Automated gantry-type stitching system

A stitching system includes a gantry that is movable along a material support table. Mounted to the gantry are a plurality of stitching heads and bobbins. The stitching heads are individually controllable in a z-direction, and the bobbins are individually controllable in the z-direction. Each stitching head is paired with a bobbin. Each pair of stitching heads and the bobbins is controlled synchronously in the z-direction. The stitching system is well-suited for stitching preforms of aircraft wing covers and other preforms having variable thickness and compound, contoured three-dimensional surfaces

Table-driven software architecture for a stitching system

Native code for a CNC stitching machine is generated by generating a geometry model of a preform; generating tool paths from the geometry model, the tool paths including stitching instructions for making stitches; and generating additional instructions indicating thickness values. The thickness values are obtained from a lookup table. When the stitching machine runs the native code, it accesses a lookup table to determine a thread tension value corresponding to the thickness value. The stitching machine accesses another lookup table to determine a thread path geometry value corresponding to the thickness value

A phase 1 study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumors.

Background: This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly(ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours. Methods: Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide. Subsequently, the study was amended to focus on oral rucaparib (once daily, days 1–14) combined with carboplatin (day 1) in 21-day cycles. Dose-limiting toxicities (DLTs) were assessed in cycle 1 and safety in all cycles. Results: Eighty-five patients were enrolled (22 breast, 15 ovarian/peritoneal, and 48 other primary cancers), with a median of three prior therapies (range, 1–7). Neutropenia (27.1%) and thrombocytopenia (18.8%) were the most common grade greater than or equal to3 toxicities across combinations and were DLTs with the oral rucaparib/carboplatin combination. Maximum tolerated dose for the combination was 240 mg per day oral rucaparib and carboplatin area under the curve 5 mg ml−1 min−1. Oral rucaparib demonstrated dose-proportional kinetics, a long half-life (≈17 h), and good bioavailability (36%). Pharmacokinetics were unchanged by carboplatin coadministration. The rucaparib/carboplatin combination had radiologic antitumour activity, primarily in BRCA1- or BRCA2-mutated breast and ovarian/peritoneal cancers. Conclusions: Oral rucaparib can be safely combined with a clinically relevant dose of carboplatin in patients with advanced solid tumours (Trial registration ID: NCT01009190)

Reliability of sexual risk behavior interviews with psychiatric patients

Test-retest interviews examining recent sexual activity were administered to 27 severely ill psychiatric patients after stabilization. Three reports were judged to be questionable. For the I6 sexually active patients among the remaining 24, high test-retest reliability was found for number of sexual partners, frequency of episodes, and proportions of episodes involving vaginal intercourse and use of condoms. The interviews did not exacerbate psychiatric symptoms

The Ursinus Weekly, November 8, 1951

75 students, faculty give blood Friday • Pianist scheduled for local concert Thursday evening • Jones reads short stories at meeting • Another bus added for local students • Jane Gulick named news editor on Weekly staff • All-Ursinus cast stars in Philadelphia TV program • Forum speaker tells of far east situation • Freshmen start work on Booster Committee • Big Sisters to entertain Little Sisters at party • First group play planned • 35 women accept bids to five campus sororities • Dr. Rice attends Atlantic Union confab in Memphis • Y groups discuss respective topics • Final plans made for Junior Class bazaar • Kenny named frosh president • Editorials: Letters sought; Tories bring changes • Donahue describes exotic meal in Moroccan letter • Weekly drama critics see play, interview leading female star • Curtain Club boasts eventful past years • Greek sisters rush soph prospects • 3 groups produce most U.C. pep • Football fans often forget grid managers at games • Adelphi to tackle Bruins next week • Ursinus battles Bryn Mawr to 0-0 tie; Junior varsity squads also deadlock • Diplomat gridders defeat Grizzlies on muddy field • Frosh fan gives opinion on lack of Ursinus spirit • Local hockey team places eight on all-college tournament squads • Curtis squad regains loop lead in football • Fords conquer Bruin booters • Magical phenomena explained to grouphttps://digitalcommons.ursinus.edu/weekly/1526/thumbnail.jp

The Role of Travel Medicine in Managing Future Pandemics:Lessons Learned from Global Infectious Disease Outbreaks

In an increasingly interconnected world shaped by globalization, international travel plays a significant role in facilitating the spread of infectious diseases. Travel medicine plays a vital role in preventing and controlling the spread of infectious diseases. This specialized field focuses on providing pre-travel advice, administering necessary vaccinations, promoting preventive measures during travel, and offering post-travel care. Risk assessment is essential to evaluate potential hazards associated with specific destinations. Factors such as disease prevalence, healthcare infrastructure, vaccination requirements, environmental, as well as cultural influences are considered. Through this process, the risks can be effectively managed by formulating appropriate strategies. Preventive measures are crucial to minimize the transmission of infectious diseases during travel. These include compulsory vaccinations based on destination-specific requirements, recommended travel restrictions when necessary, and quarantine protocols for individuals exhibiting symptoms. Enhanced surveillance efforts combined with promotion of personal hygiene practices aid further prevention. Educating travelers about safe food handling practices also serves as an effective measure against many infections. Effective pandemic management requires collaboration among countries and international organizations. Travel medicine Professionals work alongside public health authorities to provide accurate information, vaccine administration services, and increased awareness about preventive measures. This collaborative effort facilitates timely response mechanisms ensuring global protection from emerging threats like pandemics

Evaluation of kratom opioid derivatives as potential treatment option for alcohol use disorder

Background and Purpose: Mitragyna speciosa extract and kratom alkaloids decrease alcohol consumption in mice at least in part through actions at the δ-opioid receptor (δOR). However, the most potent opioidergic kratom alkaloid, 7-hydroxymitragynine, exhibits rewarding properties and hyperlocomotion presumably due to preferred affinity for the mu opioid receptor (µOR). We hypothesized that opioidergic kratom alkaloids like paynantheine and speciogynine with reduced µOR potency could provide a starting point for developing opioids with an improved therapeutic window to treat alcohol use disorder. Experimental Approach: We characterized paynantheine, speciociliatine, and four novel kratom-derived analogs for their ability to bind and activate δOR, µOR, and κOR. Select opioids were assessed in behavioral assays in male C57BL/6N WT and δOR knockout mice. Key Results: Paynantheine (10 mg∙kg(−1), i.p.) produced aversion in a limited conditioned place preference (CPP) paradigm but did not produce CPP with additional conditioning sessions. Paynantheine did not produce robust antinociception but did block morphine-induced antinociception and hyperlocomotion. Yet, at 10 and 30 mg∙kg(−1) doses (i.p.), paynantheine did not counteract morphine CPP. 7-hydroxypaynantheine and 7-hydroxyspeciogynine displayed potency at δOR but limited µOR potency relative to 7-hydroxymitragynine in vitro, and dose-dependently decreased voluntary alcohol consumption in WT but not δOR in KO mice. 7-hydroxyspeciogynine has a maximally tolerated dose of at least 10 mg∙kg(−1) (s.c.) at which it did not produce significant CPP neither alter general locomotion nor induce noticeable seizures. Conclusion and Implications: Derivatizing kratom alkaloids with the goal of enhancing δOR potency and reducing off-target effects could provide a pathway to develop novel lead compounds to treat alcohol use disorder with an improved therapeutic window

Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda

BACKGROUND Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. INTERVENTION Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. LESSONS LEARNT Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. RECOMMENDATIONS Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries

The biased apelin receptor agonist, MM07, reverses Sugen/hypoxia-induced pulmonary arterial hypertension as effectively as the endothelin antagonist macitentan

Introduction: Pulmonary arterial hypertension (PAH) is characterised by endothelial dysfunction and pathological vascular remodelling, resulting in the occlusion of pulmonary arteries and arterioles, right ventricular hypertrophy, and eventually fatal heart failure. Targeting the apelin receptor with the novel, G protein-biased peptide agonist, MM07, is hypothesised to reverse the developed symptoms of elevated right ventricular systolic pressure and right ventricular hypertrophy. Here, the effects of MM07 were compared with the clinical standard-of-care endothelin receptor antagonist macitentan.Methods: Male Sprague-Dawley rats were randomised and treated with either normoxia/saline, or Sugen/hypoxia (SuHx) to induce an established model of PAH, before subsequent treatment with either saline, macitentan (30 mg/kg), or MM07 (10 mg/kg). Rats were then anaesthetised and catheterised for haemodynamic measurements, and tissues collected for histopathological assessment.Results: The SuHx/saline group presented with significant increases in right ventricular hypertrophy, right ventricular systolic pressure, and muscularization of pulmonary arteries compared to normoxic/saline controls. Critically, MM07 was as at least as effective as macitentan in significantly reversing detrimental structural and haemodynamic changes after 4 weeks of treatment.Discussion: These results support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease