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.

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.

Magnetic resonance imaging measurement of placental perfusion and oxygen saturation in early-onset fetal growth restriction.

OBJECTIVE: We hypothesised that a multi-compartment magnetic resonance imaging (MRI) technique that is sensitive to fetal blood oxygenation would identify changes in placental blood volume and fetal blood oxygenation in pregnancies complicated by early-onset fetal growth restriction (FGR). DESIGN: Case-control study. SETTING: London, UK. POPULATION: Women with uncomplicated pregnancies (estimated fetal weight [EFW] >10th centile for gestational age [GA] and normal maternal and fetal Doppler ultrasound, n = 12) or early-onset FGR (EFW <3rd centile with or without abnormal Doppler ultrasound <32 weeks GA, n = 12) were studied. METHODS: All women underwent MRI examination. Using a multi-compartment MRI technique, we quantified fetal and maternal blood volume and feto-placental blood oxygenation. MAIN OUTCOME MEASURES: Disease severity was stratified according to Doppler pulsatility index and the relationship to the MRI parameters was investigated, including the influence of GA at scan. RESULTS: The FGR group (mean GA 27+5  weeks, range 24+2 to 33+6  weeks) had a significantly lower EFW compared with the control group (mean GA 29+1  weeks; -705 g, 95% CI -353 to -1057 g). MRI-derived feto-placental oxygen saturation was higher in controls compared with FGR (75 ± 9.6% versus 56 ± 16.2%, P = 0.02, 95% CI 7.8-30.3%). Feto-placental oxygen saturation estimation correlated strongly with GA at scan in controls (r = -0.83). CONCLUSION: Using a novel multimodal MRI protocol we demonstrated reduced feto-placental blood oxygen saturation in pregnancies complicated by early-onset FGR. The degree of abnormality correlated with disease severity defined by ultrasound Doppler findings. Gestational age-dependent changes in oxygen saturation were also present in normal pregnancies. TWEETABLE ABSTRACT: MRI reveals differences in feto-placental oxygen saturation between normal and FGR pregnancy that is associated with disease severity.

Automated versus subjective assessment of spatial and temporal MRI small bowel motility in Crohn's disease.

AIM: To investigate whether subjective radiologist grading of motility on magnetic resonance enterography (MRE) is as effective as software quantification, and to determine the combination of motility metrics with the strongest association with symptom severity. MATERIALS AND METHODS: One hundred and five Crohn's disease patients (52 male, 53 female, 16-68 years old, mean age 34 years old) recruited from two sites underwent MRE, including a 20 second breath-hold cine motility sequence. Each subject completed a Harvey-Bradshaw Index (HBI) symptom questionnaire. Five features within normally appearing bowel were scored visually by two experienced radiologists, and then quantified using automated analysis software, including (1) mean motility, (2) spatial motility variation, (3) temporal motility variation, (4) area of motile bowel, (5) intestinal distension. Multivariable linear regression derived the combination of features with the highest association with HBI score. RESULTS: The best automated metric combination was temporal variation (p<0.05) plus area of motile bowel (p<0.05), achieving an R2 adjusted value of 0.036. Spatial variation was also associated with symptoms (p<0.05, R2 adjusted = 0.034); however, when visually assessed by radiologists, none of the features had a significant relationship with the HBI score. CONCLUSION: Software quantified temporal and spatial variability in bowel motility are associated with abdominal symptoms in Crohn's disease. Subjective radiologist assessment of bowel motility is insufficient to detect aberrant motility. Automated analysis of motility patterns holds promise as an objective biomarker for aberrant physiology underlying symptoms in enteric disorders.

Multidisciplinary guidelines for the management of paediatric tracheostomy emergencies.

Temporary and permanent tracheostomies are required in children to manage actual or anticipated long-term ventilatory support, to aid secretion management or to manage fixed upper airway obstruction. Tracheostomies may be required from the first few moments of life, with the majority performed in children < 4 years of age. Although similarities with adult tracheostomies are apparent, there are key differences when managing the routine and emergency care of children with tracheostomies. The National Tracheostomy Safety Project identified the need for structured guidelines to aid multidisciplinary clinical decision making during paediatric tracheostomy emergencies. These guidelines describe the development of a bespoke emergency management algorithm and supporting resources. Our aim is to reduce the frequency, nature and severity of paediatric tracheostomy emergencies through preparation and education of staff, parents, carers and patients.

Bullseye's representation of cerebral white matter hyperintensities.

BACKGROUND AND PURPOSE: Visual rating scales have limited capacities to depict the regional distribution of cerebral white matter hyperintensities (WMH). We present a regional-zonal volumetric analysis alongside a visualization tool to compare and deconstruct visual rating scales. MATERIALS AND METHODS: 3D T1-weighted, T2-weighted spin-echo and FLAIR images were acquired on a 3T system, from 82 elderly participants in a population-based study. Images were automatically segmented for WMH. Lobar boundaries and distance to ventricular surface were used to define white matter regions. Regional-zonal WMH loads were displayed using bullseye plots. Four raters assessed all images applying three scales. Correlations between visual scales and regional WMH as well as inter and intra-rater variability were assessed. A multinomial ordinal regression model was used to predict scores based on regional volumes and global WMH burdens. RESULTS: On average, the bullseye plot depicted a right-left symmetry in the distribution and concentration of damage in the periventricular zone, especially in frontal regions. WMH loads correlated well with the average visual rating scores (e.g. Kendall's tau [Volume, Scheltens]=0.59 CI=[0.53 0.62]). Local correlations allowed comparison of loading patterns between scales and between raters. Regional measurements had more predictive power than global WMH burden (e.g. frontal caps prediction with local features: ICC=0.67 CI=[0.53 0.77], global volume=0.50 CI=[0.32 0.65], intra-rater=0.44 CI=[0.23 0.60]). CONCLUSION: Regional-zonal representation of WMH burden highlights similarities and differences between visual rating scales and raters. The bullseye infographic tool provides a simple visual representation of regional lesion load that can be used for rater calibration and training.

The role of mesoscopic structuring on the intermixing of spin-polarised conduction channels in thin-film ferromagnets for spintronics.

The separation of spin-up and spin-down conduction channels is fundamental to electronic transport in ferromagnets and essential for spintronic functionality. The spin states available for conduction are defined by the ferromagnetic material, but additional physical factors can affect scattering and modify the spin-dependence of conduction. Here the effect of mesoscopic structuring, arising during the growth of ferromagnetic thin films, on the electronic transport was investigated. Resistivity and anisotropic magnetoresistance were measured in a series of Ni80Fe20 thin films as a function of nominal film thickness from [Formula: see text] up to [Formula: see text]. The observed thickness dependence of the resisivity and magnetic anisotropy of resistivity are interpreted using a model that accounts for the macroscopic structuring from the growth of the films and incorporates a structural dependence of the spin-flip scattering. The model shows good agreement for both the thickness dependence of the resistivity and the reduction of the anisotropic magnetoresistivity. The latter indicating that increasing mixing of the conducting spin channels occurs in ultra-thin films, mainly a consequence of macroscopic structuring of the films.

Impact of a peri-operative quality improvement programme on postoperative pulmonary complications.

Postoperative pulmonary complications are common, with a reported incidence of 2-40%, and are associated with adverse outcomes that include death, longer hospital stay and reduced long-term survival. Enhanced recovery is now a standard of care for patients undergoing elective major surgery. Despite the high prevalence of pulmonary complications in this population, few elements of enhanced recovery specifically address reducing these complications. In 2013, a prevalence audit confirmed a postoperative pulmonary complication rate of 16/83 (19.3%) in patients undergoing elective major surgery who were admitted to critical care postoperatively. A quality improvement team developed and implemented ERAS+, an innovative model of peri-operative care combining elements of enhanced recovery with specific measures aimed at reducing pulmonary complications. ERAS+ was introduced in June 2014, with full implementation in September 2014. Patients were screened during full ERAS+ implementation and again one year following implementation. Following ERAS+ implementation, postoperative pulmonary complications reduced to 24/228 (10.5%). Sustained improvement was evident one year after implementation, with a pulmonary complication rate of 16/183 (8.7%). Median (IQR [range]) length of hospital stay one year after implementation of ERAS+ also improved from 12 (9-15 [4-101]) to 9 (5.5-10.5 [3-81]) days. The ERAS+ pathway is applicable to patients undergoing elective major surgery and appears effective in reducing postoperative pulmonary complications.

Benchmarking passive transfer of immunity and growth in dairy calves.

Poor health and growth in young dairy calves can have lasting effects on their development and future production. This study benchmarked calf-rearing outcomes in a cohort of Canadian dairy farms, reported these findings back to producers and their veterinarians, and documented the results. A total of 18 Holstein dairy farms were recruited, all in British Columbia. Blood samples were collected from calves aged 1 to 7 d. We estimated serum total protein levels using digital refractometry, and failure of passive transfer (FPT) was defined as values below 5.2 g/dL. We estimated average daily gain (ADG) for preweaned heifers (1 to 70 d old) using heart-girth tape measurements, and analyzed early (≤35 d) and late (>35 d) growth separately. At first assessment, the average farm FPT rate was 16%. Overall, ADG was 0.68 kg/d, with early and late growth rates of 0.51 and 0.90 kg/d, respectively. Following delivery of the benchmark reports, all participants volunteered to undergo a second assessment. The majority (83%) made at least 1 change in their colostrum-management or milk-feeding practices, including increased colostrum at first feeding, reduced time to first colostrum, and increased initial and maximum daily milk allowances. The farms that made these changes experienced improved outcomes. On the 11 farms that made changes to improve colostrum feeding, the rate of FPT declined from 21 ± 10% before benchmarking to 11 ± 10% after making the changes. On the 10 farms that made changes to improve calf growth, ADG improved from 0.66 ± 0.09 kg/d before benchmarking to 0.72 ± 0.08 kg/d after making the management changes. Increases in ADG were greatest in the early milk-feeding period, averaging 0.13 kg/d higher than pre-benchmarking values for calves ≤35 d of age. Benchmarking specific outcomes associated with calf rearing can motivate producer engagement in calf care, leading to improved outcomes for calves on farms that apply relevant management changes.

The KICA Carer: informant information to enhance the Kimberley Indigenous Cognitive Assessment.

BACKGROUND: A quality dementia-screening tool is required for older remote Aboriginal Australians who have high rates of dementia and limited access to appropriate medical equipment and clinicians. The Kimberley Indigenous Cognitive Assessment (KICA Cog) is a valid cognitive test for dementia in Aboriginal and Torres Strait Islander peoples. The KICA cognitive informant questionnaire (KICA Carer) had yet to be analyzed to determine validity alone or in combination with the KICA Cog. METHODS: The KICA Carer was completed by nominated informants of 349 remote-living Aboriginal Australians in the Kimberley region, Western Australia. Validity was assessed by comparing KICA Carer with Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and International Classification of Diseases (ICD-10) consensus diagnoses based on a blinded specialist review. KICA Carer and KICA Cog were then compared to determine joint validity. RESULTS: A KICA Carer score of ≥3/16 gave optimum sensitivity (76.2%) and specificity (81.4%), area under curve (AUC) 0.89 (95% CI = 0.85, 0.94) with positive predictive value (PPV) of 35.8%, and negative predictive value (NPV) of 96.2%. A KICA Cog score of ≤33/39 gave a sensitivity of 92.9% and specificity of 89.9%, AUC 0.96 (95% CI = 0.94, 0.98), with PPV of 55.6% and NPV of 98.9%. Cut-off scores of KICA Cog ≤ 33/39 and KICA Carer ≥ 2/16 in series indicate possible dementia, with sensitivity of 90.5% and specificity of 93.5%. In this setting, PPV was 66.5% and NPV was 98.6%. CONCLUSIONS: The KICA Carer is an important tool to accurately screen dementia in remote Aboriginal Australians when the KICA Cog is unable to be used for a patient. It is readily accepted by caregivers. KEY POINTS: • For the best practice in the cognitive assessment of an Aboriginal Australian aged over 45 years, KICA Cog should be utilized. • In cases where Aboriginal patients are not assessed directly, KICA Carer should be conducted with an informant. A cut-off score of ≥3/16 should be used (these tools can be downloaded from www.wacha.org.au/kica.html).

Interfacial Structure Dependent Spin Mixing Conductance in Cobalt Thin Films.

Enhancement of Gilbert damping in polycrystalline cobalt thin-film multilayers of various thicknesses, overlayered with copper or iridium, was studied in order to understand the role of local interface structure in spin pumping. X-ray diffraction indicates that cobalt films less than 6 nm thick have strong fcc(111) texture while thicker films are dominated by hcp(0001) structure. The intrinsic damping for cobalt thicknesses above 6 nm is weakly dependent on cobalt thickness for both overlayer materials, and below 6 nm the iridium overlayers show higher damping enhancement compared to copper overlayers, as expected due to spin pumping. The interfacial spin mixing conductance is significantly enhanced in structures where both cobalt and iridium have fcc(111) structure in comparison to those where the cobalt layer has subtly different hcp(0001) texture at the interface.

Cardiopulmonary exercise testing and survival after elective abdominal aortic aneurysm repair†.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is increasingly used in the preoperative assessment of patients undergoing major surgery. The objective of this study was to investigate whether CPET can identify patients at risk of reduced survival after abdominal aortic aneurysm (AAA) repair. METHODS: Prospectively collected data from consecutive patients who underwent CPET before elective open or endovascular AAA repair  (EVAR) at two tertiary vascular centres between January 2007 and October 2012 were analysed. A symptom-limited maximal CPET was performed on each patient. Multivariable Cox proportional hazards regression modelling was used to identify risk factors associated with reduced survival. RESULTS: The study included 506 patients with a mean age of 73.4 (range 44-90). The majority (82.6%) were men and most (64.6%) underwent EVAR. The in-hospital mortality was 2.6%. The median follow-up was 26 months. The 3-year survival for patients with zero or one sub-threshold CPET value ([Formula: see text] at AT<10.2 ml kg(-1) min(-1), peak [Formula: see text]<15 ml kg(-1) min(-1) or [Formula: see text] at AT>42) was 86.4% compared with 59.9% for patients with three sub-threshold CPET values. Risk factors independently associated with survival were female sex [hazard ratio (HR)=0.44, 95% confidence interval (CI) 0.22-0.85, P=0.015], diabetes (HR=1.95, 95% CI 1.04-3.69, P=0.039), preoperative statins (HR=0.58, 95% CI 0.38-0.90, P=0.016), haemoglobin g dl(-1) (HR=0.84, 95% CI 0.74-0.95, P=0.006), peak [Formula: see text]<15 ml kg(-1) min(-1) (HR=1.63, 95% CI 1.01-2.63, P=0.046), and [Formula: see text] at AT>42 (HR=1.68, 95% CI 1.00-2.80, P=0.049). CONCLUSIONS: CPET variables are independent predictors of reduced survival after elective AAA repair and can identify a cohort of patients with reduced survival at 3 years post-procedure. CPET is a potentially useful adjunct for clinical decision-making in patients with AAA.

Efficacy of liposome-encapsulated ciprofloxacin in a murine model of Q fever.

Encapsulation of antibiotics may improve treatment of intracellular infections by prolonging antibiotic release and improving antibiotic uptake into cells. In this study, liposome-encapsulated ciprofloxacin for inhalation (CFI) was evaluated as a postexposure therapeutic for the treatment of Coxiella burnetii, the causative agent of Q fever. Intranasal treatment of male A/Jola (A/J) mice with CFI (50 mg/kg of body weight) once daily for 7 days protected mice against weight loss and clinical signs following an aerosol challenge with C. burnetii. In comparison, mice treated twice daily with oral ciprofloxacin or doxycycline (50 mg/kg) or phosphate-buffered saline (PBS) lost 15 to 20% body weight and exhibited ruffled fur, arched backs, and dehydration. Mice were culled at day 14 postchallenge. The weights and bacterial burdens of organs were determined. Mice treated with CFI exhibited reduced splenomegaly and reduced bacterial numbers in the lungs and spleen compared to mice treated with oral ciprofloxacin or doxycycline. When a single dose of CFI was administered, it provided better protection against body weight loss than 7 days of treatment with oral doxycycline, the current antibiotic of choice to treat Q fever. These data suggest that CFI has potential as a superior antibiotic to treat Q fever.

Cardiopulmonary exercise testing for preoperative risk assessment before pancreaticoduodenectomy for cancer.

OBJECTIVE: Pancreaticoduodenectomy is the standard of care for tumors confined to the head of pancreas and can be undertaken with low operative mortality. The procedure has a high morbidity, particularly in older patient populations with preexisting comorbidities. This study evaluated the role of cardiopulmonary exercise testing to predict postoperative morbidity and outcome in high-risk patients undergoing pancreaticoduodenectomy. METHODS: In a prospective cohort of consecutive patients undergoing pancreaticoduodenectomy, those aged over 65 years (or younger with comorbidity) were categorized as high risk and underwent preoperative assessment by cardiopulmonary exercise testing (CPET) according to a predefined protocol. Data were collected on functional status, postoperative complications, and survival. RESULTS: A total of 143 patients underwent preoperative assessment, 50 of whom were deemed to be at low risk for surgery per study protocol. Of 93 high-risk patients, 64 proceeded to surgery after preoperative CPET. Neither anaerobic threshold (AT) nor maximal oxygen consumption ([Formula: see text] O 2 MAX) predicted patient mortality or morbidity. However, ventilatory equivalent of carbon dioxide ([Formula: see text] E/[Formula: see text] CO 2) at AT was a predictive marker of postoperative mortality, with an area under the curve (AUC) of 0.84 (95 % confidence interval [CI] 0.63-1.00, p = 0.020); a threshold of 41 was 75 % sensitive and 95 % specific (positive predictive value 50 %, negative predictive value 98 %). Above this threshold, raised [Formula: see text] E/[Formula: see text] CO 2 predicted poor long-term survival (hazard ratio 2.05, 95 % CI 1.09-3.86, p = 0.026). CONCLUSIONS: CPET is a useful adjunctive test for predicting postoperative outcome in patients being assessed for pancreaticoduodenectomy. Raised CPET-derived [Formula: see text] E/[Formula: see text] CO 2 predicts early postoperative death and poor long-term survival.

Variability in disease burden and management of rheumatic fever and rheumatic heart disease in two regions of tropical Australia.

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) contribute to Aboriginal Australian and Torres Strait Islander health disadvantage. At the time of this study, specialist ARF/RHD care in the Kimberley region of Western Australia was delivered by a broad range of providers. In contrast, in Far North Queensland (FNQ), a single-provider model was used as part of a coordinated RHD control programme. AIMS: To review ARF/RHD management in the Kimberley and FNQ to ascertain whether differing models of service delivery are associated with different disease burden and patient care. METHODS: An audit of ARF/RHD management. Classification and clinical management data were abstracted from health records, specialist letters, echocardiograms and regional registers using a standardised data collection tool. RESULTS: Four hundred and seven patients were identified, with 99% being Aboriginal and/or Torres Strait Islanders. ARF without RHD was seen in 0.4% of Aboriginal and/or Torres Strait Islander residents and RHD in 1.1%. The prevalence of RHD was similar in both regions but with more severe disease in the Kimberley. More FNQ RHD patients had specialist review within recommended time frames (67% vs 45%, χ(2) , P < 0.001). Of patients recommended benzathine penicillin secondary prophylaxis, 17.7% received ≥80% of scheduled doses in the preceding 12 months. Prescription and delivery of secondary prophylaxis was greater in FNQ. CONCLUSIONS: FNQ's single-provider model of specialist care and centralised RHD control programme were associated with improved patient care and may partly account for the fewer cases of severe disease and reduced surgical procedures and other interventions observed in this region.

Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.

Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.

Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity.

Cardiac arrhythmias cause sudden death in 300,000 United States citizens every year. In this study, we describe two new loci for an inherited cardiac arrhythmia, long QT syndrome (LQT). In 1991 we reported linkage of LQT to chromosome 11p15.5. In this study we demonstrate further linkage to D7S483 in nine families with a combined lod score of 19.41 and to D3S1100 in three families with a combined score of 6.72. These findings localize major LQT genes to chromosomes 7q35-36 and 3p21-24, respectively. Linkage to any known locus was excluded in three families indicating that additional heterogeneity exists. Proteins encoded by different LQT genes may interact to modulate cardiac repolarization and arrhythmia risk.

Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.

Genetic factors contribute to the risk of sudden death from cardiac arrhythmias. Here, positional cloning methods establish KVLQT1 as the chromosome 11-linked LQT1 gene responsible for the most common inherited cardiac arrhythmia. KVLQT1 is strongly expressed in the heart and encodes a protein with structural features of a voltage-gated potassium channel. KVLQT1 mutations are present in affected members of 16 arrhythmia families, including one intragenic deletion and ten different missense mutations. These data define KVLQT1 as a novel cardiac potassium channel gene and show that mutations in this gene cause susceptibility to ventricular tachyarrhythmias and sudden death.

Dental enamel defects and dental caries of primary teeth among Indigenous children in Western Australia.

BACKGROUND: Teeth affected with enamel defects (EDs) are at an increased risk of dental caries. In spite of improving oral health status overall in Australia, Indigenous Australians still experience higher rates of dental caries than non-Indigenous Australians. This study reports on the prevalence of EDs and dental caries experience among Indigenous children in the Kimberley region of Western Australia. METHODS: Health status of all the primary teeth (ICDAS II criteria) and the presence of EDs on index teeth (modified Dental Defects of Enamel index; DDE) of young Indigenous children who participated in a 2-arm intervention trial was recorded. Generalized estimating equations were used to estimate the association between EDs and dental caries and effect estimates were presented as odds ratios and associated 95% confidence intervals. RESULTS: Person-level prevalence, from 237 children (mean age 3.6 years, standard deviation 1.7) assessed for EDs, was 58% and tooth-level prevalence was 24%. Teeth affected with demarcated or diffuse defects were associated with a twofold higher odds of having caries experience, odds ratio (OR) 2.5, 95% confidence interval (CI) 1.7-3.7 and OR 2.7, 95% CI 1.7-4.0 respectively. CONCLUSIONS: The presence of EDs among young Indigenous children was associated with a higher odds of caries experience among affected teeth.