Enhancing the Diagnostic Utility of ASL Imaging in Temporal Lobe Epilepsy through FlowGAN: An ASL to PET Image Translation Framework.

Background and Significance: Positron Emission Tomography (PET) using fluorodeoxyglucose (FDG-PET) is a standard imaging modality for detecting areas of hypometabolism associated with the seizure onset zone (SOZ) in temporal lobe epilepsy (TLE). However, FDG-PET is costly and involves the use of a radioactive tracer. Arterial Spin Labeling (ASL) offers an MRI-based quantification of cerebral blood flow (CBF) that could also help localize the SOZ, but its performance in doing so, relative to FDG-PET, is limited. In this study, we seek to improve ASL's diagnostic performance by developing a deep learning framework for synthesizing FDG-PET-like images from ASL and structural MRI inputs. Methods: We included 68 epilepsy patients, out of which 36 had well lateralized TLE. We compared the coupling between FDG-PET and ASL CBF values in different brain regions, as well as the asymmetry of these values across the brain. We additionally assessed each modality's ability to lateralize the SOZ across brain regions. Using our paired PET-ASL data, we developed FlowGAN, a generative adversarial neural network (GAN) that synthesizes PET-like images from ASL and T1-weighted MRI inputs. We tested our synthetic PET images against the actual PET images of subjects to assess their ability to reproduce clinically meaningful hypometabolism and asymmetries in TLE. Results: We found variable coupling between PET and ASL CBF values across brain regions. PET and ASL had high coupling in neocortical temporal and frontal brain regions (Spearman's r > 0.30, p < 0.05) but low coupling in mesial temporal structures (Spearman's r < 0.30, p > 0.05). Both whole brain PET and ASL CBF asymmetry values provided good separability between left and right TLE subjects, but PET (AUC = 0.96, 95% CI: [0.88, 1.00]) outperformed ASL (AUC = 0.81; 95% CI: [0.65, 0.96]). FlowGAN-generated images demonstrated high structural similarity to actual PET images (SSIM = 0.85). Globally, asymmetry values were better correlated between synthetic PET and original PET than between ASL CBF and original PET, with a mean correlation increase of 0.15 (95% CI: [0.07, 0.24], p<0.001, Cohen's d = 0.91). Furthermore, regions that had poor ASL-PET correlation (e.g. mesial temporal structures) showed the greatest improvement with synthetic PET images. Conclusions: FlowGAN improves ASL's diagnostic performance, generating synthetic PET images that closely mimic actual FDG-PET in depicting hypometabolism associated with TLE. This approach could improve non-invasive SOZ localization, offering a promising tool for epilepsy presurgical assessment. It potentially broadens the applicability of ASL in clinical practice and could reduce reliance on FDG-PET for epilepsy and other neurological disorders.

Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Perspectives on long-acting formulations of pre-exposure prophylaxis (PrEP) among men who have sex with men who are non-adherent to daily oral PrEP in the United States.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. RESULTS: Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. CONCLUSION: Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.

Kinematic Gait Impairments in Children with Clubfeet Treated by the Ponseti Method: A Systematic Review and Meta-Analysis.

BACKGROUND: Being aware of possible gait impairments in Ponseti-treated clubfoot children might be useful for optimizing initial and additional treatment. Therefore, this systematic review and meta-analysis aimed to identify kinematic gait abnormalities in children with clubfoot treated with the Ponseti method (with and without relapse). METHODS: A systematic search was conducted. Studies comparing kinematic gait parameters of Ponseti-treated clubfoot children to healthy controls were included. Meta-analyses and qualitative analyses were conducted on the extracted data. RESULTS: Twenty studies were identified. Twelve of the 153 reported kinematic outcome measures could be included in the meta-analysis. Plantarflexion at push-off, maximum ankle dorsiflexion during the swing, maximal plantarflexion, and ankle range of motion was significantly lower in Ponseti-treated clubfoot children. Ponseti-treated clubfoot children showed more internal foot progression. Qualitative analysis revealed 51 parameters in which pre-treatment relapse clubfeet deviated from healthy controls. CONCLUSIONS: Ponseti-treated clubfoot children showed several kinematic gait differences from healthy controls. In future studies, homogeneity in measured variables and study population and implementation of multi-segmental foot models will aid in comparing studies and understanding clubfoot complexity and treatment outcomes. The question remains as to what functional problems gait impairments lead to and whether additional treatment could address these problems.

Remote effects of temporal lobe epilepsy surgery: Long-term morphological changes after surgical resection.

OBJECTIVE: Epilepsy surgery is an effective treatment for drug-resistant patients. However, how different surgical approaches affect long-term brain structure remains poorly characterized. Here, we present a semiautomated method for quantifying structural changes after epilepsy surgery and compare the remote structural effects of two approaches, anterior temporal lobectomy (ATL), and selective amygdalohippocampectomy (SAH). METHODS: We studied 36 temporal lobe epilepsy patients who underwent resective surgery (ATL = 22, SAH = 14). All patients received same-scanner MR imaging preoperatively and postoperatively (mean 2 years). To analyze postoperative structural changes, we segmented the resection zone and modified the Advanced Normalization Tools (ANTs) longitudinal cortical pipeline to account for resections. We compared global and regional annualized cortical thinning between surgical treatments. RESULTS: Across procedures, there was significant cortical thinning in the ipsilateral insula, fusiform, pericalcarine, and several temporal lobe regions outside the resection zone as well as the contralateral hippocampus. Additionally, increased postoperative cortical thickness was seen in the supramarginal gyrus. Patients treated with ATL exhibited greater annualized cortical thinning compared with SAH cases (ATL: -0.08 ± 0.11 mm per year, SAH: -0.01 ± 0.02 mm per year, t = 2.99, P = 0.006). There were focal postoperative differences between the two treatment groups in the ipsilateral insula (P = 0.039, corrected). Annualized cortical thinning rates correlated with preoperative cortical thickness (r = 0.60, P < 0.001) and had weaker associations with age at surgery (r = -0.33, P = 0.051) and disease duration (r = -0.42, P = 0.058). SIGNIFICANCE: Our evidence suggests that selective procedures are associated with less cortical thinning and that earlier surgical intervention may reduce long-term impacts on brain structure.

Participation and Motor Abilities in Children Aged 5 to 9 Years With Idiopathic Clubfeet After Treatment With the Ponseti Method.

BACKGROUND: Functioning in children consists of different aspects, including their ability to execute activities and participate in life situations. Several studies on children with clubfeet showed limited motor abilities and walking capacity compared with healthy control children, while other studies showed comparable athletic abilities and gross motor development. Although participation in activities of daily life plays an important role in the development of children, this has not yet been investigated in children with clubfeet. The study aims to determine the level of parents' perceived motor ability and participation in Ponseti-treated children with clubfeet compared with age-matched healthy controls. METHODS: Parents of children aged 5 to 9 years with and without idiopathic Ponseti-treated clubfeet were asked to complete an online questionnaire about their child's motor abilities and participation level using the Dutch version of the Assessment of Life Habits for Children (LIFE-H) version 3 to assess participation and the Dutch Movement Assessment Battery for Children-2 Checklist (MABC-2 Checklist) to assess motor abilities. Statistical analysis focused on differences between groups and the relationship between motor abilities and level of participation. RESULTS: Questionnaires of 86 children with clubfeet (mean age 7.1, 73% boys) and 62 controls (age 6.7, 53% boys) were analyzed. Despite a large variation, results showed no significant differences between groups on the total scores of the LIFE-H and the MABC-2 Checklist. Children with clubfeet, however, scored lower on Mobility and better on the categories Communication and Responsibility of the LIFE-H. Furthermore, children with clubfeet showed lower scores on the MABC-2 Checklist subscale "movement in a static and/or predictable environment." High levels of the parents' perceived participation correlate with good results, as perceived by the parents, in motor ability. CONCLUSIONS: Although differences on some aspects of motor ability and participation existed, children with clubfeet in general showed high levels of parents' perceived motor ability and participation. High levels of participation correlated with good results in motor ability. LEVEL OF EVIDENCE: Level II.

Multi-contrast high-field quality image synthesis for portable low-field MRI using generative adversarial networks and paired data.

Introduction: Portable low-field strength (64mT) MRI scanners promise to increase access to neuroimaging for clinical and research purposes, however these devices produce lower quality images compared to high-field scanners. In this study, we developed and evaluated a deep learning architecture to generate high-field quality brain images from low-field inputs using a paired dataset of multiple sclerosis (MS) patients scanned at 64mT and 3T. Methods: A total of 49 MS patients were scanned on portable 64mT and standard 3T scanners at Penn (n=25) or the National Institutes of Health (NIH, n=24) with T1-weighted, T2-weighted and FLAIR acquisitions. Using this paired data, we developed a generative adversarial network (GAN) architecture for low- to high-field image translation (LowGAN). We then evaluated synthesized images with respect to image quality, brain morphometry, and white matter lesions. Results: Synthetic high-field images demonstrated visually superior quality compared to low-field inputs and significantly higher normalized cross-correlation (NCC) to actual high-field images for T1 (p=0.001) and FLAIR (p<0.001) contrasts. LowGAN generally outperformed the current state-of-the-art for low-field volumetrics. For example, thalamic, lateral ventricle, and total cortical volumes in LowGAN outputs did not differ significantly from 3T measurements. Synthetic outputs preserved MS lesions and captured a known inverse relationship between total lesion volume and thalamic volume. Conclusions: LowGAN generates synthetic high-field images with comparable visual and quantitative quality to actual high-field scans. Enhancing portable MRI image quality could add value and boost clinician confidence, enabling wider adoption of this technology.

Do Blood group and Sickle cell trait protect against placental malaria?

Blood group O is reported to confer some degree of protection from severe malaria in endemic setting. This protection is believed to be due to reduced and smaller rosette formation in people of blood group O which can easily be cleared by the host immune system. Also, sickle cell trait (HbAS) is reported to disrupt the adhesion of infected erythrocytes to microvascular endothelial walls, which could protect pregnant women from placental malaria. We determined the association between HbAS and ABO blood group, and placental malaria amongst pregnant women of all parities. The study enrolled 221 pregnant women. Peripheral blood samples were taken for malaria smears, ABO blood grouping and haemoglobin (Hb) electrophoresis. A structured questionnaire was used to age, bed net usage, and the number of Sulphadoxine-pyrimethamine (SP) doses taken by a pregnant woman. Two hundred and twenty-one (221) pregnant women were enrolled and out of this number, 110 (49.8%) were primiparae and 111 (50.2%) multiparae, with a mean age of 23.7±5.2. Placental malaria (PM) prevalence by PCR detection was 19.4% (43/221). Of those who were malaria positive 58.1% (25/43) were primiparae. Primiparae who are of blood group O were more susceptible to PM [P=0.04, (OR); 2.85, 95% (Cl), 1.12-9.01]. But sickle cell trait did not reduce the prevalence of PM [P=0.84 (OR); 0.92, 95% (Cl), 0.43-1.99]. Non-blood group O primiparae women were protected against placental malaria. This could be why some primiparae women are protected from PM, just like multiparae women.

Quality of life of clubfoot patients during the brace period of the Ponseti method.

PURPOSE: Quantifying the quality of life in clubfoot patients during bracing following the Ponseti method compared with healthy controls. METHODS: Data collected during the brace period of the Ponseti method and of a reference sample was retrospectively analyzed to investigate health-related quality of life scale (TAPQOL) in clubfoot patients compared with healthy controls. The TAPQOL instrument consists of 12 subscales comprising the 4 domains of health-related quality of life namely physical, social, emotional and cognitive functioning. RESULTS: Responses of 80 parents of clubfoot patients and 238 parents of healthy controls were analyzed. On average both study groups scored high on the 4 domains of the TAPQOL instrument. The clubfoot group scored significantly (p<0.0125) lower on the subscales motor functioning, sleep, lung and skin problems during bracing. No difference was observed between the study groups in the year the bracing had ended. CONCLUSION: Dutch clubfoot patients show an overall good health related quality of life. However, during the brace phase of the Ponseti treatment they score lower in subscales in the physical functioning domain. These results can be used in the counselling of parent and might alleviate some concerns that parents have about the bracing period. LEVEL OF EVIDENCE: Level III, Case control study.

Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment.

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Deep learning-based automated segmentation of resection cavities on postsurgical epilepsy MRI.

Accurate segmentation of surgical resection sites is critical for clinical assessments and neuroimaging research applications, including resection extent determination, predictive modeling of surgery outcome, and masking image processing near resection sites. In this study, an automated resection cavity segmentation algorithm is developed for analyzing postoperative MRI of epilepsy patients and deployed in an easy-to-use graphical user interface (GUI) that estimates remnant brain volumes, including postsurgical hippocampal remnant tissue. This retrospective study included postoperative T1-weighted MRI from 62 temporal lobe epilepsy (TLE) patients who underwent resective surgery. The resection site was manually segmented and reviewed by a neuroradiologist (JMS). A majority vote ensemble algorithm was used to segment surgical resections, using 3 U-Net convolutional neural networks trained on axial, coronal, and sagittal slices, respectively. The algorithm was trained using 5-fold cross validation, with data partitioned into training (N = 27) testing (N = 9), and validation (N = 9) sets, and evaluated on a separate held-out test set (N = 17). Algorithm performance was assessed using Dice-Sørensen coefficient (DSC), Hausdorff distance, and volume estimates. Additionally, we deploy a fully-automated, GUI-based pipeline that compares resection segmentations with preoperative imaging and reports estimates of resected brain structures. The cross-validation and held-out test median DSCs were 0.84 ± 0.08 and 0.74 ± 0.22 (median ± interquartile range) respectively, which approach inter-rater reliability between radiologists (0.84-0.86) as reported in the literature. Median 95 % Hausdorff distances were 3.6 mm and 4.0 mm respectively, indicating high segmentation boundary confidence. Automated and manual resection volume estimates were highly correlated for both cross-validation (r = 0.94, p < 0.0001) and held-out test subjects (r = 0.87, p < 0.0001). Automated and manual segmentations overlapped in all 62 subjects, indicating a low false negative rate. In control subjects (N = 40), the classifier segmented no voxels (N = 33), <50 voxels (N = 5), or a small volumes<0.5 cm3 (N = 2), indicating a low false positive rate that can be controlled via thresholding. There was strong agreement between postoperative hippocampal remnant volumes determined using automated and manual resection segmentations (r = 0.90, p < 0.0001, mean absolute error = 6.3 %), indicating that automated resection segmentations can permit quantification of postoperative brain volumes after epilepsy surgery. Applications include quantification of postoperative remnant brain volumes, correction of deformable registration, and localization of removed brain regions for network modeling.

Facilitators for retaining men who have sex with men in pre-exposure prophylaxis care in real world clinic settings within the United States.

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. RESULTS: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). DISCUSSION: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.

Sensitivity of portable low-field magnetic resonance imaging for multiple sclerosis lesions.

Magnetic resonance imaging (MRI) is a fundamental tool in the diagnosis and management of neurological diseases such as multiple sclerosis (MS). New portable, low-field strength, MRI scanners could potentially lower financial and technical barriers to neuroimaging and reach underserved or disabled populations, but the sensitivity of these devices for MS lesions is unknown. We sought to determine if white matter lesions can be detected on a portable 64mT scanner, compare automated lesion segmentations and total lesion volume between paired 3T and 64mT scans, identify features that contribute to lesion detection accuracy, and explore super-resolution imaging at low-field. In this prospective, cross-sectional study, same-day brain MRI (FLAIR, T1w, and T2w) scans were collected from 36 adults (32 women; mean age, 50 ± 14 years) with known or suspected MS using Siemens 3T (FLAIR: 1 mm isotropic, T1w: 1 mm isotropic, and T2w: 0.34-0.5 × 0.34-0.5 × 3-5 mm) and Hyperfine 64mT (FLAIR: 1.6 × 1.6 × 5 mm, T1w: 1.5 × 1.5 × 5 mm, and T2w: 1.5 × 1.5 × 5 mm) scanners at two centers. Images were reviewed by neuroradiologists. MS lesions were measured manually and segmented using an automated algorithm. Statistical analyses assessed accuracy and variability of segmentations across scanners and systematic scanner biases in automated volumetric measurements. Lesions were identified on 64mT scans in 94% (31/33) of patients with confirmed MS. The average smallest lesions manually detected were 5.7 ± 1.3 mm in maximum diameter at 64mT vs 2.1 ± 0.6 mm at 3T, approaching the spatial resolution of the respective scanner sequences (3T: 1 mm, 64mT: 5 mm slice thickness). Automated lesion volume estimates were highly correlated between 3T and 64mT scans (r = 0.89, p < 0.001). Bland-Altman analysis identified bias in 64mT segmentations (mean = 1.6 ml, standard error = 5.2 ml, limits of agreement = -19.0-15.9 ml), which over-estimated low lesion volume and under-estimated high volume (r = 0.74, p < 0.001). Visual inspection revealed over-segmentation was driven venous hyperintensities on 64mT T2-FLAIR. Lesion size drove segmentation accuracy, with 93% of lesions > 1.0 ml and all lesions > 1.5 ml being detected. Using multi-acquisition volume averaging, we were able to generate 1.6 mm isotropic images on the 64mT device. Overall, our results demonstrate that in established MS, a portable 64mT MRI scanner can identify white matter lesions, and that automated estimates of total lesion volume correlate with measurements from 3T scans.

Normative intracranial EEG maps epileptogenic tissues in focal epilepsy.

Planning surgery for patients with medically refractory epilepsy often requires recording seizures using intracranial EEG. Quantitative measures derived from interictal intracranial EEG yield potentially appealing biomarkers to guide these surgical procedures; however, their utility is limited by the sparsity of electrode implantation as well as the normal confounds of spatiotemporally varying neural activity and connectivity. We propose that comparing intracranial EEG recordings to a normative atlas of intracranial EEG activity and connectivity can reliably map abnormal regions, identify targets for invasive treatment and increase our understanding of human epilepsy. Merging data from the Penn Epilepsy Center and a public database from the Montreal Neurological Institute, we aggregated interictal intracranial EEG retrospectively across 166 subjects comprising >5000 channels. For each channel, we calculated the normalized spectral power and coherence in each canonical frequency band. We constructed an intracranial EEG atlas by mapping the distribution of each feature across the brain and tested the atlas against data from novel patients by generating a z-score for each channel. We demonstrate that for seizure onset zones within the mesial temporal lobe, measures of connectivity abnormality provide greater distinguishing value than univariate measures of abnormal neural activity. We also find that patients with a longer diagnosis of epilepsy have greater abnormalities in connectivity. By integrating measures of both single-channel activity and inter-regional functional connectivity, we find a better accuracy in predicting the seizure onset zones versus normal brain (area under the curve = 0.77) compared with either group of features alone. We propose that aggregating normative intracranial EEG data across epilepsy centres into a normative atlas provides a rigorous, quantitative method to map epileptic networks and guide invasive therapy. We publicly share our data, infrastructure and methods, and propose an international framework for leveraging big data in surgical planning for refractory epilepsy.

A framework For brain atlases: Lessons from seizure dynamics.

Brain maps, or atlases, are essential tools for studying brain function and organization. The abundance of available atlases used across the neuroscience literature, however, creates an implicit challenge that may alter the hypotheses and predictions we make about neurological function and pathophysiology. Here, we demonstrate how parcellation scale, shape, anatomical coverage, and other atlas features may impact our prediction of the brain's function from its underlying structure. We show how network topology, structure-function correlation (SFC), and the power to test specific hypotheses about epilepsy pathophysiology may change as a result of atlas choice and atlas features. Through the lens of our disease system, we propose a general framework and algorithm for atlas selection. This framework aims to maximize the descriptive, explanatory, and predictive validity of an atlas. Broadly, our framework strives to provide empirical guidance to neuroscience research utilizing the various atlases published over the last century.

Developmental life stages of the Pickersgill's reed frog (Hyperolius pickersgilli) in an ex-situ environment at Johannesburg Zoo's captive breeding facility, South Africa.

Globally, the threats of habitat loss and disease on amphibian survival have necessitated the creation of ex-situ insurance populations as a conservation tool. We initiated a captive breeding project to create an insurance population for the endangered Pickersgill's reed frog (Hyperolius pickersgilli Raw, 1982) at the Johannesburg Zoo from parents collected from KwaZulu-Natal Province, South Africa, in 2017. We found that this species has seven developmental life stages, each with unique management requirements. The quiescent tadpoles hatched 6-8 days after the eggs were laid and remained at this stage for 2 days. The next stage, the developing tadpoles, showed no form of cannibalism or carrion feeding. The external appearance of the first leg (the right hind) occurred 5-6 weeks after the tadpoles hatched, and the metamorph stage was reached after 7-8 weeks. The metamorph stage lasted 3-5 days, after which tail resorption was complete and the froglet stage reached. Froglets could not be sexed externally, although body color changed based on the amount of light present at the resting place. Sub-adults were 6 months and older with adult coloration and sex differentiation visible even with color change. Adults were older than 18 months and fully developed and sexually mature, displaying amplexus, oviposition, and external fertilization. A greater understanding of Pickersgill's reed frog's developmental stages and physiological and environmental needs can improve captive breeding and subsequent release of the frogs, facilitate captive breeding elsewhere, and improve the species' conservation status.

A values-driven approach to vaccine hesitancy conversations.

South Africa recently experienced the third wave of the coronavirus disease 2019 (COVID-19)pandemic. Social media is flooded with polarised conversations, with opinions for and against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Many people are hesitant, and some are strongly opposed to vaccination. Vaccine hesitancy must be understood in historical, political and socio-cultural contexts. The aim of this study was to offer a values-driven approach to vaccine hesitancy conversations. It focusses on ethical dilemmas forthcoming from values violations, interrogating the personal and institutional scripts and rationalisations that prevent resolution, and offering ways of re-scripting these. Values-driven conversations provide safe spaces for vaccine-hesitant individuals to voice their reservations. The manner in which conversations are conducted is as important as the contents being discussed. Healthcare professionals are trusted by the public and should use ways of conversing that do not erode this trust. Creating respectful, compassionate platforms of engagement and incentivising vaccination are important measures for change in vaccine perspectives.

Simulated diagnostic performance of low-field MRI: Harnessing open-access datasets to evaluate novel devices.

The purpose of this study is to demonstrate a method for virtually evaluating novel imaging devices using machine learning and open-access datasets, here applied to a new, low-field strength portable 64mT MRI device. Paired 3 T and 64mT brain images were used to develop and validate a transformation converting standard clinical images to low-field quality images. Separately, 3 T images were aggregated from open-source databases spanning four neuropathologies: low-grade glioma (LGG, N = 76), high-grade glioma (HGG, N = 259), stroke (N = 28), and multiple sclerosis (MS, N = 20). The transformation method was then applied to the open-source data to generate simulated low-field images for each pathology. Convolutional neural networks (DenseNet-121) were trained to detect pathology in axial slices from either 3 T or simulated 64 mT images, and their relative performance was compared to characterize the potential diagnostic capabilities of low-field imaging. Algorithm performance was measured using area under the receiver operating characteristic curve. Across all cohorts, pathology detection was similar between 3 T and simulated 64mT images (LGG: 0.97 vs. 0.98; HGG: 0.96 vs. 0.95; stroke: 0.94 vs. 0.94; MS: 0.90 vs 0.87). Pathology detection was further characterized as a function of lesion size, intensity, and contrast. Simulated images showed decreasing sensitivity for lesions smaller than 4 cm2. While simulations cannot replace prospective trials during the evaluation of medical devices, they can provide guidance and justification for prospective studies. Simulated data derived from open-source imaging databases may facilitate testing and validation of new imaging devices.

Prognostic factors for recurrent idiopathic clubfoot deformity: a systematic literature review and meta-analysis.

Background and purpose - After initial clubfoot correction through Ponseti treatment, recurrence rates range from 26% to 48%. Even though various factors have been associated with increased recurrence risk, systematic assessments of the prognostic capacity of recurrence risk factors and their clinical relevance are lacking. Therefore we assessed clinically relevant prognostic factors for recurrent idiopathic clubfoot deformity after initial correction through Ponseti treatment. Methods - PubMed, Embase, Cinahl, and Web of Science were systematically searched for studies investigating the association between clinically relevant factors and recurrence rates. Prognostic factors were qualitatively assessed and included in the meta-analysis if ≥ 2 studies investigated the same factor and methods were comparable. Results - 34 articles were included in the qualitative synthesis, of which 22 were also included in the meta-analysis. Meta-analysis revealed that poor evertor muscle activity (OR = 255, 95% CI 30-2,190), brace non-compliance (OR = 10, CI 5-21), no additional stretching (OR = 31, CI 10-101), more casts (OR = 3.5, CI 1.6-7.8), lower education level of parents (OR = 1.8, CI 1.2-2.6), non-marital status of parents (OR = 1.8, CI 1.1-3.0), and higher Dimeglio scores (OR = 1.9, CI 1.2-3.3) were associated with higher recurrence rates. Interpretation - Brace non-compliance and poor evertor muscle activity have been identified as main recurrence risk factors and are therefore important to be closely monitored during clinical follow-up of clubfoot patients. Adding additional stretching during the bracing protocol might be promising in the quest to prevent relapse, but scientific evidence for clear clinical treatment recommendations is still limited.