Proof-of-Principle Experiment on the Dynamic Shell Formation for Inertial Confinement Fusion.

In the dynamic-shell (DS) concept [V. N. Goncharov et al., Novel Hot-Spot Ignition Designs for Inertial Confinement Fusion with Liquid-Deuterium-Tritium Spheres, Phys. Rev. Lett. 125, 065001 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.065001] for laser-driven inertial confinement fusion the deuterium-tritium fuel is initially in the form of a homogeneous liquid inside a wetted-foam spherical shell. This fuel is ignited using a conventional implosion, which is preceded by a initial compression of the fuel followed by its expansion and dynamic formation of a high-density fuel shell with a low-density interior. This Letter reports on a scaled-down, proof-of-principle experiment on the OMEGA laser demonstrating, for the first time, the feasibility of DS formation. A shell is formed by convergent shocks launched by laser pulses at the edge of a plasma sphere, with the plasma itself formed as a result of laser-driven compression and relaxation of a surrogate plastic-foam ball target. Three x-ray diagnostics, namely, 1D spatially resolved self-emission streaked imaging, 2D self-emission framed imaging, and backlighting radiography, have shown good agreement with the predicted evolution of the DS and its stability to low Legendre mode perturbations introduced by laser irradiation and target asymmetries.

High-resolution x-ray spectrometer for x-ray absorption fine structure spectroscopy.

Two extended x-ray absorption fine structure flat crystal x-ray spectrometers (EFX's) were designed and built for high-resolution x-ray spectroscopy over a large energy range with flexible, on-shot energy dispersion calibration capabilities. The EFX uses a flat silicon [111] crystal in the reflection geometry as the energy dispersive optic covering the energy range of 6.3-11.4 keV and achieving a spectral resolution of 4.5 eV with a source size of 50 µm at 7.2 keV. A shot-to-shot configurable calibration filter pack and Bayesian inference routine were used to constrain the energy dispersion relation to within ±3 eV. The EFX was primarily designed for x-ray absorption fine structure (XAFS) spectroscopy and provides significant improvement to the Laboratory for Laser Energetics' OMEGA-60 XAFS experimental platform. The EFX is capable of performing extended XAFS measurements of multiple absorption edges simultaneously on metal alloys and x-ray absorption near-edge spectroscopy to measure the electron structure of compressed 3d transition metals.

Achalasia cardia: A five-year review in Hospital Tuanku Ja'afar, Seremban.

INTRODUCTION: Achalasia cardia is an oesophageal motility disorder that affects various age groups. This study focused on the epidemiological features of achalasia, its risk factors, treatment modalities offered and the clinical outcomes in a tertiary hospital. MATERIALS AND METHODS: A retrospective search was carried out on all patients with a diagnosis of achalasia cardia in Hospital Tuanku Ja'afar (HTJ), Seremban, Malaysia between 2014 and 2018. Demographic data, patient symptomatology, and definitive management options were determined from the records. Telephone interviews were conducted to evaluate patient satisfaction with the outcome of treatment. RESULTS: There were 30 patients with a newly diagnosed achalasia cardia in that 5-year period, with an equal incidence among men and women. The mean age of presentation was 44.63 ± 18.21 years. Malays formed the largest group. The mean weight and body mass index were 46.8 ± 10.4 kg and 18.0 ± 4.4 kg/m2 respectively. There was a wide range of duration of symptoms at presentation with a mean of 30.11 ± 35.29 months. Almost all patients presented with dysphagia (96.7%) while 70% also noted loss of weight. All patients underwent oesophagogastroduodenoscopy (OGDS) and 26 patients (86.7%) had barium swallow as part of diagnostic workup. A total of 18 patients underwent a laparoscopic Heller myotomy with or without Dor Fundoplication and/or cruroplasty while two patients (6.7%) underwent pneumatic dilatation as first treatment. Iatrogenic mucosal perforations were detected in 8 patients who underwent myotomy and fundoplication and were repaired intraoperatively. Of the patients who underwent myotomy and fundoplication, the mean weight increase was 15.6kg, increasing from 43.0 ± 8.4 kg to 58.6 ± 13.7 kg. All the patients who underwent treatment were satisfied with their treatment outcomes. CONCLUSION: Most patients with achalasia cardia deemed suitable for surgery and counselled accordingly accept surgery resulting in high levels of satisfaction and weight gain in almost all these patients. A small minority who opt for pneumatic dilatation may also achieve satisfactory outcomes comparable to surgery in the short term. Although rare, clinicians should be able to recognise this disease early as early intervention often leads to satisfactory longterm outcomes.

Constraining physical models at gigabar pressures.

High-energy-density (HED) experiments in convergent geometry are able to test physical models at pressures beyond hundreds of millions of atmospheres. The measurements from these experiments are generally highly integrated and require unique analysis techniques to procure quantitative information. This work describes a methodology to constrain the physics in convergent HED experiments by adapting the methods common to many other fields of physics. As an example, a mechanical model of an imploding shell is constrained by data from a thin-shelled direct-drive exploding-pusher experiment on the OMEGA laser system using Bayesian inference, resulting in the reconstruction of the shell dynamics and energy transfer during the implosion. The model is tested by analyzing synthetic data from a one-dimensional hydrodynamics code and is sampled using a Markov chain Monte Carlo to generate the posterior distributions of the model parameters. The goal of this work is to demonstrate a general methodology that can be used to draw conclusions from a wide variety of HED experiments.

Energy Flow in Thin Shell Implosions and Explosions.

Energy flow and balance in convergent systems beyond petapascal energy densities controls the fate of late-stage stars and the potential for controlling thermonuclear inertial fusion ignition. Time-resolved x-ray self-emission imaging combined with a Bayesian inference analysis is used to describe the energy flow and the potential information stored in the rebounding spherical shock at 0.22 PPa (2.2 Gbar or billions of atmospheres pressure). This analysis, together with a simple mechanical model, describes the trajectory of the shell and the time history of the pressure at the fuel-shell interface, ablation pressure, and energy partitioning including kinetic energy of the shell and internal energy of the fuel. The techniques used here provide a fully self-consistent uncertainty analysis of integrated implosion data, a thermodynamic-path independent measurement of pressure in the petapascal range, and can be used to deduce the energy flow in a wide variety of implosion systems to petapascal energy densities.

Modelling the potential impact of adherence technologies on tuberculosis in India.

BACKGROUND: For patients taking standard first-line tuberculosis treatment, missing 10% or more of their doses increases the risk of relapse six-fold. Digital technologies offer new approaches to adherence support for TB patients. We estimated the potential impact of new adherence technologies in India.METHOD: We developed a mathematical model of TB transmission dynamics in India, capturing the independent effects of missed doses and treatment default on post-treatment recurrence. We simulated the impact of interventions to address both missed doses and treatment default in the public and private healthcare sector.RESULTS: Adherence interventions, if deployed optimally in the public sector alone, would reduce cumulative TB incidence by 7.3% (95% credible intervals [CrI] 4.7-11) between 2020 and 2030, and by 16% (95% CrI 11-23) if also deployed in the private sector. This impact is roughly proportional to the effectiveness of the interventions. Reducing missed doses reduced incidence by 12% (95% CrI 7.0-18), while reducing treatment default reduced incidence by 7.9% (95% CrI 3.2-13).CONCLUSION: Minimising missed doses is at least as important as promoting treatment completion. Our results suggest that emerging technologies to improve treatment adherence could have a substantial impact on TB incidence and mortality in India.

Knowledge, attitude and practice towards dietary iron among patients with thalassemia and their caregivers in Peninsular Malaysia.

INTRODUCTION: Thalassemias are the most common human monogenic disorders in the world. Regular blood transfusion and increased intestinal absorption of iron among thalassemia patients will lead to iron overload, which will not only markedly decrease their life expectancy but also pose a heavy burden to the healthcare system. The objective of this study was to evaluate the level of knowledge, attitude and practice towards dietary iron among thalassemia patients and their caregivers. METHODS: An analytical cross-sectional study using purposive sampling method was conducted at eight thalassemia societies in Peninsular Malaysia. 260 respondents comprised of patients and caregivers were assessed with two separate sets of questionnaires. RESULTS: Knowledge on dietary iron among the respondents was unsatisfactory, despite them having good knowledge on thalassemia disorder. Female patients were found to have better dietary knowledge, attitude and practice compared to males. The percentage of caregivers with good attitude and good practice were significantly higher compared to adult patients. Caregivers with children on iron chelators were noted to have better dietary attitude and practice. Thalassemia knowledge and children on vitamins were found to be the predictors of dietary knowledge among the patients and caregivers respectively. CONCLUSION: The level of knowledge on dietary iron among the patients and caregivers was unsatisfactory in spite of their attitude and practice towards dietary iron were good. Effective delivery of dietary information to the patients and caregivers is essential to enable them to choose a healthy diet for their condition.

Transnasal frontal intersinus septum takedown for frontal sinus pyocele.

INTRODUCTION: The open frontal intersinus septum takedown (FISST) technique was first described in 1976. We describe our experience with an endoscopic transnasal approach to manage a frontal sinus pyocele arising from an obstructed frontal sinus outflow tract due to anterolateral thigh flap reconstruction of a maxillectomy defect. CASE REPORT: A 40-year-old lady experienced upper eyelid swelling and purulent nasal discharge 3 weeks after undergoing a left extended medial maxillectomy with free anterolateral thigh flap reconstruction. A computed tomography (CT) scan revealed total opacification of the left frontal sinus. There was no improvement with intravenous antibiotics and she underwent a surgery, whenshe was found intraoperatively to have a frontal sinus pyocele, which was then drained. She then underwent an endoscopic transnasal FISST to ventilate the left frontal sinus via the contralateral frontal recess with good results. A CT scan performed 3 months postoperatively showed a widely patent interfrontal sinus septal window and right frontal outflow tract with no disease recurrence. DISCUSSION: The FISST is a useful technique to manage unilateral frontal sinus disease by taking advantage of the contralateral outflow tract when the ipsilateral frontal recess is obstructed.

Rhinogenous optic neuritis with full recovery of vision - The role of endoscopic optic nerve decompression and a review of literature.

BACKGROUND: Optic neuritis resulting from paranasal sinusitis is an infrequently described but clinically important and treatable entity. The role of optic nerve decompression has been well established in atraumatic optic neuropathies which are compressive in origin. However, its role in optic neuritis and other infective or inflammatory processes is lacking, and the role for early surgical intervention remains controversial. CASE REPORT: In this case report, we describe a patient who presented with sudden onset of right vision loss secondary to optic neuritis from pansinusitis. He was treated with systemic antibiotics and steroids along with an urgent endoscopic sinus surgery with optic nerve decompression. Full restoration of his vision was recorded within 24 h of surgical decompression. CONCLUSION: Optic neuritis secondary to paranasal sinusitis is a clinically important entity and timely diagnosis and decompression is key to vision restoration.

Mating strategies to maximize genetic merit in dairy cattle herds.

The genetic merit of a herd is a key determinant in productivity for dairy farmers. However, making breeding decisions to maximize the rate of genetic gain can be complex because there is no certainty about which cows will become pregnant with a heifer calf. In this study, breeding worth (BrW) was used as a measure of genetic merit, and several mating strategies were evaluated. These strategies included randomly mating whole herds to the entire bull team, excluding low-ranked cows from producing replacement heifers, and nominating high-ranked cows to the most highly ranked bulls. Simulations were undertaken using 4 bull teams generated from bulls currently marketed in New Zealand and a selection of New Zealand dairy herds. Average replacement heifer BrW was calculated for 1,000 iterations of each combination of mating strategy, herd, and bull team (scenario). Variation in resulting average replacement heifer BrW within scenarios was due to random sampling of which cows became pregnant with a heifer calf. Relative to mating the whole herd to an entire bull team, excluding the lowest ranked cows from producing replacements resulted in the greatest increase in average replacement heifer BrW across all herds and bull teams, with a gain of approximately 0.4 BrW point for each 1% of cows excluded. Nominating top-ranking cows to the highest ranking bulls in the team had little effect (0.06-0.13 BrW increase for each 1% of top cows nominated) in improving BrW of replacement heifers. The number of top bulls nominated had a variable effect depending on the BrW spread of the entire bull team. Although excluding cows with the lowest BrW from producing replacement heifers is most effective for improving BrW, it is important to ensure that the number of heifers born is sufficient to replace cows leaving the herd. It is likely that optimal strategies for improving BrW will vary from farm to farm depending not only on the BrW structure of the herd, the bull team available, and the reproduction success on farm but also on farm management practices. This simulation study provides expected outcomes from a variety of mating strategies to allow informed decision making on farm.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies.

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices.

Market assessment of tuberculosis diagnostics in China in 2012.

OBJECTIVE: To assess the 2012 served available market for tuberculosis (TB) diagnostics in China in the sector served by the China Centre for Disease Control and Prevention (CDC) and the hospital sector in China, including both designated TB hospitals and general hospitals. DESIGN: Test volumes and unit costs were assessed for tuberculin skin tests, interferon-gamma release assays (IGRAs), smear microscopy, serology, cultures, speciation tests, nucleic-acid amplification tests (NAATs), drug susceptibility tests and adenosine-deaminase tests (ADA). Data were obtained from electronic databases (CDC sector) and through surveys (hospital sector), and were estimated for the two sectors and for the country as a whole. Test costs were estimated by staff at China CDC, and using published literature. RESULTS: In 2012, the China CDC and hospital sectors performed a total of 44 million TB diagnostic tests at an overall value of US$294 million. Tests used by the CDC sector were smear microscopy, solid and liquid culture and DST, while the hospital sector also used IGRAs, NAATs, ADA and serology. The hospital sector accounted for 76% of the overall test volume and 94% of the market value. CONCLUSION: China has a very large TB diagnostic market that encompasses a wide range of diagnostic tests, with the majority being performed in Chinese hospitals.

The affordability for patients of a new universal MDR-TB coverage model in China.

BACKGROUND: China has piloted a new model of universal coverage for multidrug-resistant tuberculosis (MDR-TB), designed to rationalize hospital use of drugs and tests and move away from fee-for-service payment towards a standard package with financial protection against catastrophic health costs. OBJECTIVE: To evaluate the affordability to patients of this new model. DESIGN: This was an observational study of 243 MDR-TB cases eligible for enrolment on treatment under the project. We assessed the affordability of the project from the perspective of households, with a focus on catastrophic costs. RESULTS: Of the 243 eligible cases, 172 (71%) were enrolled on treatment; of the 71 cases not enrolled, 26 (37%) cited economic reasons. The 73 surveyed cases paid an average of RMB 5977 (US$920) out-of-pocket in search costs incurred outside the pilot model. Within the pilot, they paid another RMB 2094 (US$322) in medical fees and RMB 5230 (US$805) in direct non-medical costs. Despite 90% reimbursement of medical fees, 78% of households experienced catastrophic costs, including indirect costs. CONCLUSION: The objectives of the pilot model are aligned with health reform in China and universal health coverage globally. Enrollment would almost certainly be higher with 100% reimbursement of medical fees, but patient enablers will be required to truly eliminate catastrophic costs.

RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity.

RUNX1/AML1 is among the most commonly mutated genes in human leukemia. Haploinsufficiency of RUNX1 causes familial platelet disorder with predisposition to myeloid malignancies (FPD/MM). However, the molecular mechanism of FPD/MM remains unknown. Here we show that murine Runx1(+/-) hematopoietic cells are hypersensitive to granulocyte colony-stimulating factor (G-CSF), leading to enhanced expansion and mobilization of stem/progenitor cells and myeloid differentiation block. Upon G-CSF stimulation, Runx1(+/-) cells exhibited a more pronounced phosphorylation of STAT3 as compared with Runx1(+/+) cells, which may be due to reduced expression of Pias3, a key negative regulator of STAT3 signaling, and reduced physical sequestration of STAT3 by RUNX1. Most importantly, blood cells from a FPD patient with RUNX1 mutation exhibited similar G-CSF hypersensitivity. Taken together, Runx1 haploinsufficiency appears to predispose FPD patients to MM by expanding the pool of stem/progenitor cells and blocking myeloid differentiation in response to G-CSF.

Emergence of Zika Virus Epidemic and the National Response in Jamaica.

BACKGROUND: Jamaica, along with the Americas, experienced major epidemics of arboviral diseases transmitted by the Aedes aegypti mosquito in recent years. These include dengue fever in 2012, Chikungunya fever in 2014 and Zika virus infection (ZIKV) in 2016. We present the emergence of the ZIKV epidemic in Jamaica and outline the national response. METHODS: The Ministry of Health's preparedness included: heightened surveillance, clinical management guidance, vector control and management, laboratory capacity strengthening, training and staffing, risk communication and public education, social mobilization, inter-sectoral collaboration, resource mobilization and international cooperation. RESULTS: The first case of ZIKV was confirmed on January 29, 2016 with date of onset of January 17, 2016. From January 3 to July 30, 2016 (Epidemiological Week (EW) 1-30), 4648 cases of ZIKV were recorded (4576 suspected, 72 laboratory-confirmed). Leading symptoms were similar among suspected and confirmed cases: rash (71% and 88%), fever (65% and 53%) and joint pains (47% and 38%). There were 17 suspected cases of Guillain Barre syndrome; 383 were reported in pregnant women, with no reports of microcephaly to date. Zika and dengue viruses were circulating predominantly in 2016. At EW30, 1744 cases of dengue were recorded (1661 suspected and 83 confirmed). Dengue serotypes 3 and 4 were circulating with 121 reports of dengue haemorrhagic fever. CONCLUSION: The possibility exists for endemicity of ZIKV similar to dengue and chikungunya in Jamaica. A ZIKV vaccine, similar to the dengue and chikungunya vaccines, is needed to be fast-tracked into clinical trials to mitigate the effects of this disease.

Emergence of zika virus epidemic and the national response in Jamaica

BACKGROUND: Jamaica, along with the Americas, experienced major epidemics of arboviral diseases transmitted by the Aedes aegypti mosquito in recent years. These include dengue fever in 2012, Chikungunya fever in 2014 and Zika virus infection (ZIKV) in 2016. We present the emergence of the ZIKV epidemic in Jamaica and outline the national response. METHODS: The Ministry of Health's preparedness included: heightened surveillance, clinical management guidance, vector control and management, laboratory capacity strengthening, training and staffing, risk communication and public education, social mobilization, inter-sectoral collaboration, resource mobilization and international cooperation. RESULTS: The first case of ZIKV was confirmed on January 29, 2016 with date of onset of January 17, 2016. From January 3 to July 30, 2016 (Epidemiological Week (EW) 1-30), 4648 cases of ZIKV were recorded (4576 suspected, 72 laboratory-confirmed). Leading symptoms were similar among suspected and confirmed cases: rash (71% and 88%), fever (65% and 53%) and joint pains (47% and 38%). There were 17 suspected cases of Guillain Barre syndrome; 383 were reported in pregnant women, with no reports of microcephaly to date. Zika and dengue viruses were circulating predominantly in 2016. At EW30, 1744 cases of dengue were recorded (1661 suspected and 83 confirmed). Dengue serotypes 3 and 4 were circulating with 121 reports of dengue haemorrhagic fever...(AU) CONCLUSION:The possibility exists for endemicity of ZIKV similar to dengue and chikungunya in Jamaica. A ZIKV vaccine, similar to the dengue and chikungunya vaccines, is needed to be fast-tracked into clinical trials to mitigate the effects of this disease.

Incidence of neoplasia in patients with unilateral epiphora.

BACKGROUND: Nasolacrimal duct obstruction is common and is usually a result of benign stricture formation.Although neoplasia near or around the lacrimal system may produce epiphora, the incidence of neoplasia from within the lacrimal system as a cause of nasolacrimal duct obstruction is not well documented. METHODS: A retrospective study was performed on all patients undergoing dacryocystorhinostomy with a history of epiphora. The incidence of patients with operative findings of intra-lacrimal neoplasm was sought. Histopathologically confirmed cases were included. RESULTS: The study comprised 537 patients, who underwent a total of 631 endoscopic dacryocystorhinostomy procedures between January 1998 and July 2013. Non-stenotic causes of nasolacrimal duct obstruction were encountered in 3.01 per cent of dacryocystorhinostomy procedures, and included neoplastic, inflammatory and infectious pathologies. Inverted papilloma was the most common cause, encountered in 0.79 per cent of dacryocystorhinostomy operations. CONCLUSION: These findings suggest that neoplasia is an uncommon but not a rare cause of nasolacrimal duct obstruction. Surgical teams performing high numbers of dacryocystorhinostomy procedures should be aware of such pathology and patients counselled appropriately.

Mouse models for core binding factor leukemia.

RUNX1 and CBFB are among the most frequently mutated genes in human leukemias. Genetic alterations such as chromosomal translocations, copy number variations and point mutations have been widely reported to result in the malfunction of RUNX transcription factors. Leukemias arising from such alterations in RUNX family genes are collectively termed core binding factor (CBF) leukemias. Although adult CBF leukemias generally are considered a favorable risk group as compared with other forms of acute myeloid leukemia, the 5-year survival rate remains low. An improved understanding of the molecular mechanism for CBF leukemia is imperative to uncover novel treatment options. Over the years, retroviral transduction-transplantation assays and transgenic, knockin and knockout mouse models alone or in combination with mutagenesis have been used to study the roles of RUNX alterations in leukemogenesis. Although successful in inducing leukemia, the existing assays and models possess many inherent limitations. A CBF leukemia model which induces leukemia with complete penetrance and short latency would be ideal as a platform for drug discovery. Here, we summarize the currently available mouse models which have been utilized to study CBF leukemias, discuss the advantages and limitations of individual experimental systems, and propose suggestions for improvements of mouse models.

Epidural analgesia during labour - maternal understanding and experience - informed consent.

Women obtain information on epidural analgesia from various sources. For epidural for pain relief in labour this is provided by the anaesthetist as part of the consenting process. There is much discussion about the inadequacy of this consenting process; we report on women's knowledge, experience and recall of this process at a regional hospital with a 24-h epidural service. Fifty-four women were interviewed within 72 h of a vaginal birth. 91% of the women had acquired information from friends, relatives and antenatal classes. Lack of recall of benefits of epidural analgesia accounted for 26 (38%) and 25 (26%) of the responses, respectively. Similarly in terms of amount of pain relief they could expect, 13 (21%) could not remember and 13 (21%) thought that it may not work. We suggest use of varying methods of disseminating information and wider utilisation of anaesthetists in the antenatal educational programmes.