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Study Objectives: The objectives of this study were to examine the relationships between sleep regularity and nonsuicidal self-injury (NSSI), including lifetime NSSI history and daily NSSI urges., Methods: Undergraduate students (N = 119; 18-26 years), approximately half of whom endorsed a lifetime history of repetitive NSSI, completed a 10-day actigraphy and ecological momentary assessment (EMA) protocol. A Sleep Regularity Index was calculated for all participants using scored epoch by epoch data to capture rapid changes in sleep schedules. Participants responded to EMA prompts assessing NSSI urge severity and negative affect three times daily over the 10-day assessment period., Results: Results indicate that individuals with a repetitive NSSI history were more likely to experience sleep irregularity than those without a history of NSSI. Findings also suggest that sleep irregularity was associated with more intense urges to engage in NSSI on a daily basis, even after accounting for average daily sleep duration, sleep timing, negative affect, and NSSI history. Neither sleep duration nor sleep timing was associated with NSSI history nor daily NSSI urge intensity., Conclusions: Findings suggest that sleep irregularity is linked with NSSI, including NSSI history and intensity of urges to engage in NSSI. The present study not only supports the growing evidence linking sleep disturbance with the risk for self-injury but also demonstrates this relationship using actigraphy and real-time assessments of NSSI urge severity. Findings highlight the importance of delineating the nuances in sleep irregularity that are proximally associated with NSSI risk and identifying targets for intervention., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Remdesivir (RDV) is a nucleotide analog prodrug with demonstrated clinical benefit in patients with coronavirus disease 2019 (COVID-19). In October 2020, the US FDA approved intravenous (IV) RDV as the first treatment for hospitalized COVID-19 patients. Furthermore, RDV has been approved or authorized for emergency use in more than 50 countries. To make RDV more convenient for non-hospitalized patients earlier in disease, alternative routes of administration are being evaluated. Here, we investigated the pharmacokinetics and efficacy of RDV administered by head dome inhalation in African green monkeys (AGM). Relative to an IV administration of RDV at 10 mg/kg, an approximately 20-fold lower dose administered by inhalation produced comparable concentrations of the pharmacologically active triphosphate in lower respiratory tract tissues. Distribution of the active triphosphate into the upper respiratory tract was also observed following inhaled RDV exposure. Inhalation RDV dosing resulted in lower systemic exposures to RDV and its metabolites as compared with IV RDV dosing. An efficacy study with repeated dosing of inhaled RDV in an AGM model of SARS-CoV-2 infection demonstrated reductions in viral replication in bronchoalveolar lavage fluid and respiratory tract tissues compared with placebo. Efficacy was observed with inhaled RDV administered once daily at a pulmonary deposited dose of 0.35 mg/kg beginning approximately 8 hours post-infection. Moreover, the efficacy of inhaled RDV was similar to that of IV RDV administered once at 10 mg/kg followed by 5 mg/kg daily in the same study. Together, these findings support further clinical development of inhalation RDV.

Critics in the media have become wary of exaggerated research claims from clinical trials and epidemiological studies. Closer to home, reviews of published studies find a high frequency of poor quality in research methods, including those used for statistical analysis. The statistical literature has long recognized that questionable research findings can occur when investigators fail to set aside their own outcome preferences as they analyse and interpret data. These preferences can be related to financial interests, a concern for patients, peer recognition, and commitment to a hypothesis. Several analyses of published papers provide evidence of an association between financial conflicts of interest and reported results. If we are to regain professional and lay confidence in research findings some changes are required. Clinical journals need to develop more competence in the review of analytic methods and provide space for thorough discussion of published papers whose results are challenged. Graduate schools need to prepare students for the conflicting interests that surround the practice of statistics. Above all, each of us must recognize our responsibility to use analytic procedures that illuminate the research issues rather than those serving special interests., (Copyright 2003 John Wiley & Sons, Ltd.)

The chemokine connective tissue-activating peptide (CTAP)-III, which belongs to the leukocyte-derived growth factor family of mediators, was previously shown to be mitogenic for fibroblasts. However, it has recently been shown that CTAP-III, released from platelets, can act like a heparanase enzyme and degrade heparan sulfate. This suggests that CTAP-III may also function as a proinflammatory mediator. We have successfully cloned CTAP-III from a lambdagt11 cDNA library of PHA-activated human CD4(+) T cells and produced recombinant CTAP-III as a fusion protein with a cellulose-binding domain moiety. This recombinant CTAP-III exhibited heparanase activity and released degradation products from metabolically labeled, naturally produced extracellular matrix. We have also developed polyclonal and monoclonal antibodies, and these antibodies against the recombinant CTAP-III detected the CTAP-III molecule in human T cells, polymorphonuclear leukocytes, and placental extracts. Thus, our study provides tools to examine further immune cell behavior in inflamed sites rich with extracellular moieties and proinflammatory mediators., (Copyright 1999 Academic Press.)

Objective: To describe the clinical course of affected and unaffected eyes in patients with idiopathic macular holes., Patients: Prospective study of patients with macular holes enrolled in the Eye Disease Case-Control Study., Main Outcome Measures: The best-corrected visual acuity at follow-up was compared with that at baseline. Changes in the macular holes, including increases in size or spontaneous regression, were assessed. The rates of development of new macular holes in fellow unaffected eyes were estimated., Results: Of the 198 patients examined at baseline, 28 (14.1%) died before reevaluation. Of those who survived, 122 (71.8%) had a follow-up examination. Approximately 34% (34.4%) of all eyes with macular holes had an increase in the size of the macular hole. Forty-five percent of eyes had a decrease in visual acuity of 2 or more lines and 27.8%, of 3 or more lines; 40.9% remained stable, with a gain or loss of fewer than 2 lines. The rate of development of a new macular hole during follow-up in fellow eyes that were unaffected at baseline was 4.3% for 3 or fewer years of follow-up, 6.5% for 4 to 5 years of follow-up, and 7.1% for 6 or more years of follow-up. Spontaneous regression of the macular hole occurred in 3 (8.6%) of 35 patients with a follow-up interval of 6 or more years, whereas no regression occurred in patients with a shorter follow-up., Conclusions: The visual acuity of 45.0% of eyes with macular holes deteriorated by 2 or more lines during follow-up. The rate of development of macular holes in unaffected fellow eyes was low.

Unlabelled: We sought to determine the potential for disposable prefilled humidifiers to become contaminated during extended patient use., Methods & Materials: We sampled the water in 55 humidifier reservoirs, which were being used by patients or which had been used by patients and then been placed on 'standby,' and had the samples cultured by a commercial clinical laboratory., Results: None of the humidifiers showed contamination after 72 hours of continuous patient use, and 33 of the 55 were used by patients for an additional 3-9 days with no contamination. Fifteen humidifiers that had been in use on patients were put in a standby mode for 30-32 days, with 5 continuing for 60-62 days, with no contamination seen., Conclusions: An automatic 72-hour change-out for prefilled humidifiers used with low-flow oxygen (less than or equal to 4 L/min) is wasteful. Our study demonstrates that the use-time of humidifiers can be safely extended to as long as 6-12 days.

The combined results from the case-control studies of Peleg, Stähelin, and Willett were found to provide no evidence of a relationship between serum retinol levels and the risk of cancer in all sites combined or of lung cancer. However, a relationship between serum retinol levels and the risk of gastrointestinal cancer was suggested.

We developed a computer model to compare the power in clinical trials that use either of two grading schemes for objectively recorded dependent variables. The example we use is an eye lens photo. The first grading system consists of side by side comparison of the before and after treatment photos; the second involves separate grading of the two photos. This modelling experience suggests that separate grading may often yield more power than side by side comparison, and offers other advantages as well. For applications in which grading error is considerably smaller in the side by side method, power may be markedly better. Most importantly, strong prejudice in favour of one or the other approach in all situations seems unwarranted.

O'Brien and Fleming (1979, Biometrics 35, 549-556) proposed a procedure for multiple testing in clinical trials for acute disease. We evaluated their procedure for chronic-disease models and found that it can be used without modification. Type I errors are unaltered and no loss of power is seen in comparison with single-sample procedures. However, average savings in sample size are less for the chronic-disease models than for the acute model. Finally, it is shown that for any specific disease model and fixed maximum number of inspections of the data, the percentage reduction in sample size can be readily predicted from the power.

Eye examinations performed on the survivors of the Framingham Heart Study Cohort showed a prevalence of senile lens changes ranging from 42% at ages 52 to 64 years to 91% at ages 75 to 85 years. The prevalence of senile macular changes increased from 35% at 52 to 64 years to 50% at 75 to 85 years. Persons affected with either condition usually had bilateral involvement. No association between the two conditions was shown.

We investigated the rates of mortality for several types of malignant melanomas for evidence that surgery accelerates metastasis. Additionally, we reanalyzed uveal melanoma survival rates from the Armed Forces Institute of Pathology. Our computations showed higher death rates in years two to five after diagnosis than in years one or six to ten. The same pattern of a peak mortality in the early years after diagnosis and lower rates six to ten years thereafter was seen in all tumor types studied. Our analysis of survival rates produced no evidence to alter the existing pattern of treatment for malignant melanoma of the uvea.