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.

Diversity of Quaternary Structures Regulates Nuclear Receptor Activities.

Nuclear receptors (NRs) form homo- and/or heterodimers as central scaffolds of multiprotein complexes, which activate or repress gene transcription to regulate development, homeostasis, and metabolism. Recent studies on NR quaternary structure reveal novel mechanisms of receptor dimerization, the existence of tetrameric chromatin-bound NRs, and previously unanticipated protein-protein/protein-DNA interactions.

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.

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.

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.

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.

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.

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.

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.

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.

Observational evidence for interhemispheric hydroxyl-radical parity.

The hydroxyl radical (OH) is a key oxidant involved in the removal of air pollutants and greenhouse gases from the atmosphere. The ratio of Northern Hemispheric to Southern Hemispheric (NH/SH) OH concentration is important for our understanding of emission estimates of atmospheric species such as nitrogen oxides and methane. It remains poorly constrained, however, with a range of estimates from 0.85 to 1.4 (refs 4, 7-10). Here we determine the NH/SH ratio of OH with the help of methyl chloroform data (a proxy for OH concentrations) and an atmospheric transport model that accurately describes interhemispheric transport and modelled emissions. We find that for the years 2004-2011 the model predicts an annual mean NH-SH gradient of methyl chloroform that is a tight linear function of the modelled NH/SH ratio in annual mean OH. We estimate a NH/SH OH ratio of 0.97 ± 0.12 during this time period by optimizing global total emissions and mean OH abundance to fit methyl chloroform data from two surface-measurement networks and aircraft campaigns. Our findings suggest that top-down emission estimates of reactive species such as nitrogen oxides in key emitting countries in the NH that are based on a NH/SH OH ratio larger than 1 may be overestimated.

Modeling Water Quality in Watersheds: From Here to the Next Generation.

In this synthesis, we assess present research and anticipate future development needs in modeling water quality in watersheds. We first discuss areas of potential improvement in the representation of freshwater systems pertaining to water quality, including representation of environmental interfaces, in-stream water quality and process interactions, soil health and land management, and (peri-)urban areas. In addition, we provide insights into the contemporary challenges in the practices of watershed water quality modeling, including quality control of monitoring data, model parameterization and calibration, uncertainty management, scale mismatches, and provisioning of modeling tools. Finally, we make three recommendations to provide a path forward for improving watershed water quality modeling science, infrastructure, and practices. These include building stronger collaborations between experimentalists and modelers, bridging gaps between modelers and stakeholders, and cultivating and applying procedural knowledge to better govern and support water quality modeling processes within organizations.

Gratings for synchrotron and FEL beamlines: a project for the manufacture of ultra-precise gratings at Helmholtz Zentrum Berlin.

Blazed gratings are of dedicated interest for the monochromatization of synchrotron radiation when a high photon flux is required, such as, for example, in resonant inelastic X-ray scattering experiments or when the use of laminar gratings is excluded due to too high flux densities and expected damage, for example at free-electron laser beamlines. Their availability became a bottleneck since the decommissioning of the grating manufacture facility at Carl Zeiss in Oberkochen. To resolve this situation a new technological laboratory was established at the Helmholtz Zentrum Berlin, including instrumentation from Carl Zeiss. Besides the upgraded ZEISS equipment, an advanced grating production line has been developed, including a new ultra-precise ruling machine, ion etching technology as well as laser interference lithography. While the old ZEISS ruling machine GTM-6 allows ruling for a grating length up to 170 mm, the new GTM-24 will have the capacity for 600 mm (24 inch) gratings with groove densities between 50 lines mm-1 and 1200 lines mm-1. A new ion etching machine with a scanning radiofrequency excited ion beam (HF) source allows gratings to be etched into substrates of up to 500 mm length. For a final at-wavelength characterization, a new reflectometer at a new Optics beamline at the BESSY-II storage ring is under operation. This paper reports on the status of the grating fabrication, the measured quality of fabricated items by ex situ and in situ metrology, and future development goals.

Self-assembly and surface behaviour of pure and mixed zwitterionic amphiphiles in a deep eutectic solvent.

Recent investigations have shown that deep eutectic solvents provide a suitable environment for self-organisation of biomolecules, in particular phospholipids and proteins. However, the solvation of complex lyophilic moieties by deep eutectic solvents still remains unclear. Here we explore the behaviour of zwitterionic surfactants in choline chloride:glycerol eutectic mixture. Dodecyl-2-(trimethylammonio)ethylphosphate and N-alkyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (alkyl = dodecyl, tetradecyl) surfactants were investigated by means of surface tension, X-ray reflectivity and small-angle neutron scattering. These surfactants were found to remain surface active and form globular micelles in deep eutectic solvents. Still, the surface behaviour of these species was found to differ depending on the headgroup and tail structure. The morphology of the micelles also slightly varies between surfactants, demonstrating differences in the packing of individual monomers. The characteristics of mixtures of the dodecyl surfactants is also reported, showing a deviation from ideal mixing associated with attractive interactions between sulfobetaine and phosphocholine headgroups. Such non-ideality results in variation of the surface behaviour and self-assembly of these surfactant mixtures. The results presented here will potentially lead to the development of new alternatives for drug-delivery, protein solubilisation and biosensing through a better fundamental understanding of the behaviour of zwitterionic surfactants in deep eutectic solvents.

Counterion binding alters surfactant self-assembly in deep eutectic solvents.

Micellisation of surfactants in deep eutectic solvents has been recently demonstrated to provide a controllable way to modify micelle morphology. Ion-pair interactions between the solvent and the surfactant headgroup were identified as affecting the micellisation by modifying the charge density of the micelle. Here we explore the micellisation of dodecylsulfate surfactants with different counterions (Li+, Cs+, Mg2+, Bmim+, Emim+, cholinium+) dissolved in two deep eutectic solvents: choline chloride:urea and choline chloride:glycerol. Surface tension results show a solvent and counterion dependence of the CMC of the surfactants. Small-angle neutron scattering was subsequently used to investigate the morphology of the micelles formed. The results show that the elongation of the micelles is strongly dependent on the solvent, showing more elongated aggregates in choline chloride:urea than in choline chloride:glycerol. The morphology of micelles in DES was also found to depend on the counterion, where the affinity of binding showed similarities to that in water.

Identification and treatment of residual and relapsed idiopathic clubfoot in 88 children.

Background and purpose - The Ponseti treatment is successful in idiopathic clubfoot. However, approximately 11-48% of all clubfeet maintain residual deformities or relapse. Early treatment, which possibly reduces the necessity for additional surgery, requires early identification of these problematic clubfeet. We identify deformities of residual/relapsed clubfeet and the treatments applied to tackle these deformities in a large tertiary clubfoot treatment center. Patients and methods - Retrospective chart review of patients who visited our clinic between 2012 and 2015 focused on demographics, deformities of the residual/relapsed clubfoot, and applied treatment. Residual deformities were defined as deformities that were never fully corrected and needed additional treatment. We defined relapse as any deformity of the clubfoot reoccurring, after initial successful treatment, with necessity for additional treatment. Results - We identified 33 patients with residual and 55 patients with relapsed clubfeet. In both groups decreased dorsal flexion and adduction were the most often registered deformities. Furthermore, often equinus/decreased dorsiflexion, active supination, and varus occurred. In more than half, typical profiles of combined deformities were found. Relapses occurred at all stages of treatment and follow-up; half of the residual or relapsed clubfeet were identified before the end of the bracing period. In half of the patients, additional treatment consisted of the Ponseti treatment, one-quarter also required adaptation of the brace protocol, and one-quarter needed additional surgery. The Ponseti treatment was mainly reapplied if feet presented with relapses or residues until the age of 5. Interpretation - Practitioners should especially be aware of equinus/decreased dorsiflexion, adduction, and active supination as a sign of a residual or relapsed clubfoot. Due to the heterogeneous profiles of these clubfeet, treatment strategy should be based on a step-by step approach including recasting, bracing, and if necessary surgical intervention.

Should the Extended Lateral Approach Remain Part of Standard Treatment in Displaced Intra-articular Calcaneal Fractures?

The aim of this study was to evaluate the results of open reduction and internal fixation through the extended lateral approach (ELA) in displaced intra-articular calcaneal fractures and to determine whether this approach should remain part of standard therapy. This retrospective cohort study included 60 patients with 64 displaced intra-articular calcaneal fractures who underwent surgical treatment through the ELA. Outcome measures were the visual analog scale foot and ankle (VAS FA), the American Orthopedic Foot and Ankle Society (AOFAS) score, surgical site infections (SSIs), and reoperations. We determined the AOFAS score for 40 patients with 42 fractures, and 42 patients with 44 fractures completed the VAS FA questionnaire. The mean VAS FA score was 61.0 ± 23.4 and the median AOFAS score was 83 (range 33 to 100), with 55% good to excellent scores. We found 10.9% superficial SSIs successfully treated with antibiotics. In 4.7% of patients a deep SSI was diagnosed, wherefore premature implant removal was necessary. Patients with an SSI did not have significantly lower VAS FA or AOFAS scores than did patients without an SSI (p = .318 and p = .766, respectively). Implant removal in absence of SSIs was necessary in 17 patients because of pain, and 3 patients needed secondary arthrodesis because of persistent pain. We concluded that the ELA proved to be a safe procedure, and moreover the most common complications did not influence the long-term outcomes of patients. However, recent literature demonstrates that less invasive techniques seem to exceed the ELA with respect to wound complications.

Protein conformation in pure and hydrated deep eutectic solvents.

Deep eutectic solvents (DES) have recently been postulated as possible environments where protein structure may be preserved in the absence of water. Here we present our results towards understanding protein conformation in choline chloride-based DES and mixtures with water. Lysozyme and bovine serum albumin have been investigated by means of circular dichroism and small-angle neutron scattering.

Guideline on the diagnosis and treatment of primary idiopathic clubfoot.

- A delegation of 6 pediatric orthopedic surgeons from the Dutch Orthopedic Association (NOV) and 2 members of the board of the Dutch Parents' Association for children with clubfoot created the guideline "The diagnosis and treatment of primary idiopathic clubfeet" between April 2011 and February 2014. The development of the guideline was supported by a professional methodologist from the Dutch Knowledge Institute of Medical Specialists. This evidence-based guideline process was new and unique, in the sense that the process was initiated by a parents' association. This is the first official guideline in pediatric orthopedics in the Netherlands, and to our knowledge it is also the first evidence-based guideline on clubfoot worldwide. The guideline was developed in accordance with the criteria of the international AGREE instrument (AGREE II: Appraisal of Guidelines for Research and Evaluation II). The scientific literature was searched and systematically analyzed. In the second phase, conclusions and recommendations in the literature were formulated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Recommendations were developed considering the balance of benefits and harms, the type and quality of evidence, the values and preferences of the people involved, and the costs. The guideline is a solid foundation for standardization of clubfoot treatment in the Netherlands, with a clear recommendation of the Ponseti method as the optimal method of primary clubfoot treatment. We believe that the format used in the current guideline sets a unique example for guideline development in pediatric orthopedics that may be used worldwide. Our format ensured optimal collaboration between medical specialists and parents, and resulted in an important change in clubfoot care in the Netherlands, to the benefit of medical professionals as well as parents and patients. In this way, it is possible to improve professional collaboration between medical specialists and parents, resulting in an important change in clubfoot care in the Netherlands that will benefit medical professionals, parents, and patients. The guideline was published online, and is freely available from the Dutch Guideline Database ( www.richtlijnendatabase.nl ).

Micelle structure in a deep eutectic solvent: a small-angle scattering study.

In recent years many studies into green solvents have been undertaken and deep eutectic solvents (DES) have emerged as sustainable and green alternatives to conventional solvents since they may be formed from cheap non-toxic organic precursors. In this study we examine amphiphile behaviour in these novel media to test our understanding of amphiphile self-assembly within environments that have an intermediate polarity between polar and non-polar extremes. We have built on our recently published results to present a more detailed structural characterisation of micelles of sodium dodecylsulfate (SDS) within the eutectic mixture of choline chloride and urea. Here we show that SDS adopts an unusual cylindrical aggregate morphology, unlike that seen in water and other polar solvents. A new morphology transition to shorter aggregates was found with increasing concentration. The self-assembly of SDS was also investigated in the presence of water; which promotes the formation of shorter aggregates.