Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Hybrid membrane distillation reverse electrodialysis configuration for water and energy recovery from human urine: An opportunity for off-grid decentralised sanitation.

The integration of membrane distillation with reverse electrodialysis has been investigated as a sustainable sanitation solution to provide clean water and electrical power from urine and waste heat. Reverse electrodialysis was integrated to provide the partial remixing of the concentrate (urine) and diluate (permeate) produced from the membrane distillation of urine. Broadly comparable power densities to those of a model salt solution (sodium chloride) were determined during evaluation of the individual and combined contribution of the various monovalent and multivalent inorganic and organic salt constituents in urine. Power densities were improved through raising feed-side temperature and increasing concentration in the concentrate, without observation of limiting behaviour imposed by non-ideal salt and water transport. A further unique contribution of this application is the limited volume of salt concentrate available, which demanded brine recycling to maximise energy recovery analogous to a battery, operating in a 'state of charge'. During recycle, around 47% of the Gibbs free energy was recoverable with up to 80% of the energy extractable before the concentration difference between the two solutions was halfway towards equilibrium which implies that energy recovery can be optimised with limited effect on permeate quality. This study has provided the first successful demonstration of an integrated MD-RED system for energy recovery from a limited resource, and evidences that the recovered power is sufficient to operate a range of low current fluid pumping technologies that could help deliver off-grid sanitation and clean water recovery at single household scale.

Effect of Repetitive Sub-concussive Head Impacts on Ocular Near Point of Convergence.

This study intended to examine effects of repetitive sub-concussive head impacts on ocular near point of convergence (NPC). 20 healthy young adult soccer players were assigned to either a heading or control group. Heading subjects completed 10 headers of soccer balls projected at a speed of 11.2 m/s. Control subjects did not perform heading. Linear head acceleration was measured with a triaxial accelerometer. The NPC assessment was performed at pre-, 0 h post-, and 24 h post-heading. During the NPC assessment participants were seated and a visual target was moved towards the eyes at 1cm/sec. The participant signaled when he/she experienced diplopia or deviation of the eye was observed, and the distance was recorded. The assessment was repeated twice and average NPC scores were used for further analysis. Soccer heading induced mean group head accelerations of 14.49±5.4 g. Mild head impacts led to an increased NPC distance, which was supported by a significant Group x Time interaction. In the heading group, 0 h post- and 24 h post-heading NPC scores were significantly receded compared to baseline. Conversely, NPC scores for the control group showed no difference over time. Our findings indicate that mild frontal head impacts affekt NPC for a minimum of 24 h-post heading, suggesting that oculomotor processes are disrupted, at least transiently, by repetitive mild head impact.

Vestibular and Oculomotor Assessments May Increase Accuracy of Subacute Concussion Assessment.

In this study, we collected and analyzed preliminary data for the internal consistency of a new condensed model to assess vestibular and oculomotor impairments following a concussion. We also examined this model's ability to discriminate concussed athletes from healthy controls. Each participant was tested in a concussion assessment protocol that consisted of the Neurocom's Sensory Organization Test (SOT), Balance Error Scoring System exam, and a series of 8 vestibular and oculomotor assessments. Of these 10 assessments, only the SOT, near point convergence, and the signs and symptoms (S/S) scores collected following optokinetic stimulation, the horizontal eye saccades test, and the gaze stabilization test were significantly correlated with health status, and were used in further analyses. Multivariate logistic regression for binary outcomes was employed and these beta weights were used to calculate the area under the receiver operating characteristic curve ( area under the curve). The best model supported by our findings suggest that an exam consisting of the 4 SOT sensory ratios, near point convergence, and the optokinetic stimulation signs and symptoms score are sensitive in discriminating concussed athletes from healthy controls (accuracy=98.6%, AUC=0.983). However, an even more parsimonious model consisting of only the optokinetic stimulation and gaze stabilization test S/S scores and near point convergence was found to be a sensitive model for discriminating concussed athletes from healthy controls (accuracy=94.4%, AUC=0.951) without the need for expensive equipment. Although more investigation is needed, these findings will be helpful to health professionals potentially providing them with a sensitive and specific battery of simple vestibular and oculomotor assessments for concussion management.

Collaborative study for the establishment of Ph. Eur. Biological Reference Preparation for Human tetanus immunoglobulin batch 2.

This publication describes the outcome of a project to develop a replacement European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Human tetanus immunoglobulin (TIg) as well as for the World Health Organization (WHO) International Standard (IS) for Tetanus Immunoglobulin, Human. Bulk TIg was kindly provided by a European manufacturer and was used to prepare the candidate standard. The candidate standard was freeze-dried and calibrated in an international collaborative study jointly co-ordinated by the Medicines & Healthcare products Regulatory Agency (MHRA) and the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe). The results of this study show that there was good agreement between laboratories for the potency estimates obtained for the candidate standard relative to the current WHO IS/Ph. Eur. BRP. The study also demonstrated that the candidate standard is suitable for use in Ph. Eur. assays for potency testing of TIg products and there was good agreement in the potency estimates obtained using the different assay methods included in the study. Accelerated degradation studies performed at the MHRA over a period of 4 years suggest that the freeze-dried candidate standard will be very stable. The candidate standard was established as Ph. Eur. BRP for Human tetanus immunoglobulin, batch 2 with an assigned potency of 45 IU/ampoule. The same preparation was also adopted by the WHO Expert Committee on Biological Standardization (ECBS) to serve as the WHO 2nd IS for Tetanus Immunoglobulin, Human (13/240).

Collaborative study for the establishment of Ph. Eur. Biological Reference Preparation for Human tetanus immunoglobulin batch 2.

This publication describes the outcome of a project to develop a replacement European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Human tetanus immunoglobulin (TIg) as well as for the World Health Organization (WHO) International Standard (IS) for Tetanus Immunoglobulin, Human. Bulk TIg was kindly provided by a European manufacturer and was used to prepare the candidate standard. The candidate standard was freeze-dried and calibrated in an international collaborative study jointly co-ordinated by the Medicines & Healthcare products Regulatory Agency (MHRA) and the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe). The results of this study show that there was good agreement between laboratories for the potency estimates obtained for the candidate standard relative to the current WHO IS/Ph. Eur. BRP. The study also demonstrated that the candidate standard is suitable for use in Ph. Eur. assays for potency testing of TIg products and there was good agreement in the potency estimates obtained using the different assay methods included in the study. Accelerated degradation studies performed at the MHRA over a period of 4 years suggest that the freeze-dried candidate standard will be very stable. The candidate standard was established as Ph. Eur. BRP for Human tetanus immunoglobulin, batch 2 with an assigned potency of 45 IU/ampoule. The same preparation was also adopted by the WHO Expert Committee on Biological Standardization (ECBS) to serve as the WHO 2nd IS for Tetanus Immunoglobulin, Human (13/240).

Post-operative Patient Portal Messaging is Associated With Return to the Emergency Department After Lumbar Spine Surgery.

STUDY DESIGN: Retrospective study. OBJECTIVE: To explore the association between patients undergoing lumbar spine surgery who message their care team via an electronic patient portal (EPP) post-operatively and emergency department (ED) visits within 90 days of surgery. SUMMARY OF BACKGROUND DATA: Secure patient messaging through electronic patient portals has grown over recent years. Despite its frequent utilization by patients to engage with their care team, its association with clinical outcomes remains unknown in spine surgery. METHODS: This study was approved by our Institutional Review Board. Inclusion criteria were adults who underwent single-stage lumbar spine surgery between January 2016-June 2023. Patients with incomplete information, multi-stage surgeries, and those who died within 90 days of surgery were excluded. Patient sociodemographic, surgical, hospital readmission, and patient-provider engagement data were collected. RESULTS: A total of 13,135 patients were included. A total of 1,711 patients (13%) had a post-operative ED visit, and 4,791 patients (36%) used the patient portal to send a message after surgery. Sending a post-operative patient message after undergoing lumbar spine surgery was associated with an increased likelihood of having an ED visit that does not lead to readmission (1.29 (1.10-1.53), P = 0.002). Patients with high school degrees were more likely to have an ED visit without readmission (1.33 (1.08-1.65), P = 0.008). CONCLUSION: Patients at a higher risk of presenting to the ED post-operatively should be identified and may benefit from additional counseling and access to the care team virtually to limit unnecessary healthcare utilization. Focusing on patients who reach out via EPP messaging post-operatively may be a good target patient group to address first. Future research is needed to investigate the possible health literacy and other socioeconomic barriers affecting these patients so that appropriate, more cost-effective resources can be utilized to avoid clinically unnecessary and costly ED visits.

Acute changes in postural control after soccer heading.

This study intended to determine if an acute bout of soccer heading alters postural control and pronounced self-reported symptoms of cerebral concussion. Collegiate soccer players were randomly assigned to one of 2 groups. Each participant completed a baseline postural control assessment prior to heading. Participants either simulated (control group; CG) or performed (experimental group; EG) 10 headers at 11.2 m/s in 10 min. The postural assessment was repeated post heading at hrs 1, 24, and 48. The postural control parameter assessed was the root mean square (RMS) of the center of mass (COM). COM RMS were calculated for the anterior-posterior (AP) and medial-lateral (ML) time series. Compared to the CG, for the AP and ML time series COM RMS values were significantly higher in the EG at hr 24 (p <0.05). An acute bout of heading results in quantifiable alterations in postural control that are detectable 24 h post heading and dissipate within an additional 24 h. The significant findings may be due to the dynamic postural control assessment that incorporated robust discordant environmental conditions.

Optimization of the formulation for a candidate lyophilised tetanus toxoid reference preparation.

Tetanus toxoid is a vital primary reference material used for standardization of assays required to establish the antigenic purity of tetanus toxoid for vaccine production. Several formulations were assessed and ampouled fills of each formulation lyophilised. The relative Lf content determined by Ramon flocculation, SRD, and ELISA assays was measured. The stability of the tetanus toxoid activity in each formulation was assessed by accelerated degradation studies. Formulations containing glycine were not suitable in flocculation tests but both sorbitol and trehalose formulations were. The trehalose/sodium chloride formulation had a good appearance, showed good activity in all assays and maintained its activity best under stress conditions. This formulation has been applied to a large scale batch of ampoules prepared as a WHO candidate replacement standard, evaluated in a collaborative study and accepted as a replacement WHO IS for use in flocculation test (WHO ECBS, October 2007, ref no BS/07.2061). The stability of this formulation was also excellent for the large scale batch. The benefits of using thermal analysis and freeze drying microscopy coupled with small scale lyophilisation trials in order to screen formulations for the preparation of batches of biological reference materials are demonstrated.

Population dynamics of soybean aphid and biotic mortality at the edge of its range.

The soybean aphid, Aphis glycines Matsumura, was introduced to north central North America from Asia in 2000, and it has become a major pest of soybean, Glycine max (L.) Merr. Understanding how natural enemies impact aphid populations in the field is an important component in developing a comprehensive management plan. We examined the impact of naturally occurring predators in the field by using exclusion cages during July-August 2004 and 2005. Field cages of different mesh diameters were used to exclude different sizes of natural enemies from aphid-infested plots. Plots were surveyed twice weekly for A. glycines and natural enemies. Densities were recorded. Cage effects on mean temperature and soybean growth were found to be insignificant. Significant differences in aphid density were found between treatments in both years of the study (2004 and 2005); however, aphid densities between years were highly variable. Orius insidiosus (Say) was the most commonly occurring predator in the field. Other natural enemies were present in both years but not in high numbers. Parasitoids were present in both years, but their numbers did not suppress aphid densities. Treatment differences within years were related to the abundance of natural enemies. The large differences in aphid abundance between years were associated with the higher number of O. insidiosus found in the field in 2005 (416 total O. insidiosus) than in 2004 (149 total O. insidiosus). This study suggests that naturally occurring predators, primarily O. insidiosus, can have a large impact on A. glycines populations when predator populations are established before initial A. glycines colonization.

Visual-vestibular processing deficits in mild traumatic brain injury.

BACKGROUND: The search for reliable and valid signs and symptoms of mild traumatic brain injury (mTBI), commonly synonymous with concussion, has lead to a growing body of evidence that individuals with long-lasting, unremitting impairments often experience visual and vestibular symptoms, such as dizziness, postural and gait disturbances. OBJECTIVE: Investigate the role of visual-vestibular processing deficits following concussion. METHODS: A number of clinically accepted vestibular, oculomotor, and balance assessments as well as a novel virtual reality (VR)-based balance assessment device were used to assess adults with post-acute concussion (n = 14) in comparison to a healthy age-matched cohort (n = 58). RESULTS: Significant between-group differences were found with the VR-based balance device (p = 0.001), with dynamic visual motion emerging as the most discriminating balance condition. The symptom reports collected after performing the oculomotor and vestibular tests: rapid alternating horizontal eye saccades, optokinetic stimulation, and gaze stabilization, were all sensitive to health status (p < 0.05), despite the absence of oculomotor abnormalities being observed, except for near-point convergence. The BESS, King-Devick, and Dynamic Visual Acuity tests did not detect between-group differences. CONCLUSION: Postural and visual-vestibular tasks most closely linked to spatial and self-motion perception had the greatest discriminatory outcomes. The current findings suggest that mesencephalic and parieto-occipital centers and pathways may be involved in concussion.

Botulinum type A toxin neutralisation by specific IgG and its fragments: a comparison of mouse systemic toxicity and local flaccid paralysis assays.

In this study, we have compared two in vivo assay methods to measure the type A botulinum toxin neutralising activity of specific immunoglobulin G (IgG) and its fragments (F(ab')(2), Fab', Fab) purified from pentavalent botulinum antisera raised in goats. Each assay method was repeated on three separate occasions in mice and relative potencies calculated with respect to a type A equine reference antitoxin. The conventional assay, which measures the number of mice surviving typically after 72 or 96 h following the intraperitoneal administration of a mixture of toxin and antitoxin, gave the following order of potency IgG>F(ab')(2)>Fab'>Fab (6.8>4.7>3.5>2.6 IU/mg). Differences in potency are likely to be due to differences in the pharmacokinetics of the antitoxins, which are related to their molecular weight. The alternative local flaccid paralysis assay, where toxin and antitoxin are injected subcutaneously into the left inguinocrural region, gave results with a narrower range of activities: IgG>Fab'>F(ab')(2)>Fab (6.0>5.9>5.5>4.6 IU/mg). Comparison of the two assay methods showed no significant differences for IgG, F(ab')(2) or Fab', although the Fab fragment was significantly more potent in the non-lethal assay probably because of the reduced influence of antitoxin pharmacokinetics in this localised assay. These findings show that a local flaccid paralysis assay provides a less time consuming and more humane alternative to the lethal assay for the potency testing of botulinum IgG and F(ab')(2) antitoxins.

Cleaning Puparia for Forensic Analysis.

We tested procedures for removing adipocere from insect samples to allow identification. An acceptable procedure was determined: (i) Samples were sorted in petri dishes with 75% alcohol to remove any larvae, adult insects, or other soft-bodied material. (ii) Samples of up to 24 puparia were placed in a vial with 15 mL of 95% acetone, capped, and vortexed for a total of 30-90 sec in 10- to 15-sec bursts. This step removed large masses of adipocere or soil from specimen. (iii) Specimens were removed from acetone and placed in a vial of 15 mL of 2% potassium hydroxide (KOH) and vortexed in 10- to 15-sec bursts until all puparia appeared clean (with our samples this required a total of 60-120 sec). (iv) Specimens were removed from the 2% KOH, placed in 75% ethanol, and examined microscopically. (v) Material was stored in 75% ethanol for identification and long-term preservation.

Cardiac Na+ pump current-voltage relationships at various transmembrane gradients of the pumped cations.

Thermodynamic considerations predict changes of the Na+ pump current (Ip)-voltage (V) relationship of animal cells upon variations of the electrochemical gradients against which cations must be pumped. Experimental data in support of the predictions are sparse. Therefore, the effect on the Ip-V relationship of various electrochemical gradients for pumped Na+ and Cs+ was studied at constant deltaGATP (approximately -39kJ/mol in cardioballs from sheep Purkinje fibres. Control of the subsarcolemmal ionic concentrations during whole-cell recording was ensured by activation of Ip below its half maximal activity or by measuring the initial Ip following reactivation of the Na+/K+ pump. With gradients close to physiological conditions Ip was outward over the entire voltage range and the Ip-V relationship showed a maximum near zero potential. Steepening the ionic gradients diminished the Ip amplitude and outward pump current was no longer detectable between -65 mV and -110 mV. Flattened ionic gradients increased the Ip amplitude and shifted apparently the reversal potential Erev to more negative values. These changes are in line with theoretical considerations. The measured Ip-V relationships were fitted by curves computed on the basis of a simplified Post-Albers scheme of Na+/Cs+ pumping. The increased Ip amplitude at flat ionic gradients was due to a decrease of [Cs+]o for half maximal Ip activation. The maximal Ip amplitude remained unaffected

Mitral valve prolapse syndrome in children with Duchenne's progressive muscular dystrophy.

Myocardial function was evaluated prospectively by noninvasive methods in 20 boys with clinical, biochemical, muscle biopsy, and electromyographic evidence of Duchenne's progressive muscular dystrophy. Auscultatory evidence of a nonejection systolic click suggested mitral valve prolapse (MVP) syndrome in seven patients. Phonocardiography disclosed that the click was mid-systolic in four patients and early in three. Echocardiographic features consistent with this diagnosis were identified in all seven patients and in an additional four. One of these had an apical pansystolic murmur, suggestive of mitral regurgitation, whereas in the other three, prolapse of the mitral valve was "silent". Echocardiographic findings included an abrupt midsystolic, posterior motion (greater than 3 mm beyond the CD line) in five patients, multiple sequence echoes in six, and posterior coaptation of the mitral valve near the left atrial wall in six. The features most characteristic of MVP syndrome was a smooth, pansystolic, anteriorly concave (hammock-like) posterior motion deviating more than 3 mm beyond the CD line. Among the remaining nine patients who did not have echocardiographic evidence of prolapsing mitral valve, none had an early, middle or late nonejection systolic click or a heart murmur, although four patients in this group had moderate to severe scoliosis. These observations document of occurrence of MVP syndrome in children with Duchenne's muscular dystrophy and indicate that its prevalence is high. We speculate that prolapse of the mitral valve in these patients is an expression of the underlying cardiomyopathy characteristic of Duchenne's muscular dystrophy rather than an isolated, dystrophic involvement of the mitral valve leaflets.

Systolic time interval characteristics in children with Duchenne's progressive muscular dystrophy.

Systolic time interval (STI) characteristics of 17 boys with Duchenne's muscular dystrophy (DMD) were compared with those of 80 normal boys who served as control subjects. The heart rate decreased linearly with age in normal control subjects (r = -.47, P less than .01). By contrast, heart rate was significantly higher in patients with DMD (P less than .001) and tended to increase further with age. Each STI variable for normal control subjects increased significantly with age (P less than or equal to .01); QII, left ventricular ejection time (LVET), and pre-ejection period (PEP), in addition, decreased with increasing heart rate (P less than or equal to .05). In dystrophic patients QII and LVET decreased with increasing heart rate (P less than .001) but were not influenced by age. None of the other STI values in dystrophic patients was significantly influenced by either age or heart rate. Mean QII, LVET, and QI were shorter and PEP, isometric contraction time (ICT), and PEP/LVET ratio were longer (P less than .001) for DMD patients than for normal control subjects. In 13/17 patients, QII and LVET were below the 95% confidence interval of the normal mean, whereas PEP, ICT, and PEP/LVET exceeded the upper limits of normal in 8, 9 and 11 patients, respectively. For dystrophic patients, the difference (delta) between the observed values and those predicted from regression equations for normal control subjects was lower for QII, LVET, and QI (P less than .01) but higher for PEP (P less than .04), ICT, and PEP/LVET ratio (P less than .001). delta QII and delta LVET increased with age (P = .001 and .032, respectively). Duchenne's muscular dystrophy is thus documented to be associated with substantial alterations in STI characteristics that suggest a compromise of global left ventricular performance. Some of these abnormalities increase with age, probably reflecting the progressive cardiomyopathy characteristics of this disease.

Effects of variations in flow on aortic valve area in aortic stenosis based on in vivo planimetry of aortic valve area by multiplane transesophageal echocardiography.

This study provides evidence that acute changes in stroke volume and cardiac output do not result in significant alterations in the anatomic AVA measured with multiplane TEE in patients with AS of moderate or severe degree. Thus, TEE could be useful in the assessment of severity of AS in both low- and high-output states.

Neonatal novelty exposure modulates hippocampal volumetric asymmetry in the rat.

Early life environmental manipulations have been shown to affect hippocampal-dependent learning, hippocampal volume and cerebral lateralization. In this study, we investigated the effects of neonatal stimulation on hippocampal volumetric asymmetry. Long-Evans hooded rats were exposed to a novel non-home environment 3 min daily for the first 3 weeks of life. Histological measures of the left and right hippocampus were made at 8 months of age. We found that neonatal novelty exposure resulted in a long-lasting change in hippocampal volumetric asymmetry. Specifically, this brief and transient early life stimulation increased the right hippocampal volumetric dominance at mid-adulthood.

Suicide intervention training evaluation: a preliminary report.

To date, very little work has been done on evaluating training in suicide intervention. This study developed and piloted a comprehensive method for evaluating suicide intervention training by applying three studies of immediate training effects on (a) suicide intervention abilities, (b) attitudes to suicide and suicide intervention, and (c) knowledge about suicide. The focus of the evaluation was a broadly used 2-day suicide intervention training program. Changes in suicide intervention abilities were measured by the Suicide Intervention Response Inventory (SIRI) and by performance in simulated suicide intervention situations, scored with the Suicide Intervention Protocol (SIP). Subjects consisted of 19 workshop participants in a pre-post condition and 17 participants in a post-test only condition. Results indicated significant increases in skills in suicide intervention situations. No significant effects were noted on the SIRI. Results from the attitudes and knowledge studies were very preliminary. They are reported here so that others may become aware of the methodology being used and the status of evaluation of the target program. Implications for further research are discussed.