bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematics of the Ocoee Salamander (Plethodontidae: Desmognathus ocoee), with description of two new species from the southern Blue Ridge Mountains
Authors: PYRON R. ALEXANDER , BEAMER DAVID A.
Published: September 2022

The “mountain” dusky is a charismatic ecomorph of Dusky Salamander (Desmognathus): smaller (~20–50mm SVL), more terrestrial and montane woodland species, typically with round tails and extremely variable, often colorful patterns. Originally considered a single species (D. ochrophaeus), populations across the Appalachians are now divided into D. abditus, D. carolinensis, D. ochrophaeus, D. ocoee, and D. orestes, which do not form a clade but are instead scattered across the phylogeny of Desmognathus. A Coastal Plain species with a mountain dusky phenotype (D. apalachicolae) is also nested within a lineage related to D. ocoee. Within the current concept of D. ocoee, there are up to 8 genetically distinct geographic lineages which display significantly different but substantially overlapping morphologies. Recent studies have suggested that as many as six species could reasonably be delimited based on genetic data. We evaluate the strength of that evidence here and find support for five species in the D. apalachicolae + D. ocoee group. The first is D. apalachicolae in essentially its originally described form from the Coastal Plain. The second and third are D. adatsihi sp. nov. and D. balsameus sp. nov., endemic to the Great Smoky/Plott Balsam and Great Balsam Mountains, respectively. The fourth corresponds to the resurrected D. perlapsus for populations from the Alarka and Cowee Mountains in North Carolina, through the Chattahoochee River drainage to the Fall Line in the Piedmont of Georgia and Alabama. The fifth is D. ocoee, here restricted to populations in the Nantahala and Unicoi Mountains and southernmost Blue Ridge escarpment, along with previously recognized populations from the Cumberland Escarpment and Cumberland Plateau of south-central Tennessee and northeastern Alabama. This taxon concept of D. ocoee includes three deeply divergent geographic genetic segments that hybridize across two contact zones, while D. apalachicolae may be nested within some southern Blue Ridge populations of D. ocoee. The resurrected form of D. perlapsus also exhibits some admixture with the newly restricted D. ocoee. While this taxonomic arrangement is robust and stably derived from mitochondrial, morphological, and nuclear data, more sophisticated future analyses sampling additional populations and loci to estimate relationships may reach more subtle conclusions regarding the identity of some lineages within D. ocoee.
“The Deliverer Will Come”: Investigating Paul’s Adaptation of Divine Conflict Traditions in Romans
Authors: Ryan Scott C.
Published: September 2022

In recent years, scholars have shown renewed interest about the ways in which Paul’s letters utilize divine conflict traditions. In Romans 5–8 and 16:20a Paul frames the human predicament in terms of cosmic conflict and adapts divine conflict traditions, but other passages also reflect the apostle’s adaptations of these motifs. This essay will first consider the broad contours of portrayals of God as warrior in Israel’s Scriptures. Discussion will then focus on vocabulary and themes in Rom 1:18–32 and 11:25–32 to demonstrate that in these texts Paul also works with images related to divine conflict. Considering these passages from Romans alongside the divine conflict traditions of earlier voices–especially the Israelite prophets–assists in understanding Paul’s comments on wrath and judgment and assists in understanding Paul’s comments on wrath, judgment, and deliverance.
The Effects of Hepatic Impairment on the Pharmacokinetics of Doxazosin
Authors: Penenberg Darryl , Chung Menger , Walmsley Patricia , Vashi Vijay
Published: September 2022

The pharmacokinetics of doxazosin was determined in an open‐label study of 12 male volunteers with hepatic impairment (stable alcoholic cirrhosis) and 12 healthy male volunteers. Participants (fasting) received a single 2 mg doxazosin tablet, and blood samples were collected over a 120‐hour period. Safety assessments included laboratory and vital sign (blood pressure, pulse rate, and ECGs) measurements and recording of all reported adverse events. The mean peak plasma concentrations were 10.8 ng/mL and 12.3 ng/mL for the subjects with hepatic impairment and healthy subjects, respectively. The corresponding mean area under the plasma concentration‐time curve values were 246 and 172 ng•h/mL, a 43% increase in exposure in the subjects with hepatic impairment (p = 0.02). Although the apparent oral clearance was reduced by 30% in men with hepatic impairment compared with healthy subjects (p = 0.02), the elimination half‐life was not significantly changed (24 vs. 22 hours, respectively). Laboratory test results, vital signs, and the incidence of adverse events were similar for the two treatment groups. These findings indicate that the recommended dosing regimen for doxazosin is appropriate for patients with clinically mild to moderate hepatic impairment.
20th‐Century Advances in Drug Therapy in Oncology—Part II
Authors: Dutcher Janice P. , Novik Yelena , O'Boyle Kevin , Marcoullis George , Secco Christiane , Wiernik Peter H.
Published: September 2022

Ongoing research in cancer therapy has led to the development of antineoplastic agents which target specific components of the cell cycle. In Part II of this series, we discuss agents which target the mitotic mechanism by inhibiting microtubules. Although many of these agents are being shown to have multiple effects, the Vinca alkaloids and the taxanes are known as antimitotic drugs. They are among the most important anticancer agents currently available, and because of their unique mechanisms, can be combined with a wide variety of other antineoplastic agents in a spectrum of diseases. In addition, in part II, we are discussing agents that target DNA and prevent replication and thus cell growth by inhibiting the enzymes which protect DNA during replication, the topoisomerases. These drugs, too, have unique mechanisms of action and have become major components of combination regimens. The topoisomerase I inhibitors are new drugs derived from an older parent drug, and their full possibilities are still being explored.
Autogenic‐Feedback Training Exercise Is Superior to Promethazine for Control of Motion Sickness Symptoms
Authors: Cowings Patricia S. , Toscano William B.
Published: September 2022

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (IM) of promethazine, a physiological training method (autogenic‐feedback training exercise [AFTE]), and a no‐treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating‐chair motion sickness test. The motion sickness test procedures and the 7‐day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30‐minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no‐treatment control subjects were only given the four rotating‐chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.
Multiple‐Dose Pharmacokinetics of Telmisartan and of Hydrochlorothiazide following Concurrent Administration in Healthy Subjects
Authors: Yong Chan‐Loi , Dias Virgil C. , Stangier Joachim
Published: September 2022

This open‐label, crossover study had two objectives: to compare the steady‐state pharmacokinetics of high‐dose telmisartan with and without coadministered high‐dose hydrochlorothiazide and to compare the steady‐state pharmacokinetics of hydrochlorothiazide with and without coadministered telmisartan. A total of 13 healthy males and females of nonchildbearing potential received the following oral, once‐daily medications, each for 7 days: telmisartan 160 mg, hydrochlorothiazide 25 mg, and telmisartan 160 mg plus hydrochlorothiazide 25 mg. Between medication periods, there was a 14‐day washout. Blood was collected at intervals over 48 and 84 hours, respectively, at the end of the 7‐day dosing period for the determination of plasma telmisartan and hydrochlorothiazide concentrations by high‐performance liquid chromatography. Predose blood samples were also collected on days 1, 6, and 7. Tolerability of single‐agent and combination medication was monitored. For hydrochlorothiazide and telmisartan, given alone or in combination, there were no appreciable differences in trough plasma concentrations between days 6, 7, and 8; thus, at day 7, both agents had achieved steady state. Mean values of the primary end points (Cmax and AUC0–24) and secondary end points (Cmin and t1/2) for both telmisartan and hyrochlorothiazide were unaffected when administered simultaneously. Moreover, concurrent telmisartan had no effect on urinary excretion of hydrochlorothiazide. Transient lightheadedness, associated with postural hypotension, was the most common adverse event. The absence of any significant effects on the pharmacokinetics of either hydrochlorothiazide or telmisartan shows that no dose adjustment is required if the two agents are given concurrently for the management of hypertension.
Steady‐State Pharmacodynamics and Pharmacokinetics of Warfarin in the Presence and Absence of Telmisartan in Healthy Male Volunteers
Authors: Stangier Joachim , Su Chung‐An P. F. , Hendriks Maarten G. C. , van Lier Jan J. , Sollie Frans A. E. , Oosterhuis Berend , Jonkman Jan H. G.
Published: September 2022

The effects of multiple‐dose telmisartan on the steady‐state pharmacodynamics and pharmacokinetics of warfarin were assessed in 12 healthy young males in an open‐label, single‐period study conducted over 30 days. Subjects received loading doses of oral once‐daily warfarin on days 1 to 5, which were individually adjusted at days 6 and/or 9 to attain stable predose prothrombin time values (INRpre) of between 1.2 and 1.8 by the end of medication phase 1 (day 14). From days 15 to 24 (medication phase 2), subjects received oral once‐daily telmisartan 120 mg in addition to individualized oral doses of once‐daily warfarin. On days 25 to 31 (medication phase 3), oral once‐daily warfarin was again administered alone at individualized doses. Under steady‐state conditions, INRpre remained unchanged during medication phases 1, 2, and 3. The difference between phases 1 and 3 was −0.04 (95% confidence interval [CI]: −0.7 to 0.10) and between phases 2 and 1 was 0.03 (95% CI: −0.11 to 0.10). Mean trough plasma warfarin concentrations (Cpre) were stable during medication with warfarin alone but showed a small, although statistically significant, decrease during the combined‐medication phase. The point estimate of the ratio of phase 2/phase 1 was 0.89 (95% CI: 0.84 to 0.95). The decrease in Cpre did not result in decreased anticoagulation. This suggests that the extent of pharmacokinetic interaction between telmisartan and warfarin is limited, and since telmisartan had no effect on INRpre and the concomitant medication was well tolerated, there is no evidence for a clinically relevant interaction between telmisartan and warfarin.
Pharmacokinetics and Safety of Intravenous and Oral Telmisartan 20 mg and 120 mg in Subjects with Hepatic Impairment Compared with Healthy Volunteers
Authors: Stangier Joachim , Su Chung‐An P. F. , Schöndorfer G. , Roth Willy
Published: September 2022

The pharmacokinetics and safety of telmisartan were assessed in subjects with hepatic impairment in a single‐center, open‐label study. Single oral doses of telmisartan 20 mg and 120 mg, separated by a washout period of 14 days, were given to 12 hepatically impaired subjects and 12 healthy subjects. In 5 hepatically impaired subjects who received both oral doses, a single IV infusion of telmisartan 120 mg was later administered. After oral dosing, the pharmacokinetic profile of telmisartan was characterized by rapid absorption and disposition kinetics and a slow terminal elimination phase with mean half‐lives of 27 to 42 hours. The maximum plasma concentration and area under the telmisartan plasma concentration‐time curve (AUC0‐∞) increased in hepatically impaired subjects compared with healthy volunteers 6.4‐fold and 2.7‐fold, respectively, for telmisartan 20 mg and 3.2‐fold and 3.1‐fold, respectively, for telmisartan 120 mg. Maximum plasma concentrations and AUC0‐∞ after IV infusion were markedly elevated compared with values obtained from other studies conducted in healthy volunteers. Hepatic impairment resulted in an apparent increase in the absolute bioavailability of telmisartan, and total clearance following oral and IV administration was significantly reduced compared with healthy volunteers. Plasma protein binding of telmisartan was ≥ 99.5% in hepatically impaired and healthy subjects and was not changed when compared to healthy subjects. Oral and IV telmisartan were well tolerated in both the hepatically impaired and the healthy; headache was the most common potentially telmisartan‐related adverse event. Changes in vital signs and clinical laboratory parameters were transient and of no clinical relevance. The good tolerability of telmisartan in hepatically impaired patients demonstrated in this study, the proven sustained blood pressure control in hypertensive patients, and the increased exposure in patients with hepatic dysfunction suggest that effective treatment of hypertensive patients with impaired hepatic function would be achieved even with the lowest dose of telmisartan available. The increased bioavailability of telmisartan suggests that lower doses of telmisartan should be considered when the drug is administered to patients with hepatic impairment.
Dose Response and Safety of Telmisartan in Patients with Mild to Moderate Hypertension
Authors: Smith David H. G. , Matzek Kandace M. , Kempthorne‐Rawson Joan
Published: September 2022

This randomized, double‐blind, double‐dummy, placebo‐controlled, parallel‐group study evaluated the dose‐response relationship of telmisartan in 207 patients with mild to moderate hypertension (diastolic blood pressure [DBP] 100 to 114 mmHg). After a 28‐day placebo run‐in period, patients were randomized to 28 days of once‐daily, double‐blind, double‐dummy treatment with telmisartan 40, 80, or 120 mg; enalapril 20 mg; or placebo. Blood pressure (BP) was manually recorded for 12 hours after the first dose and after 24 hours at baseline (Day 0), Day 1, and Day 28 of double‐blind treatment. Pharmacokinetic and pharmacodynamic parameters were assessed from telmisartan plasma concentrations. All doses of telmisartan and enalapril significantly reduced BP compared with placebo (p ≤ 0.01). Mean ± SE reductions in supine DBP after 28 days of treatment ranged between 7.9 ± 1.3 mmHg and 9.8 ± 1.3 mmHg in the telmisartan groups, 9.6 ± 1.3 mmHg with enalapril, and 1.5 ± 1.3 mmHg with placebo. Mean ± SE reductions in supine systolic blood pressure (SBP) were between 10.0 ± 2.2 mmHg and 15.5 ± 2.2 mmHg with telmisartan versus 10.2 ± 2.1 mmHg with enalapril; placebo increased supine SBP by 3.5 ± 2.1 mmHg. The BP reductions after 4 weeks of treatment with telmisartan were no different from those achieved with enalapril. No significant linear trend in BP reduction was evident among telmisartan doses. Reductions in SBP and DBP were maintained over the 24‐hour period at Day 28. Treatment did not affect supine heart rate. Trough/peak DBP ratios were ≥ 85% for all telmisartan doses versus 65% for enalapril. High interpatient variability in telmisartan plasma concentrations was observed. For example, mean ± SD values for Cmax were 159 ± 104 ng/mL for telmisartan 40 mg, 693 ± 606 ng/mL for telmisartan 80 mg, and 1635 ± 1406 ng/mL for telmisartan 120 mg. Plasma concentration‐effect analyses indicated that the antihypertensive effects of telmisartan 40, 80, and 120 mg are at the plateau region of the concentration‐response curve. All active treatments were well tolerated, with tolerability profiles similar to placebo, and telmisartan did not produce any clinically relevant first‐dose effects. These data confirm the antihypertensive efficacy and placebo‐like tolerability of telmisartan.
Percutaneous Absorption and Pharmacokinetics of Eflornithine HC®l 13.9% Cream in Women with Unwanted Facial Hair
Authors: Malhotra Bimal , Noveck Robert , Behr Douglas , Palmisano Maria
Published: September 2022

This article reports the results of an open‐label, multiple‐dose study to determine percutaneous absorption and pharmacokinetics of eflornithine following topical treatment with eflornithine HC®l 13.9% cream (Vaniqa™). Ten women with excessive facial hair were treated with two 0.5 g single doses of [14C]‐labeled eflornithine HC®l 13.9% (w/w) cream (periods A and C) separated by twice‐daily application of 0.5 g unlabeled eflornithine HC113.9% cream for 7 days (period B). Analysis of radioactivity excreted in urine and feces indicated that percutaneous absorption was minimal. Comparison with urinary excretion of eflornithine in period A suggested that most of absorbed eflornithine was excreted in urine without being metabolized. Radioactivity was not detectable in blood or plasma, but eflornithine concentrations were measurable, with peak concentrations of 4.96 ng/ml in period A and 10.44 ng/ml in period C. Eflornithine was eliminated from plasma with a mean terminal half‐life of 11 hours (first application) and 8 hours (final application). Trough plasma concentrations reached steady state (4.61‐5.50 ng/ml) after 4 days of twice‐daily topical treatment, and multiple dosing had no apparent effect on disposition kinetics. The low degree of percutaneous absorption and low systemic exposure to eflornithine offer a favorable clinical safety profile of eflornithine HC®l 13.9% cream.
Coriolus versicolor: A Medicinal Mushroom with Promising Immunotherapeutic Values
Authors: Chu Kevin K. W. , Ho Susan S. S. , Chow Albert H. L.
Published: September 2022

Coriolus versicolor(CV) is a medicinal mushroom widely prescribed for the prophylaxis and treatment of cancer and infection in China. In recent years, it has been extensively demonstrated both preclinically and clinically that aqueous extracts obtained from CV display a wide array of biological activities, including stimulatory effects on different immune cells and inhibition of cancer growth. The growing popularity of aqueous CV extracts as an adjunct medical modality to conventional cancer therapies has generated substantial commercial interest in developing these extracts into consistent and efficacious oral proprietary products. While very limited information is available on the physical chemical, and pharmacodynamic properties of the active principles present in these extracts, there has been sufficient scientific evidence to support the feasibility of developing at least some of these constituents into an evidence‐based immunodulatory agent. In this article, the background, traditional usage, pharmacological activities, clinical effects, adverse reactions, active constituents, and regulatory aspects of CV are reviewed. Presented also in this review are the current uses and administration, potential drug interactions, and contraindication of aqueous extracts prepared from CV.
Lipid and Lipoprotein Responses to Oral Combined Hormone Replacement Therapy in Normolipemic Obese Women with Controlled Type 2 Diabetes Mellitus
Authors: Lilley Sandra H. , Spivey J. Michael , Vadlamudi Satyaprasad , Otvos James , Cummings Doyle M. , Barakat Hisham
Published: September 2022

This study investigated the effects of oral combined hormone replacement therapy (OCHRT) on lipid concentrations and subpopulation distribution of lipoproteins in nine postmenopausal women with type 2 diabetes mellitus and moderate glycemic control. After 16 weeks of continuous daily therapy of conjugated estrogens 0.625 mg and medroxyprogesterone 2.5 mg, the mean concentration of high‐density lipoprotein (HDL) cholesterol showed a statistically significant increase of 16.7%, predominantly in the HDL2 subfraction. No statistically significant changes in mean concentrations of total cholesterol, low‐density lipoprotein (LDL) cholesterol, triglycerides, very low‐density lipoprotein (VLDL) triglycerides, apolipoprotein A1, or apolipoprotein B were evident. Likewise, no changes were found in the average diameter of VLDL, LDL, or HDL particles; triglyceride concentrations of VLDL subfractions; cholesterol concentrations of LDL subfractions; or chemical composition of plasma LDL. These findings lend further support to the use of OCHRT in postmenopausal women with diabetes to decrease their risk for coronary artery disease.
Are New Asthma Therapies Needed?
Authors: O'Byrne Paul M.
Published: September 2022

For many years, effective therapy for the management of asthma has been available. Issues of adverse side effects and questionable patient compliance with current therapies have been seen as deterrents for proven beneficial agents such as the anti‐inflammatory corticosteroids and the bronchodilating β2‐agonists. As effective as available agents are, the goal of consistent efficacy and ease of use has fueled research into new therapies that are either easier to use or have a more favorable side effect profile.
Pharmacokinetics of an Oral Once‐a‐Day Controlled‐Release Oxybutynin Formulation Compared with Immediate‐Release Oxybutynin
Authors: Gupta Suneel K. , Sathyan Gayatri
Published: September 2022

Oxybutynin is used for the treatment of urge urinary incontinence. In this randomized, open‐label, two‐way crossover, multiple‐dose study, the pharmacokinetics of a once‐daily, controlled‐release formulation, OROS® oxybutynin chloride, was compared with that of immediate‐release (IR) oxybutynin (Ditropan®). Thirteen healthy female volunteers received three 5 mg OROS® oxybutynin chloride tablets once daily for 4 days or IR oxybutynin 5 mg administered every 8 hours for 4 days. On day 1, with OROS® oxybutynin chloride, mean plasma concentrations rose slowly over approximately 6 hours following dosing (mean Cmax 4.2 ng/mL) and remained fairly constant over the 24‐hour dosing interval, whereas with IR oxybutynin, mean plasma concentrations rose rapidly within the first hour after dosing (mean Cmax 12.0 ng/mL), then declined. The mean oxybutynin degree of fluctuation was much lower for OROS® oxybutynin chloride (78%) than for IR oxybutynin (371%). For both formulations, the plasma concentration‐time profiles for the metabolite N‐desethyloxybutynin paralleled those of oxybutynin but at higher concentrations. Steady‐state oxybutynin concentrations were achieved by day 3 for both formulations. Mean area under the concentration‐time curve (AUC) values for both oxybutynin and its metabolite were similar between day 1 and day 4 for each treatment, suggesting time‐invariant pharmacokinetics. With OROS® oxybutynin chloride, mean relative bioavailability was higher (153%) for oxybutynin and lower (69%) for N‐desethyloxybutynin compared with IR oxybutynin. This increased bioavailability may be due to reduced first‐pass metabolism; within 3 to 5 hours after dosing, OROS® systems are thought to reach the colon, where cytochrome P450‐mediated oxidation (oxybutynin's primary metabolic pathway) may be less extensive than in the small intestine. Fewer subjects reported any adverse event with OROS® oxybutynin chloride than with IR oxybutynin (including dry mouth, oxybutynin's most frequently reported anticholinergic adverse effect).
Effect of Montelukast on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers
Authors: van Hecken Anne , Depré Marleen , Verbesselt René , Wynants Kathleen , de Lepeleire Inge , Arnout Jef , Wong Peggy H. , Freeman Amanda , Holland Sherry , Gertz Barry , de Schepper Paul J.
Published: September 2022

Montelukast, a cysteinyl leukotriene receptor antagonist, is being developed for the treatment of asthma and related diseases. This study was designed to evaluate whether montelukast at clinically used dosage levels would interfere with the anticoagulant effect of warfarin. In a two‐period, double‐blind, randomized crossover study, 12 healthy male subjects received a single oral dose of 30 mg warfarin on the 7th day of a 12‐day treatment with montelukast, 10 mg daily by mouth, or a placebo. Montelukast had no significant effect on the area under the plasma concentration‐time curves and peak plasma concentrations of either R‐ or S‐warfarin. However, slight but statistically significant decreases in time to peak concentration of both warfarin enantiomers and in elimination half‐life of the less potent R‐warfarin were observed in the presence of montelukast. These changes were not considered as clinically relevant. Montelukast had no significant effect on the anticoagulant effect of warfarin, as assessed by the international normalized ratio (INR) for prothrombin time (AUC0–144 and INR maximum). The results of this study suggest that a clinically important interaction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.
Erythromycin Coadministration Increases Plasma Atorvastatin Concentrations
Authors: Siedlik Paul H. , Olson Stephen C. , Yang Bing‐Bing , Stern Ralph H.
Published: September 2022

The effect of erythromycin on the pharmacokinetics of atorvastatin, an inhibitor of HMG‐CoA reductase, was investigated in 12 healthy volunteers. Each subject received a single 10 mg dose of atorvastatin on two separate occasions, separated by 2 weeks. Erythromycin (500 mg qid) was given from 7 days before through 4 days after the second atorvastatin dose. Atorvastatin concentrations were determined by an enzyme inhibition assay, which measured both atorvastatin and active metabolites. When erythromycin was coadministered with atorvastatin, mean Cmax and AUC(0‐∞) increased by 37.7% and 32.5%, respectively. Mean terminal half‐life was similar following each atorvastatin dose. Possible mechanisms for this interaction include erythromycin inhibition of first‐pass conversion of atorvastatin to inactive metabolites and erythromycin inhibition of P‐glycoprotein‐mediated intestinal or biliary secretion.
States of Diffusion: Ideology, Text, Voice, and Sound in Cold War Chinas
Authors: Lekner Dayton
Published: September 2022

From 1953 to 1991, speaker installations on the coasts of the People’s Republic of China (PRC) and Taiwan sent audio signals back and forth between the two Cold War foes. This opposed amplification and diffusion of sound continued for nearly four decades, employed thousands of “callers,” technicians, station managers, scriptwriters, and other staff, and was heard by successive generations of troops and civilians on both sides. Previous research on the use of sound for mobilization and subjectification in China during this era has focused on the authoritarian, revolutionary, or even totalitarian nature of sonic statecraft. This article, drawing on state archives, memoirs, and interviews, compares the goals, infrastructure, and voices of the two sides to suggest a broader and more transnational framework for understanding acts of sonic propaganda and control, representative not of “communist” or “free” China, but as a diffusion of the state voice into acts of listening between states. It also explores how the opposed initiatives of both sides interacted and influenced each other over years of call and response. Finally, it examines the civilian response to the broadcasts, revealing plural modes of listening, and of apprehending both oneself and one’s enemy. I offer the metaphor of “diffusion” not only to describe the process by which states and individuals positioned themselves through the transmission and reception of sonic impulses, but as a way to do social history that focuses on the multiple receptions and reverberations of an event.
Nonintubated versus intubated thoracoscopic bullectomy for primary spontaneous pneumothorax: A multicenter propensity-matched analysis
Authors: Elkhouly Ahmed G , Karamustafaoglu Yekta Altemur , Galvez Carlos , Rao Madhuri , Lerut Philip , Grimonprez Annelies , Akar Firas Abu , Peer Michael , Bedetti Benedetta , Tosi Davide , Turna Akif , Elkahwagy Mohamed , Pompeo Eugenio
Published: September 2022

Background

We aimed at comparing in a multicenter propensity-matched analysis, results of nonintubated versus intubated video-assisted thoracic surgery (VATS) bullectomy/blebectomy for primary spontaneous pneumothorax (PSP).

Methods

Eleven Institutions participated in the study. A total of 208 patients underwent VATS bullectomy by intubated (IVATS) (N = 138) or nonintubated (NIVATS) (N = 70) anesthesia during 60 months. After propensity matching, 70 pairs of patients were compared. Anesthesia in NIVATS included intercostal (N = 61), paravertebral (N = 5) or thoracic epidural (N = 4) block and sedation with (N = 24) or without (N = 46) laryngeal mask under spontaneous ventilation. In the IVATS group, all patients underwent double-lumen-intubation and mechanical ventilation. Primary outcomes were morbidity and recurrence rates.

Results

There was no difference in age (26.7 ± 8 vs 27.4 ± 9 years), body mass index (19.7 ± 2.6 vs 20.6 ± 2.5), and American Society of Anesthesiology score (2 vs 2). Main results show no difference both in morbidity (11.4% vs 12.8%; p = 0.79) and recurrence free rates (92.3% vs 91.4%; p = 0.49) between NIVATS and IVATS, respectively, whereas a difference favoring the NIVATS group was found in anesthesia time ( p < 0.0001) and operative time ( p < 0.0001), drainage time ( p = 0.001), and hospital stay ( p < 0.0001). There was no conversion to thoracotomy and no hospital mortality. One patient in the NIVATS group needed reoperation due to chest wall bleeding.

Conclusion

Results of this multicenter propensity-matched study have shown no intergroup difference in morbidity and recurrence rates whereas shorter operation room time and hospital stay favored the NIVATS group, suggesting a potential increase in the role of NIVATS in surgical management of PSP. Further prospective studies are warranted.
Instructor experiences with online guitar lessons during the Covid-19 pandemic in Turkey
Authors: Ayyıldız Enes Bahadır , Zahal Onur
Published: September 2022

This study aims to analyze the distance guitar education provided by universities during the pandemic process based on the opinions of guitar educators. Twenty-six guitar instructors (academicians) who taught guitar in 24 universities participated in the study, and the data were collected through semi-structured interviews. Findings were interpreted under five categories, which were technical resources, functionality, motivation, guitar studies, and evaluation. It was found that technical problems, for example, audio delays, disconnection, and freezing were encountered. Although technical issues on the guitar can be overcome to a certain extent, it was reported that works such as musicality, and nuance were not reflected in the course. It was also emphasized that the technological possibilities are insufficient in reflecting the depths of the sound coming out of the guitar, and individual instrument guitar lessons must not be considered separately from face-to-face education. It was concluded that distance education leaves out the emotional aspects of music, and distance education can continue to support face-to-face education in the future.
Disquieting ambivalence of mega-infrastructures: Kenya’s Standard Gauge Railway as spectacle and ruination
Authors: Lesutis Gediminas
Published: September 2022

Putting research on the socio-political effects of Kenya’s new Standard Gauge Railway in conversation with geographically and anthropologically grounded scholarship on infrastructure, the article analyses how megaprojects, in spite of state spectacles of infrastructure-qua-development, are embroiled in multiple modalities of ruination. It specifically highlights how mega-infrastructures disrupt ecologies of social reproduction: the new railway disorders people’s mobility patterns and their access to essential infrastructures, as well as decouples their labour from transport systems and informal road economies central to self-sustainment. The article conceptualises these intersections between infrastructure’s spectacle and ruination as disquieting ambivalence of infrastructure. Shifting from spectacle to ruination – rather than oscillating between the two – this ambivalence is not one of uncertainty, malleability, or open-ended futures that are analysed in recent strands of critical scholarship on infrastructure, in which material devastation is often bracketed due to this literature’s predominant focus on multiple temporalities of infrastructure as heterogeneous possibilities of reconfiguration. The article, instead, shows that this ambivalence of infrastructure is disquieting – fraught with precarity, struggle, and despair, as the lives of those in shadows of mega-infrastructures need to be rebuilt within the ruins of the here and now, and of infrastructure’s spectacle.
A walking programme for adults living in the community after hip fracture: A feasibility randomized controlled trial
Authors: Taylor Nicholas F , Shields Nora , Thompson Anne L , O’Halloran Paul D , Harding Katherine E , Dennett Amy M , Hau Raphael , Peiris Casey L
Published: September 2022

Objective

To test the feasibility of a walking programme for community-dwelling adults recovering from hip fracture.

Design

A randomized controlled trial with embedded qualitative analysis.

Setting

Community.

Participants

Aged at least 60 years and living in the community after hip fracture.

Interventions

In addition to standard care, the experimental group received weekly home-based physiotherapy for 12 weeks to facilitate 100 minutes/week of moderate-intensity walking.

Main outcome measures

Feasibility domains of demand, acceptability, implementation, practicality and limited efficacy.

Results

Of 158 potentially eligible, 38 participated (23 women, mean age 80 years, SD 9). The recruitment rate of 24% indicated low demand. Participants considered the walking programme highly acceptable. The programme was implemented as intended; the experimental group received a mean of 11 (SD 1) consultations and averaged more than 100 min of walking per week. The programme was practical with no serious adverse events and no between-group difference in risk of falling or hospital readmissions. Demonstrating evidence of efficacy, there were moderate standardized mean differences for physical activity favouring the experimental group, who increased daily moderate-intensity physical activity compared to the control group (MD 8 min, 95% CI 2–13). There were no between-group differences in mobility, walking confidence or quality of life.

Conclusion

A walking programme for community-dwelling older adults after hip fracture was acceptable, could be implemented as intended and was practical and demonstrated preliminary evidence of efficacy in increasing physical activity. However, low demand would threaten the feasibility of such a programme.
Quantification of the purinergic P2X7 receptor with [11C]SMW139 improves through correction for brain-penetrating radiometabolites
Authors: Brumberg Joachim , Aarnio Richard , Forsberg Anton , Marjamäki Päivi , Kerstens Vera , Moein Mohammad M , Nag Sangram , Wahlroos Saara , Kassiou Michael , Windhorst Albert D , Halldin Christer , Haaparanta-Solin Merja , Fazio Patrik , Oikonen Vesa , Rinne Juha O , Varrone Andrea
Published: September 2022

The membrane-based purinergic 7 receptor (P2X7R) is expressed on activated microglia and the target of the radioligand [11C]SMW139 for in vivo assessment of neuroinflammation. This study investigated the contribution of radiolabelled metabolites which potentially affect its quantification. Ex vivo high-performance liquid chromatography with a radio detector (radioHPLC) was used to evaluate the parent and radiometabolite fractions of [11C]SMW139 in the brain and plasma of eleven mice. Twelve healthy humans underwent 90-min [11C]SMW139 brain PET with arterial blood sampling and radiometabolite analysis. The volume of distribution was estimated by using one- and two- tissue compartment (TCM) modeling with single ( VT) and dual ( VTp) input functions. RadioHPLC showed three major groups of radiometabolite peaks with increasing concentrations in the plasma of all mice and humans. Two radiometabolite peaks were also visible in mice brain homogenates and therefore considered for dual input modeling in humans. 2TCM with single input function provided VT estimates with a wide range (0.10–10.74) and high coefficient of variation (COV: 159.9%), whereas dual input function model showed a narrow range of VTp estimates (0.04–0.24; COV: 33.3%). In conclusion, compartment modeling with correction for brain-penetrant radiometabolites improves the in vivo quantification of [11C]SMW139 binding to P2X7R in the human brain.
EU integration and the geographies of economic activity: 1985–2019
Authors: Cutrini Eleonora , Gardiner Ben , Martin Ron
Published: September 2022

One of the central predictions of the new economic geography (NEG) is that the removal of trade barriers and other such frictions should lead to the geographical concentration and specialisation of economic activity, both between and within nations. This prediction has been used to argue that as the European Union becomes more integrated, economic activity would become more regionally concentrated and specialised. Using relative entropy measures applied to a new regional data set for the period of 1985–2019, this paper finds that between 1985 and 2000 localisation and specialisation between European countries increased to some extent but with a widespread fall in specialisation and concentration within countries. After 2000, and particularly after 2007 and the Global financial Crisis, the spatial distribution of economic activities in Europe appears to have become more complex, with some degree of concentration, agglomeration and specialisation both across and within countries. Overall, however, we find little long-run support for the NEG prediction.
Predicting Hospitalization among Medicaid Home- and Community-Based Services Users Using Machine Learning Methods
Authors: Jung Daniel , Pollack Harold A. , Konetzka R Tamara
Published: September 2022

We compare multiple machine learning algorithms and develop models to predict future hospitalization among Home- and Community-Based Services (HCBS) Users. Furthermore, we calculate feature importance, the score of input variables based on their importance to predict the outcome, to identify the most relevant variables to predict hospitalization. We use the 2012 national Medicaid Analytic eXtract data and Medicare Provider Analysis and Review data. Predicting any hospitalization, Random Forest appears to be the most robust approach, though XGBoost achieved similar predictive performance. While the importance of features varies by algorithm, chronic conditions, previous hospitalizations, as well as use of services for ambulance, personal care, and durable medical equipment were generally found to be important predictors of hospitalization. Utilizing prediction models to identify those who are prone to hospitalization could be useful in developing early interventions to improve outcomes among HCBS users.
Shipwrecks: Their impact on the behavioural patterns of sailors and on littoral societies during the age of sail in the western Indian Ocean, circa 800–1600
Authors: Chowdhary Mir Kamruzzaman
Published: September 2022

This article begins by investigating the construction techniques of medieval Indian ships to explore the extent to which the building methods were responsible for shipwrecks. Then, the article attends to the impacts of a shipwreck on the minds or behaviour of sailors. A link is drawn between various superstitious beliefs and certain irrational behaviour among sailors in the Indian Ocean and shipwrecks. The dreaded nature of a voyage would often create panic among sailors, which led them to various superstitious beliefs. However, a voyage would also attract many with the promise of adventure. The article also discusses how the atmosphere in the ship played the role of a catalyst in shaping the behaviour of the mariners. Finally, the article explores the ramifications of shipwrecks in littoral societies across the western Indian Ocean. During the medieval period, merchants from different regions and countries whose livelihood depended on the maritime trade settled in port towns. Moreover, littoral people relied on the supply of products from across the oceans for their livelihoods. Therefore, the smooth conduct of shipping was necessary for these coastal people. This article examines how a shipwreck would impact sectors of the littoral society in general and sailors in particular. Although the paucity of sources sets limits on the extent to which these aspects can be reconstructed, a number of contemporary traveller accounts shed light on the situation.
Agranulocytosis Associated With Use of Sulfamethoxazole/Trimethoprim in a Healthy Adult
Authors: Bunch David , Brands Carolyn , Langworthy Diana R.
Published: September 2022

Purpose: A case of sulfamethoxazole/trimethoprim-induced agranulocytosis is reported. Summary: A 53-year-old healthy male presented to the emergency room with a fever of 102.7°F and was found to have a white blood cell (WBC) count of 0.6 × 103 cells/μL with an absolute neutrophil count (ANC) of 0.0 x 103 cells/μL. He had recently completed a 10-day course of sulfamethoxazole/trimethoprim for left lower extremity cellulitis. During admission, a bone marrow biopsy was performed which was not concerning for malignancy and no cause for the agranulocytosis other than the sulfamethoxazole/trimethoprim was identified. The agranulocytosis resolved after 6 days of hospitalization with a WBC count of 8.9 × 103 cells/μL and an ANC of 4.1 x 103cells/μL on the day of discharge. Conclusion: A 53-year-old male developed agranulocytosis after 10 days of sulfamethoxazole/trimethoprim therapy for the treatment of a skin and soft tissue infection. His neutropenia resolved after sulfamethoxazole/trimethoprim discontinuation.
Trafficking, Rape, or Deceptive Sex? A Historical Examination of Procurement Offences in England
Authors: Lammasniemi Laura
Published: September 2022

This article examines the origins of procurement offences and their historical development in England. Procurement offences were created in 1885 to tackle so-called white slavery, as trafficking in women was then sensationally called. Through an analysis of a series of lower-level and appeal cases heard between the years of 1885 and 1925 and their social context, this article dispels myths about procurement for prostitution as an international, organised crime, showing instead how it was localised and poverty driven. The article also shows how procurement transformed from a narrowly defined trafficking-related offence into a broadly applied sexual offence. It came to be used as a ‘catch-all’ sexual offence that had the potential to encompass various distinct offences, from trafficking, rape and child sex abuse to deceptive sex. The legal history of the procurement is of particular importance as deception and questions of conditional consent remain deeply contested in modern criminal law.
Mechanisms for combining polyamide and epoxy and their effects on mechanical performance—A review
Authors: Heflin Diana G , Mansson Jan-Anders E
Published: September 2022

This paper provides an in-depth study in the various methods for toughening epoxy (EP) resin with polyamide (PA) across a range of length scales—from the atomic to the macroscopic. This allows for a fundamental understanding of the EP-PA system, as many of the atomic interactions and their kinetics inform the macroscopic mechanical properties. The kinetics of the EP-PA reaction prove that covalent bonding is energetically favorable, enabling chemical crosslinking between EP and PA. The two polymers can then mechanically interlock under a number of different processing conditions including forming a homogeneous mixture of the two, incorporating the PA into the EP in the form of fine particles, or adding the PA to an EP-fiber composite. Though each of these methods allows for the tailoring of processing conditions and final structures to an individual use, the literature shows that the underlying physical and chemical interactions can be applied to all EP-PA systems. Thus, lessons learned through the study of one EP-PA structure can be valuable in predicting the behavior of different EP-PA blends and material form combinations.
New scales of migration governance in the Mediterranean: Regional cities in the spotlight
Authors: Zapata-Barrero Ricard
Published: September 2022

Within the framework of Mediterranean migration studies and as a contribution to the emerging debate on the ‘local turn’, and on multiscalar approaches of region-making from different disciplines, the main objective of this article is to analyse an empirical trend that theoretically reinforces the view that cities can shape new regional domains. This city-region interface delimits the article’s two-sided argument. On one hand, the article argues that because of the increase of trans-Mediterranean relations, cities are contributing to regional-making; and, on the other hand, that this occurs through a critical process of State disengagement from the way in which the Mediterranean is configured today. After arguing for a Braudelian view of the Mediterranean as région de villes, the article conceptualizes the category of ‘regional cities’ within current geographical and international relations literature. Drawing on three examples of external city practices (city-to-city networks, city involvement in international non-governmental organization and city bilateral diplomacy with other cities), the article empirically illustrates, as a third step, the relevant different functionalities of the city that shape region-making. Finally, the article sets this empirical and theoretical focus within current European Union and State-based geo-migration politics as a top-down region-making failure. The purpose is to highlight the dissonance between the top-down region-making blockage and the historical bottom-up construct of the Mediterranean as a region of interconnected cities. This invites us to visualize regional cities as the basic component for a paradigm shift in Mediterranean migration governance.