Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

A comparative study of accuracy in major adaptive filters for motion artifact removal in sleep apnea tests.

Sleep apnea is probably the most common respiratory disorder; respiration and blood oxygen saturation (SpO2) are major concerns in sleep apnea and are also the two main parameters checked by polysomnography (PSG, the gold standard for diagnosing sleep apnea). In this study, we used a simple, non-invasive monitoring system based on photoplethysmography (PPG) to continuously monitor SpO2 and heart rate (HR) for individuals at home. Various breathing experiments were conducted to investigate the relationship between SpO2, HR, and apnea under different conditions, where two techniques (empirical formula and customized formula) for calculating SpO2 and two methods (resting HR and instantaneous HR) for assessing HR were compared. Various adaptive filters were implemented to compare the effectiveness in removing motion artifacts (MAs) during the tests. This study fills the gap in the literature by comparing the performance of different adaptive filters on estimating SpO2 and HR during apnea. The results showed that up-down finger motion introduced more MA than left-right motion, and the errors in SpO2 estimation were increased as the frequency of movement was increased; due to the low sampling frequency features of these tests, the insertion of adaptive filter increased the noise in the data instead of eliminating the MA for SpO2 estimation; the normal least mean squares (NLMS) filter is more effective in removing MA in HR estimation than other filters.

Self-relevance and the activation of attentional networks.

Recent theoretical accounts maintain that core components of attentional functioning are preferentially tuned to self-relevant information. Evidence in support of this viewpoint is equivocal, however, with research overly reliant on personally significant (i.e., familiar) stimulus inputs (e.g., faces, forenames) and a diverse range of methodologies. Addressing these limitations, here we utilised arbitrary items (i.e., geometric shapes) and administered the Attention Network Test (ANT) to establish the extent to which self-relevance (vs friend-relevance) moderates the three subsystems of attentional functioning-alerting, orienting, and executive control. The results revealed that only executive control was sensitive to the meaning of the stimuli, such that conflict resolution was enhanced following the presentation of self-associated compared with friend-associated shapes (i.e., cues). Probing the origin of this effect, a further computational analysis (i.e., Shrinking Spotlight Diffusion Model analysis) indicated that self-relevance facilitated the narrowing of visual attention. These findings highlight when and how the personal significance of otherwise trivial material modulates attentional processing.

Use of Lifesaving Medications by Athletic Trainers.

The athletic trainer's (AT's) emergency management skillset requires competency in the delivery of basic lifesaving medications. Some lifesaving medications have been a part of athletic training practice for decades, but that list has grown as ATs' practice settings have expanded, increasing the types of emergent conditions that the AT may have to treat. The 2020 Commission on Accreditation of Athletic Training Education (CAATE) curricular standards require that athletic training students be trained to administer the following: supplemental oxygen, nitroglycerine, low-dose aspirin, bronchodilators, epinephrine using an automated injection device, glucagon, and naloxone. Clinically, the conditions treated by these medications can be categorized as cardiac, respiratory, hypoglycemia, and anaphylaxis. All ATs should know the indications, contraindications, administration methods, and details of patient monitoring for each medication. Generally, these medications are safe and have clear indications for use and few contraindications. Although ATs are trained to administer these medications, they must consider state laws and local policies governing administration.

"A shovel or a shopping cart": lessons from ten years of disaster response by a student-led volunteer group.

Recent years have seen growing interest in enabling volunteers to play a more pronounced role in disaster response, and yet efforts to systematically analyse this crisis volunteer action, particularly among young people, have been surprisingly limited. This study examines the case of the Student Volunteer Army (SVA) in Aotearoa New Zealand, a student-led group which over the space of a decade has responded to multiple disasters, including earthquakes, floods, fires, a terrorist attack and the Covid-19 pandemic. Drawing on in-depth interviews, our analysis compares the practices adopted by the SVA in response to these different crises and identifies how members and supporters of the group have come to understand its capabilities, limitations, and conditions for effective operation. We present a framework of cross-cutting lessons of "why", "who", "when", "what" and "how" and demonstrate the ways they have been built upon for each new disaster mobilisation. In distilling, the key lessons of a youth-led crisis volunteer group that has mobilised for a spectrum of disasters, this paper contributes to theoretical understandings of how groups at a local level learn after sequential disasters, and the conditions and considerations that enable such groups to effectively-and repeatedly-"meet a need" in disaster response.

Effects of morphine on histamine release from two cell lines of canine mast cell tumor and on plasma histamine concentrations in dogs with cutaneous mast cell tumor.

OBJECTIVE: To determine the effects of morphine on histamine release from 2 canine mast cell tumor (MCT) cell lines and on plasma histamine concentrations in dogs with cutaneous MCTs. ANIMALS: 10 dogs with cutaneous MCT and 10 dogs with soft tissue sarcoma (STS). PROCEDURES: The study consisted of 2 phases. First, 2 canine MCT cell lines were exposed to 3 pharmacologically relevant morphine concentrations, and histamine concentrations were determined by an ELISA. Second, dogs with MCT or STS received 0.5 mg of morphine/kg, IM, before surgery for tumor excision. Clinical signs, respiratory rate, heart rate, arterial blood pressure, rectal temperature, and plasma histamine concentrations were recorded before and 5, 15, 30, and 60 minutes after morphine administration but prior to surgery. Data were compared by use of a 2-way ANOVA with the Sidak multiple comparisons test. RESULTS: In the first phase, canine MCT cell lines did not release histamine when exposed to pharmacologically relevant morphine concentrations. In the second phase, no differences were noted for heart rate, arterial blood pressure, and rectal temperature between MCT and STS groups. Plasma histamine concentrations did not significantly differ over time within groups and between groups. CONCLUSIONS AND CLINICAL RELEVANCE: No significant changes in histamine concentrations were noted for both in vitro and in vivo study phases, and no hemodynamic changes were noted for the in vivo study phase. These preliminary results suggested that morphine may be used safely in some dogs with MCT.

Explosive Quadriceps Strength Symmetry and Landing Mechanics Limb Symmetry After Anterior Cruciate Ligament Reconstruction in Females.

CONTEXT: Emerging evidence suggests that a lower quadriceps rate of torque development (RTD) after anterior cruciate ligament (ACL) reconstruction (ACLR) may be associated with altered landing mechanics. However, the influence of quadriceps RTD magnitude and limb symmetry on landing mechanics limb symmetry remains unknown. OBJECTIVE: To assess the influence of quadriceps RTD magnitude and limb symmetry on limb symmetry in sagittal-plane landing mechanics during functional landing tasks in females with or without ACLR. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 19 females with ACLR (age = 19.21 ± 1.81 years, height = 164.12 ± 6.97 cm, mass = 63.79 ± 7.59 kg, time after surgery = 20.05 ± 9.50 months) and 19 females serving as controls (age = 21.11 ± 3.28 years, height = 167.26 ± 7.26 cm, mass = 67.28 ± 9.25 kg). MAIN OUTCOME MEASURE(S): Landing mechanics were assessed during a double-legged (DL) jump-landing task, a single-legged jump-landing task, and a side-cutting task. Quadriceps RTD was collected during isometric muscle contractions. Separate stepwise multiple linear regression models were used to determine the variance in limb symmetry in the sagittal-plane knee moment at initial contact, peak vertical ground reaction force, and loading rate that could be explained by quadriceps RTD magnitude or limb symmetry, group (ACLR or control), and their interaction. RESULTS: In the ACLR group, greater limb symmetry in quadriceps RTD was associated with greater symmetry in sagittal-plane knee moment at initial contact during the DL task (P = .004). Peak vertical ground reaction force and loading rate could not be predicted by quadriceps RTD magnitude or limb symmetry, group, or their interaction during any task. CONCLUSIONS: Developing greater symmetry but not magnitude in quadriceps RTD likely enabled more symmetric sagittal-plane knee landing mechanics during the DL task in the ACLR group and thus may reduce the risk of a second ACL injury. Such a protective effect was not found during the single-legged or side-cutting tasks, which may indicate that these tasks do not allow for the compensatory landing mechanism of shifting load to the uninvolved limb that was possible during the DL task.

Study protocol: baby-OSCAR trial: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial.

BACKGROUND: The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks' gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic. METHODS: This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0-28+ 6 weeks' gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0-28+ 6 weeks' gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks' postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. DISCUSSION: Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks' postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age. TRIAL REGISTRATION: ISRCTN84264977 . Date assigned: 15/09/2010.

A biomechanical comparison of dominant and non-dominant limbs during a side-step cutting task.

Numerous studies have investigated anterior cruciate ligament (ACL) injury risk by examining gender differences in knee and hip biomechanics during a side-step cutting manoeuvre since it is known that ACL injury often occurs during such a task. Recent investigations have also examined lower extremity (LE) biomechanics during side-step cutting in individuals following ACL reconstruction (ACLR). Common research practice is to compare knee and hip biomechanics of the dominant limb between groups but this can add considerable complexity for clinicians and researchers. At this time, it is not known if there is a difference in LE biomechanics between the dominant and non-dominant limb during side-step cutting. Three-dimensional kinematics and kinetics were collected while 31 healthy participants performed five, side-step cutting manoeuvres with the dominant and non-dominant limbs. Knee and hip variables examined are those commonly investigated in ACL injury literature. There were no differences between limbs in all but one variable (knee internal rotation). These results demonstrate that healthy individuals exhibit little side-to-side differences in certain LE biomechanics when performing a side-step cutting manoeuvre. These findings can be utilised by clinicians when conducting dynamic evaluations of their ACLR patients and when developing injury prevention and rehabilitation programmes.

Phospholipid membranes drive abdominal aortic aneurysm development through stimulating coagulation factor activity.

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease with high mortality and limited treatment options. How blood lipids regulate AAA development is unknown. Here lipidomics and genetic models demonstrate a central role for procoagulant enzymatically oxidized phospholipids (eoxPL) in regulating AAA. Specifically, through activating coagulation, eoxPL either promoted or inhibited AAA depending on tissue localization. Ang II administration to ApoE-/- mice increased intravascular coagulation during AAA development. Lipidomics revealed large numbers of eoxPL formed within mouse and human AAA lesions. Deletion of eoxPL-generating enzymes (Alox12 or Alox15) or administration of the factor Xa inhibitor rivaroxaban significantly reduced AAA. Alox-deficient mice displayed constitutively dysregulated hemostasis, including a consumptive coagulopathy, characterized by compensatory increase in prothrombotic aminophospholipids (aPL) in circulating cell membranes. Intravenously administered procoagulant PL caused clotting factor activation and depletion, induced a bleeding defect, and significantly reduced AAA development. These data suggest that Alox deletion reduces AAA through diverting coagulation away from the vessel wall due to eoxPL deficiency, instead activating clotting factor consumption and depletion in the circulation. In mouse whole blood, ∼44 eoxPL molecular species formed within minutes of clot initiation. These were significantly elevated with ApoE-/- deletion, and many were absent in Alox-/- mice, identifying specific eoxPL that modulate AAA. Correlation networks demonstrated eoxPL belonged to subfamilies defined by oxylipin composition. Thus, procoagulant PL regulate AAA development through complex interactions with clotting factors. Modulation of the delicate balance between bleeding and thrombosis within either the vessel wall or circulation was revealed that can either drive or prevent disease development.

The Hoffmann reflex is different in men and women.

To compare the maximum Hoffmann reflex (H-reflex) and the maximum M-wave (H : M) ratio of the H-reflex in men and women when all participants showed similar saliva levels of estradiol and progesterone. This is a cohort design study involving healthy men and women with a mean age of 22.4±3.4 years. The H : M ratio of the H-reflex was assessed in women and men at a point in time when naturally occurring levels of estradiol and progesterone were similar. The female participants had a significantly higher H : M ratio compared with the male participants, whereas no differences in the saliva levels of progesterone and estradiol were detected. This is the first study to report differences between women and men in the H : M ratio of the H-reflex. An additional novel aspect of this study is that the assessments were performed when the levels of neuroactive sex hormones (estradiol and progesterone) were similar in all participants.

Live-cell confocal microscopy and quantitative 4D image analysis of anchor-cell invasion through the basement membrane in Caenorhabditis elegans.

Cell invasion through basement membrane (BM) barriers is crucial in development, leukocyte trafficking and the spread of cancer. The mechanisms that direct invasion, despite their importance in normal and disease states, are poorly understood, largely because of the inability to visualize dynamic cell-BM interactions in vivo. This protocol describes multichannel time-lapse confocal imaging of anchor-cell invasion in live Caenorhabditis elegans. Methods presented include outline-slide preparation and worm growth synchronization (15 min), mounting (20 min), image acquisition (20-180 min), image processing (20 min) and quantitative analysis (variable timing). The acquired images enable direct measurement of invasive dynamics including formation of invadopodia and cell-membrane protrusions, and removal of BM. This protocol can be combined with genetic analysis, molecular-activity probes and optogenetic approaches to uncover the molecular mechanisms underlying cell invasion. These methods can also be readily adapted by any worm laboratory for real-time analysis of cell migration, BM turnover and cell-membrane dynamics.

Temporal and spatial localization of prediction-error signals in the visual brain.

It has been suggested that the brain pre-empts changes in the environment through generating predictions, although real-time electrophysiological evidence of prediction violations in the domain of visual perception remain elusive. In a series of experiments we showed participants sequences of images that followed a predictable implied sequence or whose final image violated the implied sequence. Through careful design we were able to use the same final image transitions across predictable and unpredictable conditions, ensuring that any differences in neural responses were due only to preceding context and not to the images themselves. EEG and MEG recordings showed that early (N170) and mid-latency (N300) visual evoked potentials were robustly modulated by images that violated the implied sequence across a range of types of image change (expression deformations, rigid-rotations and visual field location). This modulation occurred irrespective of stimulus object category. Although the stimuli were static images, MEG source reconstruction of the early latency signal (N/M170) localized expectancy violation signals to brain areas associated with motion perception. Our findings suggest that the N/M170 can index mismatches between predicted and actual visual inputs in a system that predicts trajectories based on ongoing context. More generally we suggest that the N/M170 may reflect a "family" of brain signals generated across widespread regions of the visual brain indexing the resolution of top-down influences and incoming sensory data. This has important implications for understanding the N/M170 and investigating how the brain represents context to generate perceptual predictions.

Diagnosis of cancer as an emergency: a critical review of current evidence.

Many patients with cancer are diagnosed through an emergency presentation, which is associated with inferior clinical and patient-reported outcomes compared with those of patients who are diagnosed electively or through screening. Reducing the proportion of patients with cancer who are diagnosed as emergencies is, therefore, desirable; however, the optimal means of achieving this aim are uncertain owing to the involvement of different tumour, patient and health-care factors, often in combination. Most relevant evidence relates to patients with colorectal or lung cancer in a few economically developed countries, and defines emergency presentations contextually (that is, whether patients presented to emergency health-care services and/or received emergency treatment shortly before their diagnosis) as opposed to clinically (whether patients presented with life-threatening manifestations of their cancer). Consistent inequalities in the risk of emergency presentations by patient characteristics and cancer type have been described, but limited evidence is available on whether, and how, such presentations can be prevented. Evidence on patients' symptoms and health-care use before presentation as an emergency is sparse. In this Review, we describe the extent, causes and implications of a diagnosis of cancer following an emergency presentation, and provide recommendations for public health and health-care interventions, and research efforts aimed at addressing this under-researched aspect of cancer diagnosis.

Athletic Training and Public Health Summit.

OBJECTIVE: To introduce athletic trainers to the benefits of using a population-based approach to injury and illness prevention and to explore opportunities for partnering with public health professionals on these initiatives. BACKGROUND: Athletic trainers play leading roles in individual injury and illness prevention but are less familiar with policy development, evaluation, and implementation from a population-level standpoint. The Athletic Training and Public Health Summit was convened to understand, explore, and develop the intersection of athletic training and public health. CONCLUSIONS: To further the integration of athletic training within the public health arena, athletic trainers must expand their professional focus beyond the individual to the population level.

Imaging Polarization in Budding Yeast.

We describe methods for live-cell imaging of yeast cells that we have exploited to image yeast polarity establishment. As a rare event occurring on a fast time-scale, imaging polarization involves a trade-off between spatiotemporal resolution and long-term imaging without excessive phototoxicity. By synchronizing cells in a way that increases resistance to photodamage, we discovered unexpected aspects of polarization including transient intermediates with more than one polarity cluster, oscillatory clustering of polarity factors, and mobile "wandering" polarity sites.

MEG Adaptation Resolves the Spatiotemporal Characteristics of Face-Sensitive Brain Responses.

An unresolved goal in face perception is to identify brain areas involved in face processing and simultaneously understand the timing of their involvement. Currently, high spatial resolution imaging techniques identify the fusiform gyrus as subserving processing of invariant face features relating to identity. High temporal resolution imaging techniques localize an early latency evoked component-the N/M170-as having a major generator in the fusiform region; however, this evoked component is not believed to be associated with the processing of identity. To resolve this, we used novel magnetoencephalographic beamformer analyses to localize cortical regions in humans spatially with trial-by-trial activity that differentiated faces and objects and to interrogate their functional sensitivity by analyzing the effects of stimulus repetition. This demonstrated a temporal sequence of processing that provides category-level and then item-level invariance. The right fusiform gyrus showed adaptation to faces (not objects) at ∼150 ms after stimulus onset regardless of face identity; however, at the later latency of ∼200-300 ms, this area showed greater adaptation to repeated identity faces than to novel identities. This is consistent with an involvement of the fusiform region in both early and midlatency face-processing operations, with only the latter showing sensitivity to invariant face features relating to identity. SIGNIFICANCE STATEMENT: Neuroimaging techniques with high spatial-resolution have identified brain structures that are reliably activated when viewing faces and techniques with high temporal resolution have identified the time-varying temporal signature of the brain's response to faces. However, until now, colocalizing face-specific mechanisms in both time and space has proven notoriously difficult. Here, we used novel magnetoencephalographic analysis techniques to spatially localize cortical regions with trial-by-trial temporal activity that differentiates between faces and objects and to interrogate their functional sensitivity by analyzing effects of stimulus repetition on the time-locked signal. These analyses confirm a role for the right fusiform region in early to midlatency responses consistent with face identity processing and convincingly deliver upon magnetoencephalography's promise to resolve brain signals in time and space simultaneously.

Association Between Vitamin D Status and Maximal-Intensity Exercise Performance in Junior and Collegiate Hockey Players.

Recent evidence suggests that athletes are at risk for poor vitamin D status. This study used a cross-sectional design to investigate the strength of association between 25-hydroxyvitamin D (25(OH)D) concentration and measures of maximal-intensity exercise performance in competitive hockey players. Fifty-three collegiate and junior male ice hockey players training near Minneapolis, MN (44.9° N latitude) participated in the study during the off-season (May 16-June 28). Circulating 25(OH)D concentration, grip strength, vertical jump performance, and power production during the Wingate Anaerobic Test (WAnT) were evaluated. Despite no athletes with 25(OH)D concentration indicative of deficiency (<20 ng·mL), positive bivariate correlations were detected between vitamin D status, relative grip strength (p = 0.024), and peak power during the WAnT (p = 0.035). Only for relative grip strength (p = 0.043), did 25(OH)D concentration predict performance after adjusting for level of play, fat-free mass, fat mass, and self-reported total physical activity in sequential linear regression. Vitamin D status was positively associated with starting gradient (p = 0.020) during the squat jump, with higher concentrations associated with increased rate of force development in the initial portion of the jump. Interventional trials should investigate the impact of vitamin D supplementation on maximal-intensity exercise performance outcomes and rate of force development in large samples of vitamin D-deficient athletes while controlling for training exposure. Our data indicate that if vitamin D status is causally related to maximal-intensity exercise performance in athletes, the effect size is likely small.