A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

SOX9+ enthesis cells are associated with spinal ankylosis in ankylosing spondylitis.

OBJECTIVE: Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known. DESIGN: To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques. Enthesis cells were isolated, characterized, stimulated with TNF and/or IL-17A, and analysed by cell-based experimental tools. RESULTS: We found diffusely distributed granular tissue and cartilage in the subchondral bone in AS. Co-expression of SOX9, a specific transcription factor in cartilage, and matrix metalloproteinase 13 (MMP13) was found in the granular tissues within the subchondral bone from AS patients. Intriguingly, SOX9 expression was significantly higher in AS enthesis cells than controls and correlated with TNFR1 and IL-17RA expressions, which is important for high reactivity to TNF and IL-17A cytokines. Co-stimulation by TNF and IL-17A resulted in accelerated mineralization/calcification features, and increased OCN expression in AS enthesis cells. Furthermore, SOX9 overexpression in enthesis leads to promoting mineralization feature by TNF and IL-17A stimuli. Finally, OCN expression is elevated in the destructive enthesis of advanced AS. CONCLUSION: These findings provide insight into the links between inflammation and the mineralization of entheseal tissue as the initiation of spinal ankylosis, emphasizing the importance of SOX9+ enthesis cells.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Fracture recurrence in hip fracture with menopausal hormone therapy versus risedronate: a clinical trial.

OBJECTIVES: An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture. METHODS: Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD). RESULTS: Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group. CONCLUSIONS: MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.

Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial.

BACKGROUND: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. PATIENTS AND METHODS: In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. RESULTS: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was -12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). CONCLUSION: XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (number NCT01470443).

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): a phase III, international, randomized, placebo-controlled study.

Background: Angiogenesis is critical to colorectal cancer (CRC) growth and metastasis. Phase I/II studies have demonstrated the efficacy of nintedanib, a triple angiokinase inhibitor, in patients with metastatic CRC. This global, randomized, phase III study investigated the efficacy and safety of nintedanib in patients with refractory CRC after failure of standard therapies. Patients and methods: Eligible patients (Eastern Cooperative Oncology Group performance status 0-1, with histologically/cytologically confirmed metastatic/locally advanced CRC adenocarcinoma unamenable to surgery and/or radiotherapy) were randomized 1 : 1 to receive nintedanib (200 mg twice daily) or placebo (twice daily), until disease progression or undue toxicity. Patients were stratified by previous regorafenib, time from onset of metastatic disease to randomization, and region. Co-primary end points were overall survival (OS) and progression-free survival (PFS) by central review. Secondary end points included objective tumor response and disease control by central review. Results: From October 2014 to January 2016, 768 patients were randomized; 765 were treated (nintedanib n = 384; placebo n = 381). Median follow-up was 13.4 months (interquartile range 11.1-15.7). OS was not improved [median OS 6.4 months with nintedanib versus 6.0 months with placebo; hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.86-1.19; P = 0.8659]. There was a significant but modest increase in PFS with nintedanib versus placebo (median PFS 1.5 versus 1.4 months, respectively; HR 0.58; 95% CI 0.49-0.69; P < 0.0001). There were no complete or partial responses. Adverse events (AEs) occurred in 97% of 384 nintedanib-treated patients and 93% of 381 placebo-treated patients. The most frequent grade ≥3 AEs were liver-related AEs (nintedanib 16%; placebo 8%) and fatigue (nintedanib 9%; placebo 6%). Conclusions: The study failed to meet both co-primary end points. Nintedanib did not improve OS and was associated with a significant but modest increase in PFS versus placebo. Nintedanib was well tolerated. ClinicalTrials.gov number: NCT02149108 (LUME-Colon 1).

Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients.

Background: To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics. Patients and methods: We prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples. Results: Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications. Conclusions: The present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.

Incidence, risk factors, and fracture healing of atypical femoral fractures: a multicenter case-control study.

The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment. INTRODUCTION: To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing. METHODS: We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing. RESULTS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1-17 years). The use of BPs was significantly associated with AFFs (p < 0.001, odds ratio = 25.65; 95% confidence interval = 10.74-61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment. CONCLUSIONS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.

Measurement of Reactor Antineutrino Oscillation Amplitude and Frequency at RENO.

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

Globular adiponectin acts as a melanogenic signal in human epidermal melanocytes.

BACKGROUND: Adiponectin is an adipocyte-derived cytokine that circulates as a full-length protein and a fragment containing the globular domain of adiponectin (gAd). A recent study has reported the antimelanogenic effects of full-length adiponectin. OBJECTIVES: To examine the involvement of gAd in melanogenesis and its mechanisms of action. METHODS: The effects of gAd on melanogenesis and its mechanisms of action were investigated in human epidermal melanocytes and reconstructed epidermis, including melanin content, cellular tyrosinase activity, cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activity, expression and phosphorylation of signalling molecules. RESULTS: Exogenous gAd increased melanin content, and the mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes TRP1, but not TRP2, were increased by gAd. However, cAMP production and PKA activity were not affected by gAd. Moreover, attempts to elucidate the underlying mechanism behind the gAd-mediated effect revealed that gAd could regulate melanogenesis by upregulating MITF through phosphorylation of the cAMP response element-binding protein (CREB). In addition, upregulation of MITF was mediated by activation of adenosine monophosphate-activated protein kinase (AMPK)-p38 mitogen-activated protein kinase (MAPK) signalling. Taken together, these findings indicate that promotion of melanogenesis by gAd occurs through increased expression of MITF, which is mediated by activation of the AMPK-p38 MAPK-CREB pathway. CONCLUSIONS: These findings suggest that gAd contributes to epidermal homeostasis via its effect on melanocyte biology, and products of adipose tissue could affect epidermal biology.

Oestradiol-17ß is a local factor inducing the early stage of spermatogenesis in mouse testes.

This study was undertaken to elucidate the effect of testicular oestradiol-17ß (E2 ) on spermatogenesis. Spermatogonial development and spermatogenic gene expression in testicular germ cells were investigated using an in vitro culture system supplemented with E2 . E2 stimulated spermatocytogenic development of cultured testicular germ cells regardless of the addition of follicle-stimulating hormone and testosterone to the culture medium. E2 also induced the expression of genes encoding synaptonemal complex protein 1 and protamine 1, proteins required for spermatogenesis. In conclusion, the results of this study suggest that E2 is a spermatocytogenic factor that acts via the stimulation of spermatogenic gene expression.

Paternal age as an independent factor does not affect embryo quality and pregnancy outcomes of testicular sperm extraction-intracytoplasmic sperm injection in azoospermia.

This study was performed to evaluate the independent influence of paternal age affecting embryo development and pregnancy using testicular sperm extraction (TESE)-intracytoplasmic sperm injection (ICSI) in obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). Paternal patients were divided into the following groups: ≤30 years, 31-35 years, 36-40 years, 41-45 years and ≥46 years. There were no differences in the rates of fertilisation or embryo quality according to paternal and maternal age. However, clinical pregnancy and implantation rates were significantly lower between those ≥46 years of paternal age compared with other age groups. Fertilisation rate was higher in the OA than the NOA, while embryo quality, pregnancy and delivery results were similar. Clinical pregnancy and implantation rates were significantly lower for patients ≥46 years of paternal age compared with younger age groups. In conclusion, fertilisation using TESE in azoospermia was not affected by the independent influence of paternal age; however, as maternal age increased concomitantly with paternal age, rates of pregnancy and delivery differed between those with paternal age <41 years and ≥46 years. Therefore, paternal age ≥46 years old should be considered when applying TESE-ICSI in cases of azoospermia, and patients should be advised of the associated low pregnancy rates.

Comparison of weighted and composite scores for pre-clinical dental learners.

PURPOSE: The weighted mean (WM) method for combining scores of assessment components can provide outcomes with biased reliability and score precision. The objective of this study was to compare the traditional WM with another method utilising the composite score (CS) principle for combining scores of a final summative assessment exercise for a pre-clinical dental course. METHODS: Data were collected from the final examination of third-year Preclinical Operative and Esthetic Dentistry course consisting of 3 parts: practical competency, objective structured practical examination and a written examination with weights of 33%, 17% and 50%, respectively. Scores from the 3 components were combined using the WM and CS methods. Weighted kappa was used to compare both approaches for agreement, and students' ranks were also compared. RESULTS: Combining scores using CS scheme produced lower scores overall compared to WM with more apparent effect for the male group. Agreement between WM and CS was moderate (κ = 0.44) with major differences between students' ranks across the 2 modalities as only 21% of the cohort retained their ranks. CONCLUSION: The CS method produced more reliable scores, resulting in moderate agreement with the WM and major shift in students' ranks. These findings necessitate further validity considerations before implementing the CS method and call for further studies that examine the consequences of composite measures in dental education.

Rapamycin-insensitive companion of mTOR (RICTOR) amplification defines a subset of advanced gastric cancer and is sensitive to AZD2014-mediated mTORC1/2 inhibition.

Background: Targeting oncogenic genomic aberrations is an established therapeutic strategy in multiple tumor types. Molecular classification has uncovered a number of novel targets, and rapamycin-insensitive companion of mTOR (RICTOR) amplification has been identified in lung cancer. Further investigation assessing the therapeutic potential of RICTOR amplification as a novel target across advanced cancers is needed. Patients and methods: Tumor samples from 640 patients with metastatic solid tumors, primarily gastrointestinal and lung cancers were prospectively subjected to a next-generation sequencing (NGS) assay to identify molecular targets. Samples with NGS-detected RICTOR amplification were confirmed with FISH. A RICTOR-amplified patient-derived cell (PDC) line was generated and used to investigate the effectiveness of selective AKT, mTORC1, and mTORC1/2 inhibition. Results: NGS identified 13 (2%) of 640 patients with RICTOR-amplified tumors (6 gastric, 3 NSCLC, 1 SCLC, 1 CRC, 1 sarcoma, 1 MUO). Of the 13 patients, seven patients had RICTOR protein overexpression by IHC. The prevalence of RICTOR amplification in gastric cancer by NGS was 3.8% (6/160). FISH testing confirmed amplification (RICTOR/control >2) in 5/13 (38%) of samples, including four gastric cancers and one lung cancer. Treatment of a RICTOR amplified PDC with a selective AKT (AZD5363), selective mTORC1 (everolimus), dual mTORC1/2 (AZD2014), and the multi-target kinase inhibitor pazopanib demonstrated preferential sensitivity to the mTORC1/2 inhibitor (AZD2014). Knockdown of RICTOR reversed PDC sensitivity to AZD2014, validating the importance of RICTOR amplification to the PDC line. Conclusions: RICTOR amplification is a rare but therapeutically relevant genomic alteration across solid tumors. Our results support further pre-clinical and clinical investigation with AZD2014 in RICTOR amplified gastric cancer and highlights the importance of genomic profiling.

Vertebral bone attenuation on low-dose chest CT: quantitative volumetric analysis for bone fragility assessment.

This study evaluated the use of low-dose chest computed tomography (LDCT) for detecting bone fragility. LDCT-measured vertebral bone attenuation by volumetric methods showed good correlation with bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA, and good diagnostic performance for identifying osteoporosis and compression fractures. The results of this study suggest the feasibility of obtaining comprehensive information on bone health in subjects undergoing LDCT. INTRODUCTION: Osteoporosis is a prevalent but underdiagnosed disease that increases fracture risk. This study evaluated the utility of vertebral attenuation derived from low-dose chest computed tomography (LDCT) compared to dual-energy x-ray absorptiometry (DXA) for detecting bone fragility. METHODS: A total of 232 subjects (78 men and 154 women) aged above 50 years who underwent both LDCT and DXA within 30 days were evaluated. LDCT-measured bone attenuation in Hounsfield units (HU) of four vertebrae (T4, T7, T10, and L1) was evaluated using volumetric methods for correlation with DXA-measured bone mineral density (BMD) and for the diagnosis of compression fractures, osteoporosis, and low BMD (osteoporosis or osteopenia) in men and women, with DXA measurements as the reference standard. RESULTS: The average attenuation of the four vertebrae showed strong correlation with DXA-measured BMD of the lumbar spine (r = 0.726, p < 0.05). In receiver-operating characteristic (ROC) analyses, the area under the curve (AUC) across LDCT-measured thresholds of the average attenuation to distinguish compression fractures was 0.827, and a threshold of 129.5 HU yielded 90.9 % sensitivity and 64.4 % specificity. Similarly, average attenuation showed high AUCs and good diagnostic performance for detecting osteoporosis and low BMD in both men and women. Among 44 subjects with compression fractures, the average bone attenuation showed strong negative correlation with both the worst fracture grade (r = -0.525, p < 0.05) and cumulative fracture grade score (r = -0.633, p < 0.05). CONCLUSION: LDCT-measured bone attenuation by volumetric methods showed good correlation with BMD measured by DXA and good diagnostic performance for identifying bone fragility.

Challenging the arbitrary cutoff score of 60%: Standard setting evidence from preclinical Operative Dentistry course.

INTRODUCTION: This paper conducted standard setting (SS) (Angoff and Hofstee methods) to determine cutoff scores for summative examinations and to compare the derived passing levels to the existing fixed passing score of 60% in the Faculty of Dentistry at King Abdulaziz University. METHODS: Historic performance data for final examinations in preclinical Operative Dentistry course were used by four raters to conduct both Angoff and Hofstee methods to determine the cut off scores for three academic years (2012, 2013, and 2014). RESULTS: Both methods yielded higher than 60% cut off scores for each year. For the first examination of academic year 2012, the cutoff score was 64.75, while it was 63.5 for year 2013, and 66.75 for the last academic year of 2014. Hofstee scores were 64.5, 65.25, and 62.25 consecutively for years 2012 through 2014. CONCLUSIONS: Using Angoff or Hofstee methods, yielded higher than the fixed 60% passing score currently used by the dental school. The use of Angoff method alone is encouraged as there were limitations to using the Hofstee method to determine the cut off score. This finding provides preliminary support to use evidence-based SS methods to determine the cutoff score for the whole Dentistry program.

A randomised, double-blind, placebo-controlled multi-centre phase III trial of XELIRI/FOLFIRI plus simvastatin for patients with metastatic colorectal cancer.

BACKGROUND: The purpose of this randomised phase III trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3methyglutaryl coenzyme A reductase inhibitor, to XELIRI/FOLFIRI chemotherapy regimens confers a clinical benefit to patients with previously treated metastatic colorectal cancer. METHODS: We undertook a double-blind, placebo-controlled phase III trial of 269 patients previously treated for metastatic colorectal cancer and enrolled in 5 centres in South Korea. Patients were randomly assigned (1:1) to one of the following groups: FOLFIRI/XELIRI plus simvastatin (40 mg) or FOLFIRI/XELIRI plus placebo. The FOLFIRI regimen consisted of irinotecan at 180 mg m(-2) as a 90-min infusion, leucovorin at 200 mg m(-2) as a 2-h infusion, and a bolus injection of 5-FU 400 mg m(-2) followed by a 46-h continuous infusion of 5-FU at 2400 mg m(-2). The XELIRI regimen consisted of irinotecan at 250 mg m(-2) as a 90-min infusion with capecitabine 1000 mg m(-2) twice daily for 14 days. The primary end point was progression-free survival (PFS). Secondary end points included response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: Between April 2010 and July 2013, 269 patients were enrolled and assigned to treatment groups (134 simvastatin, 135 placebo). The median PFS was 5.9 months (95% CI, 4.5-7.3) in the XELIRI/FOLFIRI plus simvastatin group and 7.0 months (95% CI, 5.4-8.6) in the XELIRI/FOLFIRI plus placebo group (P=0.937). No significant difference was observed between the two groups with respect to OS (median, 15.9 months (simvastatin) vs 19.9 months (placebo), P=0.826). Grade⩾3 nausea and anorexia were noted slightly more often in patients in the simvastatin arm compared with with the placebo arm (4.5% vs 0.7%, 3.0% vs 0%, respectively). CONCLUSIONS: The addition of 40 mg simvastatin to the XELIRI/FOLFIRI regimens did not improve PFS in patients with previously treated metastatic colorectal cancer nor did it increase toxicity.

Immune response against 2,4-dinitrofluorobenzene-induced atopic dermatitis-like clinical manifestation is suppressed by spermidine in NC/Nga mice.

Of the biogenic polyamines, spermidine is a natural constituent of living cells and organisms. Spermidine is associated with regulation of cell growth, proliferation and differentiation, and with the suppression of oxidation and inflammation. Atopic dermatitis (AD) is a chronic inflammatory skin disease that has a complex and multiple pathogenesis, which includes genetic abnormality, modified or abnormal immune response and the production of nitric oxide and reactive oxygen species. We investigated whether spermidine can relieve AD-like clinical manifestation induced by the continual application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice. Spermidine at concentrations of 1 or 10 mg/kg reduced increasing ear swelling and attenuated oedema, haemorrhage and hyperkeratosis in AD-like skin lesions. Repetitive application of DNFB induced inflammatory cell infiltration to skin lesions, whereas intraperitoneal injection of spermidine inhibited DNFB-evoked infiltration of eosinophils, mast cells and T lymphocytes. Furthermore, spermidine suppressed mast cell degranulation and production of interferon-gamma by activated CD4(+) T cells in AD-like skin lesions. Spermidine may be a potential therapeutic agent for treatment of AD.

A cross-sectional study to examine the correlation between serum TSH levels and the osteoporosis of the lumbar spine in healthy women with normal thyroid function.

UNLABELLED: We examined the association between serum TSH levels and osteoporosis of the lumbar spine in 756 Korean women aged 65 years or older with normal thyroid function. Low-normal serum TSH levels might be a potential risk factor for the osteoporosis in non-obese elderly women. INTRODUCTION: We aimed to examine the association between serum thyroid-stimulating hormone (TSH) levels and osteoporosis of the lumbar spine in healthy elderly Korean women with normal thyroid function. METHODS: In this cross-sectional study, we evaluated the correlations between serum TSH levels and the osteoporosis of the lumbar spine depending on the body mass index (BMI) in a total of 756 women aged 65 years or older who underwent bone mineral density (BMD) measurement and thyroid function test in a routine health screening examination at our medical institution. RESULTS: After the adjustment of the age and BMI, there was a significant positive correlation between serum TSH level within normal range and the BMD of the lumbar spine (r = 0.165, P < 0.001). In the non-obese elderly women, multivariate-adjusted odds ratios (ORs) for the osteoporosis of the lumbar spine were significantly higher in the 1st and 2nd quartiles of serum TSH levels as compared with their 4th quartile (OR 2.169, 95% CI 1.128-4.171; and OR 2.122, 95% CI 1.123-4.007, respectively). In these women, there were dose-dependent inverse correlations between quartiles of serum TSH levels and the osteoporosis of the lumbar spine (P for trend, 0.008). In the obese women, however, there were no such correlations. CONCLUSIONS: In conclusion, our results suggest that low-normal serum TSH levels might be a potential risk factor for the osteoporosis of the lumbar spine in non-obese elderly women. But further prospective, large-scale, randomized controlled studies are warranted to establish our results.