, with respect to chemotherapy regimens, toxicities, completion of systemic chemotherapy, and changes in CD4 cell count., Results: Of 586 women with breast cancer, 31 (5.3%) were HIV positive, 420 (71.7%) were HIV negative, and 135 (23%) were untested for HIV. Women with HIV were younger than other women ( P < .001). The groups did not differ in regard to stage at presentation, histologic subtype, tumor grade, nodal involvement, or hormone receptor positivity. More than 84% of patients who initiated systemic chemotherapy, regardless of HIV status, completed it without serious toxicity. Among HIV-positive patients receiving chemotherapy, the mean baseline CD4 cell count was 477 cells/µL (standard deviation, 160 cells/µL), and the mean nadir was 333 cells/µL (standard deviation, 166 cells/µL)., Conclusion: HIV-infected women were younger at breast cancer diagnosis than HIV-negative women but otherwise similar in phenotype and completion of chemotherapy. Longer term follow-up is needed to evaluate the effects of HIV, antiretroviral therapy, and chemotherapy on the survival and quality of life of patients with breast cancer., Competing Interests: Authors' disclosures of potential conflicts of interest and contributions are found at the end of this article.The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Lizanne LangenhovenNo relationship to disclosePieter BarnardtNo relationship to discloseAlfred I. NeugutStock or Other Ownership: Stemline Therapeutics Consulting or Advisory Role: Pfizer, Teva, Otsuka, United BioSource Corporation, EHE InternationalJudith S. JacobsonNo relationship to disclose