Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Prehospital Active and Passive Warming in Trauma Patients.

OBJECTIVE: Hypothermia is common among trauma patients and can lead to a serious rise in morbidity and mortality. This study was performed to investigate the effect of active and passive warming measures implemented in the prehospital phase on the body temperature of trauma patients. METHODS: In a multicenter, multinational prospective observational design, the effect of active and passive warming measures on the incidence of hypothermia was investigated. Adult trauma patients who were transported by helicopter emergency medical services (HEMS) or ground emergency medical services with an HEMS physician directly from the scene of injury were included. Four HEMS/ground emergency medical services programs from Canada, the United States, and the Netherlands participated. RESULTS: A total of 80 patients (n = 20 per site) were included. Eleven percent had hypothermia on presentation, and the initial evaluation occurred predominantly within 60 minutes after injury. In-line fluid warmers and blankets were the most frequently used active and passive warming measures, respectively. Independent risk factors for a negative change in body temperature were transportation by ground ambulance (odds ratio = 3.20; 95% confidence interval, 1.06-11.49; P = .03) and being wet on initial presentation (odds ratio = 3.64; 95% confidence interval, 0.99-13.36; P = .05). CONCLUSION: For adult patients transported from the scene of injury to a trauma center, active and passive warming measures, most notably the removal of wet clothing, were associated with a favorable outcome, whereas wet patients and ground ambulance transport were associated with an unfavorable outcome with respect to temperature.

Degassing of early-formed planetesimals restricted water delivery to Earth.

The timing of delivery and the types of body that contributed volatiles to the terrestrial planets remain highly debated1,2. For example, it is unknown if differentiated bodies, such as that responsible for the Moon-forming giant impact, could have delivered substantial volatiles3,4 or if smaller, undifferentiated objects were more probable vehicles of water delivery5-7. Here we show that the water contents of minerals in achondrite meteorites (mantles or crusts of differentiated planetesimals) from both the inner and outer portions of the early Solar System are ≤2 µg g-1 H2O. These are among the lowest values ever reported for extraterrestrial minerals. Our results demonstrate that differentiated planetesimals efficiently degassed before or during melting. This finding implies that substantial amounts of water could only have been delivered to Earth by means of unmelted material.

Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer and diabetes. METHODS: This was a retrospective propensity score-matched cohort study involving adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalisation for incident HF and all-cause mortality. The secondary outcomes were serious adverse events associated with SGLT2i. RESULTS: From a total of 8640 patients, 878 SGLT2i recipients were matched to non-recipients. During a median follow-up of 18.8 months, SGLT2i recipients had a threefold lower rate of hospitalisation for incident HF compared with non-SGLT2i recipients (2.92 vs 8.95 per 1000 patient-years, p=0.018). In Cox regression and competing regression models, SGLT2i were associated with a 72% reduction in the risk of hospitalisation for HF (HR 0.28 (95% CI: 0.11 to 0.77), p=0.013; subdistribution HR 0.32 (95% CI: 0.12 to 0.84), p=0.021). The use of SGLT2i was also associated with a higher overall survival (85.3% vs 63.0% at 2 years, p<0.001). The risk of serious adverse events such as hypoglycaemia and sepsis was similar between the two groups. CONCLUSIONS: The use of SGLT2i was associated with a lower rate of incident HF and prolonged overall survival in patients with cancer with diabetes mellitus.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.

OBJECTIVE: To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. DESIGN: Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. RESULTS: No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. CONCLUSIONS: Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.

A mesoscale finite element modeling approach for understanding brain morphology and material heterogeneity effects in chronic traumatic encephalopathy.

Chronic Traumatic Encephalopathy (CTE) affects a significant portion of athletes in contact sports but is difficult to quantify using clinical examinations and modeling approaches. We use an in silico approach to quantify CTE biomechanics using mesoscale Finite Element (FE) analysis that bridges with macroscale whole head FE analysis. The sulci geometry produces complex stress waves that interact with one another to create increased shear stresses at the sulci depth that are significantly larger than in analyses without sulci (from 0.5 to 18.0 kPa). Sulci peak stress concentration regions coincide with experimentally observed CTE sites documented in the literature. HighlightsSulci introduce stress localizations at their depth in the gray matterSulci stress fields interact to produce stress concentration sites in white matterDifferentiating brain tissue properties did not significantly affect peak stresses.

Certolizumab pegol for the treatment of patients with moderate-to-severe chronic plaque psoriasis: pooled analysis of week 16 data from three randomized controlled trials.

BACKGROUND: Certolizumab pegol, an Fc-free, PEGylated, anti-tumour necrosis factor (TNF) biologic, has demonstrated favourable results in three ongoing, phase 3, randomized, double-blinded, placebo-controlled trials in adults with psoriasis. OBJECTIVE: Data were pooled from the ongoing trials to investigate efficacy in selected subgroups and add precision to estimates of treatment effects during the initial 16 weeks of treatment. METHODS: In each trial, patients ≥18 years with moderate-to-severe chronic plaque psoriasis for ≥6 months were randomized to receive certolizumab 400 mg, certolizumab 200 mg or placebo every 2 weeks for 16 weeks. Coprimary endpoints for the pooled analysis were responder rates at Week 16, defined as ≥75% reduction in psoriasis area and severity index (PASI 75) and physician global assessment (PGA) of 0/1 ('clear'/'almost clear' with ≥2-category improvement). Safety was assessed by treatment-emergent adverse events. RESULTS: A total of 850 patients treated with certolizumab 400 mg (N = 342), certolizumab 200 mg (N = 351) or placebo (N = 157) were included in the pooled analysis. At Week 16, PASI 75 and PGA 0/1 responder rates were 80.1% and 63.7% in the certolizumab 400 mg group, 74.5% and 54.6% in the certolizumab 200 mg group, and 7.5% and 2.8% in the placebo group (P < 0.0001 for each dose versus placebo). In patients with and without prior biologic therapy, both doses of certolizumab resulted in substantially higher responder rates versus placebo. The incidence of adverse events was generally similar between the 400 mg and placebo groups, and somewhat lower in the 200 mg group versus placebo. No new safety signals were identified. CONCLUSION: Certolizumab pegol 400 mg or 200 mg every 2 weeks for 16 weeks was associated with statistically significant and clinically meaningful improvements in signs and symptoms of psoriasis in patients with and without prior biologic therapy, and a safety profile consistent with the anti-TNF class in psoriasis.

Development and characterisation of polymeric microparticle of poly(d,l-lactic acid) loaded with holmium acetylacetonate.

Biodegradable polymers containing radioactive isotopes such as Holmium 166 (166Ho) have potential applications as beta particle emitters in tumour tissues. It is also a gamma ray emitter, allowing nuclear imaging of any tissue to be acquired. It is frequently used in the form of complexes such as holmium acetylacetonate (HoAcAc), which may cause damages in tissues next to the targets cancer cells, as it is difficult to control its linkage or healthy tissues radiotherapy effects. Poly(d,l-lactic acid), PDLLA, was used to encapsulate holmium acetylacetonate (HoAcAc) using an emulsion solvent extraction/evaporation technique. Microspheres with sizes between 20-53 µm were extensively characterised. HoAcAc release from the microspheres was assessed through studies using Inductively Coupled Plasma - Optical Emission Spectroscopy, and the microspheres showed no holmium leakage after a period of 10 half-lives and following gamma irradiation. Thus, HoAcAc loaded microspheres are here presented as a potential system for brachytherapy and imaging purposes.

Manifestations and mechanisms of myocardial lipotoxicity in obesity.

Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is amongst the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodelling and diastolic dysfunction. Obesity-associated perturbations in myocardial and systemic lipid metabolism are important contributors to cardiovascular complications of obesity. Accumulation of excess lipid in nonadipose cells of the cardiovascular system can cause cell dysfunction and cell death, a process known as lipotoxicity. Lipotoxicity has been modelled in mice using high-fat diet feeding, inbred lines with mutations in leptin receptor signalling, and in genetically engineered mice with enhanced myocardial fatty acid uptake, altered lipid droplet homoeostasis or decreased cardiac fatty acid oxidation. These studies, along with findings in cell culture model systems, indicate that the molecular pathophysiology of lipid overload involves endoplasmic reticulum stress, alterations in autophagy, de novo ceramide synthesis, oxidative stress, inflammation and changes in gene expression. We highlight recent advances that extend our understanding of the impact of obesity and altered lipid metabolism on cardiac function.

Do Tanzanian hospitals need healthcare ethics committees? report on the 2014 dartmouth/penn research ethics training and program development for tanzania (DPRET) workshop

Ethical issues are common in the global community. The shortage of human and medical resources when working with vulnerable populations requires institutional support to address the challenges that often arise in the patient-provider relationship. The 2014 Dartmouth/Penn Research Ethics Training and Program Development for Tanzania (DPRET) workshop centred on discussions about research and clinical ethics issues unique to Tanzanian healthcare providers. This article discusses some of the ethical challenges that workshop participants reported in their day-to-day work life with patients and families, such as truth-telling, disagreements over treatment plans and patient distrust of local physicians and hospital staff, among others. The Tanzanian participants recognised the need for supportive mechanisms within their local hospital environments. Further dialogue and research on the development ofinstitutional ethics committees within hospital systems is critically needed so that healthcare providers can meet their ethical and professional obligations to patients and families and address ethical conflicts that arise in a timely and productive fashion

Disparities in Obesity, Physical Activity Rates, and Breast Cancer Survival.

The significantly higher breast cancer (BCa) mortality rates of African-American (AA) women compared to non-Hispanic (NHW) white women constitute a major US health disparity. Investigations have primarily focused on biological differences in tumors to explain more aggressive forms of BCa in AA women. The biology of tumors cannot be modified, yet lifestyle changes can mitigate their progression and recurrence. AA communities have higher percentages of obesity than NHWs and exhibit inefficient access to care, low socioeconomic status, and reduced education levels. Such factors are associated with limited healthy food options and sedentary activity. AA women have the highest prevalence of obesity than any other racial/ethnic/gender group in the United States. The social ecological model (SEM) is a conceptual framework on which interventions could be developed to reduce obesity. The SEM includes intrapersonal factors, interpersonal factors, organizational relationships, and community/institutional policies that are more effective in behavior modification than isolation from the participants' environmental context. Implementation of SEM-based interventions in AA communities could positively modify lifestyle behaviors, which could also serve as a powerful tool in reducing risk of BCa, BCa progression, and BCa recurrence in populations of AA women.

The Perception of Art among Patients and Staff on a Renal Dialysis Unit.

This study investigated the purpose and effectiveness of giving outpatients an opportunity to engage in art activities while receiving dialysis treatment. A mixed method study was conducted. 21 semi-structured interviews were conducted with outpatients attending the dialysis unit and 13 surveys of clinicians were completed. The principle reasons to partake in the art activity programme included: to pass time, to relieve boredom, to be creative, to try something new, distraction from concerns, to stay positive and to achieve something new. Patients who did not participate in the programme pass their time primarily by watching TV or sleeping. All staff who partook in the survey were satisfied with the programme and wanted it to continue. Our findings indicate that the creative arts programme is viewed positively by staff and patients alike, and might be useful in other hospital departments. Further in depth qualitative research would be useful to interrogate the potential effect of engagement in art on positive mental health and quality of life for patients with chronic conditions.

CDKN2A-independent role of BMI1 in promoting growth and survival of Ph+ acute lymphoblastic leukemia.

BMI1 is a key component of the PRC1 (polycomb repressive complex-1) complex required for maintenance of normal and cancer stem cells. Its aberrant expression is detected in chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia (ALL), but no data exist on BMI1 requirement in ALL cells. We show here that BMI1 expression is important for proliferation and survival of Ph+ ALL cells and for leukemogenesis of Ph+ cells in vivo. Levels of BIM, interferon-α (IFNα)-regulated genes and E2F7 were upregulated in BMI1-silenced cells, suggesting that repressing their expression is important for BMI1 biological effects. Consistent with this hypothesis, we found that: (i) downregulation of BIM or E2F7 abrogated apoptosis or rescued, in part, the reduced proliferation and colony formation of BMI1 silenced BV173 cells; (ii) BIM/E2F7 double silencing further enhanced colony formation and in vivo leukemogenesis of BMI1-silenced cells; (iii) overexpression of BIM and E2F7 mimicked the effect of BMI1 silencing in BV173 and SUP-B15 cells; and (iv) treatment with IFNα suppressed proliferation and colony formation of Ph+ ALL cells. These studies indicate that the growth-promoting effects of BMI1 in Ph+ ALL cells depend on suppression of multiple pathways and support the use of IFNα in the therapy of Ph+ ALL.

Effect of certolizumab pegol over 96†weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure.

OBJECTIVE: Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. METHODS: RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. RESULTS: Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. CONCLUSIONS: CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. TRIAL REGISTRATION NUMBER: NCT01087788.

Treatment of renal artery aneurysms.

Renal artery aneurysms (RAAs) represent a rare disease and are most commonly discovered as an incidental imaging finding. RAA may be associated with hypertension and are usually asymptomatic at presentation but may result in rupture, hematuria, or renal infarction. The natural history of RAA is poorly understood. Although there is general consensus that RAA that are symptomatic or identified in women at risk for pregnancy should be repaired, diameter criteria for repair of asymptomatic RAA are controversial and emerging evidence suggests that rupture incidence is low for those <2.5 cm in diameter. Options for repair of RAA have expanded over the preceding decades with expansion of both open surgical and endovascular treatments.

Applicability of the EORTC/MSG criteria for IFD in clinical practice.

Invasive fungal disease (IFD) is a feared complication in patients with hematological malignancies. In 2008, the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG) published updated criteria for the diagnostic workup within clinical studies for immunosuppressed patients with suspected fungal infection. We applied these criteria in a routine clinical setting with regard to their feasibility for bedside practice at our institution in a 1-year period. One hundred seventy consecutive patients with a recent history of chemotherapy-induced neutropenia (n = 100) or allogeneic stem cell recipients (n = 70) who had received a CT scan of the chest in search of pulmonary IFD were examined. We analyzed all available radiological and microbiological data according to the EORTC/MSG criteria. The quality of images was good in 94.7%, microbiological diagnostics performed in 94.1% patients. Five patients had histopathologic-proven IFD, 18 patients were classified as "probable," 55 patients as "possible" IFD, and 92 patients did not fulfill any criteria ("no IFD"). Microbiology revealed suggestive findings in 29 patients. These were either galactomannan antigen (Gm-AG) in serum (n = 18) and/or broncho-alveolar lavage (BAL) (n = 5). CT scan showed pulmonary infiltrates in 106 patients; 78 were classified as typical for IPA, further discriminated by morphology and number of nodules, as well as additional signs (halo, air crescent, cavity). We observed a better overall survival in patients without infiltrates compared to those with any type of infiltrate (p = 0.042) and a trend toward favorable survival in patients who had micronodular lesions (p = 0.058). We also found a higher probability of Gm-AG positivity in the group of allogeneic stem cell transplantation (allo-SCT) patients (p = 0.001) and a trend toward an association of Gm-AG positivity and positive findings on CT (p = 0.054). The applicability of criteria was good, both with regard to radiological and mycological evidence and sufficient for the categorization of IFD according to EORTC/MSG in the clinical setting. However, our findings suggest that feasibility improves with stringency of mycological workup, which is reflected in the two subgroups. Radiology harvests by far more suggestive findings which can only partly be correlated with mycological evidence. Although feasible, whether the EORTC/MSG criteria are the appropriate tool for early identification of IFD remains open for discussion.

Proxy measures of vitamin D status - season and latitude - correlate with adverse outcomes after bariatric surgery in the Nationwide Inpatient Sample, 2001-2010: a retrospective cohort study.

OBJECTIVE: To investigate the association between adverse surgical outcomes following bariatric surgery and proxy measures of vitamin D (VitD) status (season and latitude) in the Nationwide Inpatient Sample (NIS). BACKGROUND: Obesity is an independent risk factor for VitD deficiency (25(OH)D < 20 ng ml-1). VitD deficiency compounds the chronic inflammation of obesity, increasing the risk of adverse outcomes following bariatric surgery. Epidemiology has long used season and latitude as proxies for group VitD, as VitD status is largely determined by sun exposure, which is greatest during summer and at the Equator. METHODS: We assessed proxy measures of group VitD status. We compared surgeries in VitD Summer (July to September), Winter (January to March), and Fall/Spring (October to December and April to June) and in the North (≥37°N) vs. the South (<37°N). RESULTS: We identified 932,091 bariatric surgeries; 81.2% were women and 74.4% were white. Sex was unequally distributed by season (p = 0.005). Median age was 43.0 years (all groups). Most surgeries occurred in the North (64.8%). Adverse outcome rates ranged from 0.01% (wound infections) to 39.4% [prolonged length of stay {LOS}]. Season was inversely associated with wound infection (p = 0.018) and dehiscence (p = 0.001). Extended LOS was inversely correlated with season (p < 0.001). These relationships held after adjustment. Prolonged LOS (p < 0.001) and any complication (p = 0.108) were more common in the North. CONCLUSIONS: We have demonstrated a graded relationship between seasonality and adverse outcomes following bariatric surgery. The association was strongest for dehiscence and prolonged LOS. These relationships held when using latitude. A prospective study measuring pre-operative 25(OH)D concentration would strengthen the case for causality in adverse surgical outcomes.

Effects of meal composition on postprandial incretin, glucose and insulin responses after surgical and medical weight loss.

BACKGROUND: Meal tolerance tests are frequently used to study dynamic incretin and insulin responses in the postprandial state; however, the optimal meal that is best tolerated and suited for hormonal response following surgical and medical weight loss has yet to be determined. OBJECTIVE: To evaluate the tolerability and effectiveness of different test meals in inducing detectable changes in markers of glucose metabolism in individuals who have undergone a weight loss intervention. METHODS: Six individuals who underwent surgical or medical weight loss (two Roux-en-Y gastric bypass, two sleeve gastrectomy and two medical weight loss) each completed three meal tolerance tests using liquid-mixed, solid-mixed and high-fat test meals. The tolerability of each test meal, as determined by the total amount consumed and palatability, as well as fasting and meal-stimulated glucagon-like peptide, glucose-dependent insulinotropic polypeptide, insulin and glucose were measured. RESULTS: Among the six individuals, the liquid-mixed meal was better and more uniformly tolerated with a median meal completion rate of 99%. Among the four bariatric surgical patients, liquid-mixed meal stimulated on average a higher glucagon-like peptide (percent difference: 83.7, 89), insulin secretion (percent difference: 155.1, 158.7) and glucose-dependent insulinotropic polypeptide (percent difference: 113.5, 34.3) compared with solid-mixed and high-fat meals. CONCLUSIONS: The liquid-mixed meal was better tolerated with higher incretin and insulin response compared with the high-fat and solid-mixed meals and is best suited for the evaluation of stimulated glucose homeostasis.

First measurements of hydrodynamic instability growth in indirectly driven implosions at ignition-relevant conditions on the National Ignition Facility.

Ignition experiments have shown an anomalous susceptibility to hydrodynamic instability growth. To help understand these results, the first hydrodynamic instability growth measurements in indirectly driven implosions on the National Ignition Facility were performed at ignition conditions with peak radiation temperatures up to ∼300 eV. Plastic capsules with two-dimensional preimposed, sinusoidal outer surface modulations of initial wavelengths of 240 (corresponding to a Legendre mode number of 30), 120 (mode 60), and 80 µm (mode 90) were imploded by using actual low-adiabat ignition laser pulses. The measured growth was in excellent agreement, validating 2D hydra simulations for the most dangerous modes in the acceleration phase. These results reinforce confidence in the predictive capability of calculations that are paramount to illuminating the path toward ignition.