Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Relationship between gene expression patterns from nasopharyngeal swabs and serum biomarkers in patients hospitalized with COVID-19, following treatment with the neutralizing monoclonal antibody bamlanivimab.

BACKGROUND: A thorough understanding of a patient's inflammatory response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial to discerning the associated, underlying immunological processes and to the selection and implementation of treatment strategies. Defining peripheral blood biomarkers relevant to SARS-CoV-2 infection is fundamental to detecting and monitoring this systemic disease. This safety-focused study aims to monitor and characterize the immune response to SARS-CoV-2 infection via analysis of peripheral blood and nasopharyngeal swab samples obtained from patients hospitalized with Coronavirus disease 2019 (COVID-19), in the presence or absence of bamlanivimab treatment. METHODS: 23 patients hospitalized with COVID-19 were randomized to receive a single dose of the neutralizing monoclonal antibody, bamlanivimab (700 mg, 2800 mg or 7000 mg) or placebo, at study initiation (Clinical Trial; NCT04411628). Serum samples and nasopharyngeal swabs were collected at multiple time points over 1 month. A Proximity Extension Array was used to detect inflammatory profiles from protein biomarkers in the serum of hospitalized COVID-19 patients relative to age/sex-matched healthy controls. RNA sequencing was performed on nasopharyngeal swabs. A Luminex serology assay and Elecsys® Anti-SARS-CoV-2 immunoassay were used to detect endogenous antibody formation and to monitor seroconversion in each cohort over time. A mixed model for repeated measures approach was used to analyze changes in serology and serum proteins over time. RESULTS: Levels of IL-6, CXCL10, CXCL11, IFNγ and MCP-3 were > fourfold higher in the serum of patients with COVID-19 versus healthy controls and linked with observations of inflammatory and viral-induced interferon response genes detected in nasopharyngeal swab samples from the same patients. While IgA and IgM titers peaked around 7 days post-dose, IgG titers remained high, even after 28 days. Changes in biomarkers over time were not significantly different between the bamlanivimab and placebo groups. CONCLUSIONS: Similarities observed between nasopharyngeal gene expression patterns and peripheral blood biomarker profiles reveal a connection between the circulation and processes in the nasopharyngeal cavity, reinforcing the potential utility of systemic blood biomarker profiling for therapeutic monitoring of patient response. Serological antibody responses in patients correlated closely with reductions in the COVID-19 inflammatory protein biomarker signature. Bamlanivimab did not affect the biomarker dynamics in this hospitalized patient population.

Epilogue to the Gerald Maggiora Festschrift: a tribute to an exemplary mentor, colleague, collaborator, and innovator.

In May 2022, JCAMD published a Special Issue in honor of Gerald (Gerry) Maggiora, whose scientific leadership over many decades advanced the fields of computational chemistry and chemoinformatics for drug discovery. Along the way, he has impacted many researchers in both academia and the pharmaceutical industry. In this Epilogue, we explain the origins of the Festschrift and present a series of first-hand vignettes, in approximate chronological sequence, that together paint a picture of this remarkable man. Whether they highlight Gerry's endless curiosity about molecular life sciences or his willingness to challenge conventional wisdom or his generous support of junior colleagues and peers, these colleagues and collaborators are united in their appreciation of his positive influence. These tributes also reflect key trends and themes during the evolution of modern drug discovery, seen through the lens of people who worked with a visionary leader. Junior scientists will find an inspiring roadmap for creative collegiality and collaboration.

Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma.

BACKGROUND: Immune-related adverse events (irAEs) typically occur within 4 months of starting anti-programmed cell death protein 1 (PD-1)-based therapy [anti-PD-1 ± anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4)], but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAEs in patients receiving anti-PD-1-based immunotherapy. PATIENTS AND METHODS: Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD-1-based therapy and surviving >1 year. Onset, clinical features, management and outcomes of irAEs were examined. RESULTS: One hundred and eighteen patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4), with an estimated incidence of 5.3% (95% confidence interval 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53 months). Eighty-seven patients (74%) were on anti-PD-1 at irAE onset, 15 patients (12%) were <3 months from the last dose and 16 patients (14%) were >3 months from the last dose of anti-PD-1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥grade 3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD-1 and a multiple-organ irAE with onset 11 months after ceasing anti-PD-1. Early irAEs (<12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%). CONCLUSIONS: Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAEs, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD-1. The risk of delayed irAE should be considered when deciding the duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.

Theory of Planned Behavior and Perceived Role Model as Predictors of Nutrition and Physical Activity Behaviors Among College Students in Health-Related Disciplines.

Physical activity (PA) and nutrition behaviors among college students in health-related disciplines are understudied. We used theory of planned behavior (TPB) and role model beliefs (RMB) to predict PA and eating behaviors of college students in health-related programs (nurses, physical education, exercise science, and athletic training). A 26-item survey was administered among the participants. Independent variables included TPB constructs and RMB measured on a 5-point scale. PA was measured by multiplicative scores of students' number of days by the amount of time spent exercising per week. Nutrition behavior was measured using fruits (2½ c-eq/day), vegetables (2½ c-eq/day), dairy (2 c-eq/day), grains (6 oz-eq/day), and proteins (5½ oz-eq/day). Multiple regression analyses were used to predict PA and nutrition behaviors. A total of 271 college health majors (mean age 22.5 ± 4.6 years) participated in the study. The majority (56.8%) of students did not meet the weekly PA guidelines and 43.2% did not meet the recommended dietary guidelines for daily servings of food groups combined. Regression analyses showed that outcome evaluation, behavioral belief, and RMB, were significantly related with student's PA behavior and they accounted for 34%, 8%, and 1% of the variance, respectively (total R2 = 44.7). Outcome evaluation and behavioral beliefs were significantly related with nutritional behavior and they accounted for 13.3%, and 5.3% of the variance respectively (total R2 = 18.6). TPB (outcome evaluation, behavioral belief) and RMB could be used to guide programs in promoting PA and nutrition behavior among college health majors.

Young adults' human papillomavirus-related knowledge: source of medical information matters.

OBJECTIVES: Few studies examine the influence that different sources of medical information has on human papillomavirus (HPV)-related knowledge. We examined the relationship between the primary source of medical information and knowledge about HPV in young adults aged 18-26 years. STUDY DESIGN: This study used cross-sectional data from the Health Information National Trends Survey. METHODS: Respondents (n = 404) self-reported their knowledge about HPV-related diseases and vaccinations and their sources of medical information. Sources of medical information included electronic/print media, family/friends, or a healthcare provider. Bivariate and multivariate analyses were used to examine the association between the source of information and HPV knowledge. RESULTS: Fifty-six percent of respondents used electronic or print media as their primary source of medical information. A greater proportion of Hispanic (40.0%) and black (36.0%) respondents received medical information from their family/friends than white respondents (20.0%). Respondents who received medical information from family/friends had 4.34 (95% confidence interval [CI]: 2.14, 8.79), 4.06 (95% CI: 2.05, 8.04), and 2.35 (95% CI: 1.10, 5.04) times higher odds than those who received information from healthcare providers of not knowing that HPV causes cervical cancer, knowing HPV is a sexually transmitted infection, and hearing about the HPV vaccine, respectively. CONCLUSION: Source of medical information was significantly associated with knowledge of HPV. Receiving medical information from family/friends negatively influenced young adults' HPV knowledge. These findings may guide future interventions to target peer and familial influence on medical decisions.

Relationships among organ damage, social support, and depression in African American women with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) disproportionately strikes African American women. Social support can potentially reduce disease impact. The purpose of this study is to understand the relationship between organ damage and depression in African American women and how social support influences this relationship. METHODS: We used a mixed methods design, analyzing self-reported data on lupus-related organ damage, depression, and social support in 437 African American women with SLE recruited in the Georgians Organized Against Lupus (GOAL) cohort. Moreover, we conducted interviews among 15 GOAL participants to gather patients' perspectives about the role of social support in people who live with lupus. RESULTS: We found a significant association between organ damage and depression ( r = 0.163, p = 0.001), as well as between depression and social support ( F = 17.574, p < 0.001). The quantitative analysis did not render social support as a significant moderator in the organ damage-depression relationship. Interviews, however, revealed that African American women with the most severe organ damage have the greatest need for support. CONCLUSIONS: Social support is a key resource for lupus patients with high disease burden. Overall, these findings highlight the importance of monitoring depressive symptoms in this population and developing interventions aimed to increase social support available to lupus patients.

Systematic review and meta-analysis of the epidemiology of polyautoimmunity in Sjögren's syndrome (secondary Sjögren's syndrome) focusing on autoimmune rheumatic diseases.

OBJECTIVE: The epidemiology of polyautoimmunity in Sjögren's syndrome (secondary Sjögren's syndrome - sSS) is not well defined and has not been investigated before using a systematic approach. We conducted a systematic review of the epidemiology of sSS associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma, and myositis, assessing the prevalence rates (PRs) and clinical and serological features of sSS. METHOD: A systematic literature search of PubMed and Embase databases (updated to March 2016) was performed to identify all published data on PR, demographic profile, clinical manifestations, laboratory features, and causes of death associated with sSS. The PR's of sSS were summarized with PRs and 95% confidence intervals (CIs). RESULTS: The literature search identified 1639 citations, of which 42 fulfilled the inclusion criteria. Only 19 studies were of moderate to good quality and were selected for the meta-analysis. According to a random-effects model, the pooled PR for sSS associated with RA was 19.5% (95% CI 11.2 to 27.8) and the pooled PR for sSS associated with SLE was 13.96% (95% CI 8.88 to 19.04). The female/male ratio of sSS in the RA population was 14.7 (95% CI 7.09 to 256) and in the SLE population was 16.82 (95% CI 1.22 to 32.4). CONCLUSION: Prevalence rates of sSS vary widely in different populations. Both meta-analyses conducted in the RA and SLE populations were characterized by a high degree of study heterogeneity. The results of this meta-analysis highlight the need for better quality population studies.

Short-wavelength free-electron laser sources and science: a review.

This review is focused on free-electron lasers (FELs) in the hard to soft x-ray regime. The aim is to provide newcomers to the area with insights into: the basic physics of FELs, the qualities of the radiation they produce, the challenges of transmitting that radiation to end users and the diversity of current scientific applications. Initial consideration is given to FEL theory in order to provide the foundation for discussion of FEL output properties and the technical challenges of short-wavelength FELs. This is followed by an overview of existing x-ray FEL facilities, future facilities and FEL frontiers. To provide a context for information in the above sections, a detailed comparison of the photon pulse characteristics of FEL sources with those of other sources of high brightness x-rays is made. A brief summary of FEL beamline design and photon diagnostics then precedes an overview of FEL scientific applications. Recent highlights are covered in sections on structural biology, atomic and molecular physics, photochemistry, non-linear spectroscopy, shock physics, solid density plasmas. A short industrial perspective is also included to emphasise potential in this area.

Do delays in radiology lead to breaches in the 4-hour rule?

AIM: To assess trends in medical imaging requests before and after the 4-hour rule commenced and to assess the imaging time component of emergency department (ED) length of stay (LOS). MATERIALS AND METHODS: Retrospective analysis of ED patients and imaging requests 1 year prior to and 3 years after implementation of the 4-hour rule (April to December for 2011-2014) was performed at a single adult tertiary referral Level 1 trauma hospital with Level 6 ED. Logistic regression was used to evaluate trends in the number of ED patient presentations, patient triage categories, and imaging requests for these patients. The imaging component of the total ED LOS was compared for patients who met the 4-hour target and patients who did not. RESULTS: Compared to 2011 (before the 4-hour rule), ED presentations increased 4.74% in 2012, 12.7% in 2013, 21.28% in 2014 (p<0.01). Total imaging requests increased 23.05% in 2012, 48.04% in 2013, 60.77% in 2014 (p<0.01). For patients breaching the 4-hour rule, the mean time before radiology request was 2.4-2.8 hours; mean time from imaging request to completion was 1.2-1.3 hours; mean time from imaging completion to discharge from ED was the longest component of ED LOS (4.9-5.9 hours). CONCLUSIONS: There has been a significant increase in imaging requests, with a trend towards more CT and less radiography requests. Imaging requests for patients who breached the 4-hour target were made on average 2.4-2.8 hours after triage and average time after imaging in itself, exceeded 4 hours. Imaging is not likely a causative factor for patients breaching the 4-hour target.

The effect of COVID-19 on the non-COVID health outcomes of crisis-affected peoples: a systematic review.

BACKGROUND: The COVID-19 pandemic posed considerable risks to populations affected by humanitarian crises in low- and middle-income countries (LMICs). However, there is limited understanding of how the pandemic may have affected non-COVID health outcomes among crisis-affected populations. Our aim was to examine the evidence on the impact of the COVID-19 pandemic on non-COVID-19 health outcomes for crisis-affected populations in LMICs. METHODS: A systematic review methodology was applied following PRISMA guidelines. Eligibility criteria were: crisis-affected populations in LMICS; COVID-19; and all health topics, except for sexual and reproductive health which was covered in a linked review. Five bibliographic databases and additional grey literature sources were searched. The search period was from 2019 to 31 July 2022. Eligible papers were extracted and analysed using a narrative synthesis approach based on the study objectives and relevant health access and systems frameworks. A quality appraisal was also conducted. FINDINGS: 4320 articles were screened, and 15 eligible studies were identified and included in this review. Ten studies collected health outcomes data. Eight related to mental health, which generally showed worse mental health outcomes because of the pandemic, and pandemic-related stressors were identified. Two studies assessed physical health outcomes in children, while none addressed physical health outcomes among adults. Nine studies reported on access to healthcare, revealing worse access levels due to the pandemic and noting key barriers to care. Seven studies reported on the impact on health systems, with key challenges including reduced and distorted health care funding, reduced staff capacity, interrupted medicines and supplies, weak information and mixed-messaging, and weak leadership. All fifteen studies on the social determinants of health, particularly highlighting the effect of increasing poverty, the role of gender, and food insecurity on health outcomes. The quality of papers was limited overall. CONCLUSION: This review found some limited evidence indicating negative mental health effects, increased barriers to accessing care, damage to health systems and magnified impacts on the social determinants of health for crisis-affected people during the COVID-19 pandemic. However, the small number and limited quality of the studies make the overall strength of evidence quite weak.

Few-cycle pulse generation in an x-ray free-electron laser.

A method is proposed to generate trains of few-cycle x-ray pulses from a free-electron laser (FEL) amplifier via a compact "afterburner" extension consisting of several few-period undulator sections separated by electron chicane delays. Simulations show that in the hard x ray (wavelength ~0.1 nm; photon energy ~10 keV) and with peak powers approaching normal FEL saturation (GW) levels, root mean square pulse durations of 700 zs may be obtained. This is approximately two orders of magnitude shorter than that possible for normal FEL amplifier operation. The spectrum is discretely multichromatic with a bandwidth envelope increased by approximately 2 orders of magnitude over unseeded FEL amplifier operation. Such a source would significantly enhance research opportunity in atomic dynamics and push capability toward nuclear dynamics.

Transform-limited x-ray pulse generation from a high-brightness self-amplified spontaneous-emission free-electron laser.

A method to achieve high-brightness self-amplified spontaneous emission (HB-SASE) in the free-electron laser (FEL) is described. The method uses repeated nonequal electron beam delays to delocalize the collective FEL interaction and break the radiation coherence length dependence on the FEL cooperation length. The method requires no external seeding or photon optics and so is applicable at any wavelength or repetition rate. It is demonstrated, using linear theory and numerical simulations, that the radiation coherence length can be increased by approximately 2 orders of magnitude over SASE with a corresponding increase in spectral brightness. Examples are shown of HB-SASE generating transform-limited FEL pulses in the soft x-ray and near transform-limited pulses in the hard x-ray. Such pulses may greatly benefit existing applications and may also open up new areas of scientific research.

Outbreak of 2009 pandemic influenza A (H1N1) at a New York City school.

BACKGROUND: In April 2009, an outbreak of novel swine-origin influenza A (2009 H1N1 influenza) occurred at a high school in Queens, New York. We describe the outbreak and characterize the clinical and epidemiologic aspects of this novel virus. METHODS: The New York City Department of Health and Mental Hygiene characterized the outbreak through laboratory confirmation of the presence of the 2009 H1N1 virus in nasopharyngeal and oropharyngeal specimens and through information obtained from an online survey. Detailed information on exposure and the onset of symptoms was used to estimate the incubation period, generation time, and within-school reproductive number associated with 2009 H1N1 influenza, with the use of established techniques. RESULTS: From April 24 through May 8, infection with the 2009 H1N1 virus was confirmed in 124 high-school students and employees. In responses to the online questionnaire, more than 800 students and employees (35% of student respondents and 10% of employee respondents) reported having an influenza-like illness during this period. No persons with confirmed 2009 H1N1 influenza or with influenza-like illness had severe symptoms. A linkage with travel to Mexico was identified. The estimated median incubation period for confirmed 2009 H1N1 influenza was 1.4 days (95% confidence interval [CI], 1.0 to 1.8), with symptoms developing in 95% of cases by 2.2 days (95% CI, 1.7 to 2.6). The estimated median generation time was 2.7 days (95% CI, 2.0 to 3.5). We estimate that the within-school reproductive number was 3.3. CONCLUSIONS: The findings from this investigation suggest that 2009 H1N1 influenza in the high school was widespread but did not cause severe illness. The reasons for the rapid and extensive spread of influenza-like illnesses are unknown. The natural history and transmission of the 2009 H1N1 influenza virus appear to be similar to those of previously observed circulating pandemic and interpandemic influenza viruses.

Crystal response measurement of the x-ray transmission crystals used by the Imaging Spectroscopy Snout at the National Ignition Facility.

The Imaging Spectroscopy Snout (ISS) used at the National Ignition Facility is able to simultaneously collect neutron pinhole images, 1D spatially resolved x-ray spectra, and time resolved x-ray pinhole images. To measure the x-ray spectra, the ISS can be equipped with up to four different transmission crystals, each offering different energy ranges from ∼7.5 to ∼12 keV and different resolutions. Characterizing and calibrating such instruments is of paramount importance in order to extract meaningful results from experiments. More specifically, we characterized different ISS transmission-type alpha-Quartz crystals by measuring their responses as a function of photon energy, from which we inferred the angle-integrated reflectivity for each crystal's working reflections. These measurements were made at the Lawrence Livermore National Laboratory calibration station dedicated to the characterization of x-ray spectrometers. The sources used covered a wide x-ray range-from a few to 30 keV; the source diameter was ∼0.6 mm. The experimental results are discussed alongside theoretical calculations using the pyTTE model.

Treatment with a VEGFR-2 antibody results in intra-tumor immune modulation and enhances anti-tumor efficacy of PD-L1 blockade in syngeneic murine tumor models.

Prolonged activation of vascular endothelial growth factor receptor-2 (VEGFR-2) due to mis-regulation of the VEGF pathway induces aberrant blood vessel expansion, which supports growth and survival of solid tumors. Therapeutic interventions that inhibit the VEGFR-2 pathway have therefore become a mainstay of cancer treatment. Non-clinical studies have recently revealed that blockade of angiogenesis can modulate the tumor microenvironment and enhance the efficacy of concurrent immune therapies. Ramucirumab is an FDA-approved anti-angiogenic antibody that inhibits VEGFR-2 and is currently being evaluated in clinical studies in combination with anti-programmed cell death (PD-1) axis checkpoint inhibitors (pembrolizumab, durvalumab, or sintilimab) across several cancer types. The purpose of this study is to establish a mechanistic basis for the enhanced activity observed in the combined blockade of VEGFR-2 and PD-1-axis pathways. Pre-clinical studies were conducted in murine tumor models known to be responsive to anti-PD-1 axis therapy, using monoclonal antibodies that block mouse VEGFR-2 and programmed death-ligand 1 (PD-L1). Combination therapy resulted in enhanced anti-tumor activity compared to anti-PD-L1 monotherapy. VEGFR-2 blockade at early timepoints post-anti-PD-L1 therapy resulted in a dose-dependent and transient enhanced infiltration of T cells, and establishment of immunological memory. VEGFR-2 blockade at later timepoints resulted in enhancement of anti-PD-L1-driven immune cell infiltration. VEGFR-2 and PD-L1 monotherapies induced both unique and overlapping patterns of immune gene expression, and combination therapy resulted in an enhanced immune activation signature. Collectively, these results provide new and actionable insights into the mechanisms by which concurrent VEGFR-2 and PD-L1 antibody therapy leads to enhanced anti-tumor efficacy.

Occult tension pneumothorax discovered following imaging for adult trauma patients in the modern major trauma system: a multicentre observational study.

BACKGROUND: Tension pneumothorax following trauma is a life-threatening emergency and radiological investigation is normally discouraged prior to treatment in traditional trauma doctrines such as ATLS. Some trauma patients may be physiologically stable enough for diagnostic imaging and occult tension pneumothorax is discovered radiologically. We assessed the outcomes of these patients and compared them with those with clinical diagnosis of tension pneumothorax prior to imaging. METHODS: A multicentre civilian-military collaborative network of six major trauma centres in the UK collected observational data from adult patients who had a diagnosis of traumatic tension pneumothorax during a 33-month period. Patients were divided into 'radiological' (diagnosis following CT/CXR) or 'clinical' (no prior CT/CXR) groups. The effect of radiological diagnosis on survival was analysed using multivariable logistic regression that included the covariates of age, gender, comorbidities and Injury Severity Score. RESULTS: There were 133 patients, with a median age of 41 (IQR 24-61); 108 (81%) were male. Survivors included 49 of 59 (83%) in the radiological group and 59 of 74 (80%) in the clinical group (p=0.487). Multivariable logistic regression showed no significant association between radiological diagnosis and survival (OR 2.40, 95% CI 0.80 to 7.95; p=0.130). There was no significant difference in mortality between the groups. CONCLUSION: Radiological imaging may be appropriate for selected trauma patients at risk of tension pneumothorax if they are considered haemodynamically stable. Trauma patients may be physiologically stable enough for radiological imaging but have occult tension pneumothorax because they did not have the typical clinical presentation. The historical dogma of the 'forbidden scan' no longer applies to such patients.

A 2-4 keV multilayer mirrored channel for the NIF Dante system.

During inertial confinement fusion experiments at the National Ignition Facility (NIF), a capsule filled with deuterium and tritium (DT) gas, surrounded by a DT ice layer and a high-density carbon ablator, is driven to the temperature and densities required to initiate fusion. In the indirect method, 2 MJ of NIF laser light heats the inside of a gold hohlraum to a radiation temperature of 300 eV; thermal x rays from the hohlraum interior couple to the capsule and create a central hotspot at tens of millions degrees Kelvin and a density of 100-200 g/cm3. During the laser interaction with the gold wall, m-band x rays are produced at ∼2.5 keV; these can penetrate into the capsule and preheat the ablator and DT fuel. Preheat can impact instability growth rates in the ablation front and at the fuel-ablator interface. Monitoring the hohlraum x-ray spectrum throughout the implosion is, therefore, critical; for this purpose, a Multilayer Mirror (MLM) with flat response in the 2-4 keV range has been installed in the NIF 37° Dante calorimeter. Precision engineering and x-ray calibration of components mean the channel will report 2-4 keV spectral power with an uncertainty of ±8.7%.

Functional Outcome of Kyphoplasty in Osteoporotic Vertebral Fractures in Patients with Severe Disability Above 60 Years of Age: Mid to Long Term Follow up.

BACKGROUND:  Vertebral osteoporotic fractures are a worldwide problem and can cause significant morbidity. MATERIAL AND METHODS: retrospective analysis reviewing functional outcome of 70 patients who underwent balloon-kyphoplasty(BK). Inclusion criteria, a-patients above 60 years of age b-symptomatic patients who failed conservative treatment c-radiological diagnosis of vertebral compression fracture(VCF). Primary outcome was evaluation of functional outcome in mid- (1-3 years) and long term (>3 years). Secondary outcomes a-analysis of the functional outcome of patients with severe disability or worse in mid- and long-term b-comparison of functional outcome between mid-term and long term follow-up c-correlate number of levels operated on with functional outcome. RESULTS: There were 70 patients with average age of 74 years. Lumbar and thoracic VCFs were included. Average follow-up was 2.7 years. Twenty-eight patients had long-term follow-up of ≥ 3 years and the remaining 42 had mid-term follow-up of > 1 year and < 3 years. All patients experienced clinical and statistically significant improvement in their Oswestry Disability Index score. This was the case in mid-term and long-term follow-up. This was also the case for patients presenting with severe disability. There was no correlation between the number of levels and functional outcome. CONCLUSIONS: 1. Osteoporotic vertebral compression fractures are fragility fractures and can be associated with significant morbidity. 2. Surgical treatment can help improve functional outcome on failure of conservative treatment. 3. Balloon kyphoplasty can significantly improve pa-tients' functional outcome in mid-term and long-term follow-up including patients presenting with severe disability or worse. 4. This study is of value in consenting kyphoplasty patients as they can expect an improvement in their disability in the mid-to-long term.