Defect calculations using a combined SCAN and hybrid functional in γ-CsPbI3.

γ-CsPbI3 solar cells have achieved promising efficiencies, yet the quantitative understanding of their defect properties is limited due to the severe computational challenges when using hybrid functionals. We have discovered an algorithm to improve the convergence speed through a combination of structural relaxation with a strongly constrained and appropriately normed (SCAN) Meta-generalized-gradient approximation (Meta-GGA) functional and further ionic and electronic calculations with the Heyd-Scuseria-Ernzerhof (HSE) hybrid functional. The static HSE calculations with SCAN results as inputs are qualitatively reliable in defect calculations, different from one-ionic step HSE calculations based on GGA inputs. Contradictory to previous GGA defect results, a suppressed bipolar conductivity by p-type VCs and VPb, and n-type CsI is found. Additionally, stable bipolar defects Iint and CsPb, with features of strong bond orbital coupling or structural deformation, detrimentally serve as carrier-traps. This strengthened bond orbital coupling in γ-CsPbI3 causes more defect charge states than organic perovskites with larger lattice constants.

Randomized Phase 2 Trial of Abiraterone Acetate Plus Prednisone, Degarelix, or the Combination in Men with Biochemically Recurrent Prostate Cancer After Radical Prostatectomy.

BACKGROUND: Phase 2 trial endpoints that can be utilized in high-risk biochemical recurrence (BCR) after prostatectomy as a way of more rapidly identifying treatments for phase 3 trials are urgently needed. The efficacy of abiraterone acetate plus prednisone (AAP) in BCR is unknown. OBJECTIVE: To compare the rates of complete biochemical responses after testosterone recovery after 8 mo of AAP and degarelix, a gonadotropin-releasing hormone antagonist, alone or in combination. DESIGN SETTING AND PARTICIPANTS: Patients with BCR (prostate-specific antigen [PSA] ≥1.0 ng/ml, PSA doubling time ≤9 mo, no metastases on standard imaging, and testosterone ≥150 ng/dl) after prostatectomy (with or without prior radiotherapy) were included in this study. INTERVENTION: Patients were randomized to AAP (arm 1), AAP with degarelix (arm 2), or degarelix (arm 3) for 8 mo, and monitored for 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was undetectable PSA with testosterone >150 ng/dl at 18 mo. Secondary endpoints were undetectable PSA at 8 mo and time to testosterone recovery. RESULTS AND LIMITATIONS: For the 122 patients enrolled, no difference was found between treatments for the primary endpoint (arm 1: 5.1% [95% confidence interval {CI}: 1-17%], arm 2: 17.1% [95% CI: 7-32%], arm 3: 11.9% [95% CI: 4-26%]; arm 1 vs 2, p = 0.93; arm 2 vs 3, p = 0.36). AAP therapy showed the shortest median time to testosterone recovery (36.0 wk [95% CI: 35.9-36.1]) relative to degarelix (52.9 wk [95% CI: 49.0-56.0], p < 0.001). Rates of undetectable PSA at 8 mo differed between AAP with degarelix and degarelix alone (p = 0.04), but not between AAP alone and degarelix alone (p = 0.12). Limitations of this study include a lack of long-term follow-up. CONCLUSIONS: Rates of undetectable PSA levels with testosterone recovery were similar between arms, suggesting that increased androgen suppression with AAP and androgen deprivation therapy (ADT) is unlikely to eradicate recurrent disease compared with ADT alone. PATIENT SUMMARY: We evaluated the use of abiraterone acetate plus prednisone (AAP) and androgen deprivation therapy (ADT), AAP alone, or ADT alone in men with biochemically recurrent, nonmetastatic prostate cancer. While more men who received the combination had an undetectable prostate-specific antigen (PSA) level at 8 mo on treatment, once men came off treatment and testosterone level rose, there was no difference in the rates of undetectable PSA levels. This suggests that the combination is not able to eradicate disease any better than ADT alone.

First case of neurofibromatosis with posterior reversible encephalopathy syndrome showing spinal cord involvement.

Posterior reversible encephalopathy syndrome (PRES) is a well-documented pathology of the brain in systemic upsets. Majority of PRES cases present with edema in the cerebrum, most commonly in the territory of posterior circulation. It has been reported to show spinal cord involvement in a rare subgroup known as PRES with spinal cord involvement (PRES-SCI), with very limited existing literature even in adult patients. Our institution recently encountered a pediatric case with neurofibromatosis type I (NF 1) showing PRES with extensive reversible spinal cord changes. This case illustrates the features of this rare entity in the pediatric group of patients, and is the first reported case in NF 1 patients.

Non-invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological-pathological correlation analysis.

OBJECTIVES: To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. METHODS: Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. RESULTS: A total of 40 elastography scans were carried out (median creatinine 172.5 µmol/L [interquartile range 133.8-281.8 µmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8-25.7 kPa] vs 22.3 kPa [interquartile range 19.0-26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7-18.0 kPa] vs 15.6 kPa [interquartile range 14.4-18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70-0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78-0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61-0.89), 0.85 (95% CI 0.75-0.95) and 0.65 (95% CI 0.53-0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively. CONCLUSIONS: Shear wave elastography can be used as a non-invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.

Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer.

BACKGROUND: This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer. PATIENTS AND METHODS: A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m2; 12 patients); every 2 weeks (120, 168, 236, and 330mg/m2; 15 patients); every 3 weeks (330 and 426mg/m2; 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m2; 17 patients). The primary efficacy endpoint was a sustained ≥50% decline from baseline prostate-specific antigen (PSA) without evidence of disease progression. Toxicity, pharmacokinetics, immunogenicity, and antitumor activity were assessed. RESULTS: Neurotoxicity was dose-limiting. Overall, 44 patients (71%) exhibited peripheral neuropathy: 6 (10%) had grade 3/4. Neurotoxicity rates remained high despite increasing the dosing interval to 3 (13 of 14; one grade 3) and 6 weeks (16 of 17; three grade 3). MLN2704 pharmacokinetics were dose-linear. Rapid deconjugation of DM1 from the conjugated antibody was seen. In all, 5 patients (8%) experienced ≥50% decline in PSA; 5 (8%) had PSA stabilization lasting≥90 days. Only 2 of 35 patients on the 3- and 6-week schedules achieved a PSA decline of >50%. CONCLUSIONS: MLN2704 has limited activity in metastatic castration-resistant prostate cancer. Disulfide linker lability and rapid deconjugation lead to neurotoxicity and a narrow therapeutic window.

Chinese older adults' Internet use for health information.

Technological advancement benefits Internet users with the convenience of social connection and information search. This study aimed at investigating the predictors of Internet use to search for online health information among Chinese older adults. The Technology Acceptance Model (TAM) was applied to examine the predictiveness of perceived ease of use, perceived usefulness, and attitudes toward Internet use on behavioral intention to search for health information online. Ninety-eight Chinese older adults were recruited from an academic institute for older people and community centers. Frequency of Internet use and physical and psychological health were also assessed. Results showed that perceived ease of use and attitudes significantly predicted behavioral intention of Internet use. The potential influences of traditional Chinese values and beliefs in health were also discussed.

Isolated femoral osseous megalymphatics with chylous reflux: case report and review of the literature.

We report here the clinical and imaging findings of marked dilatation of the intraosseous lymphatic vessels, "megalymphatics," with chylous reflux presenting with pain and extensive lytic changes in a femoral bone of a child. Multimodality imaging findings, including radiographs, magnetic resonance imaging, ultrasound, scintigraphy and percutaneous osseous lymphangiography are described.

PDZ-domain containing-2 (PDZD2) drives the maturity of human fetal pancreatic progenitor-derived islet-like cell clusters with functional responsiveness against membrane depolarization.

We recently reported the isolation and characterization of a population of pancreatic progenitor cells (PPCs) from early trimester human fetal pancreata. The PPCs, being the forerunners of adult pancreatic cell lineages, were amenable to growth and differentiation into insulin-secreting islet-like cell clusters (ICCs) upon stimulation by adequate morphogens. Of note, a novel morphogenic factor, PDZ-domain containing-2 (PDZD2) and its secreted form (sPDZD2) were ubiquitously expressed in the PPCs. Our goals for this study were to evaluate the potential role of sPDZD2 in stimulating PPC differentiation and to establish the optimal concentration for such stimulation. We found that 10(-9)M sPDZD2 promoted PPC differentiation, as evidenced by the upregulation of the pancreatic endocrine markers (PDX-1, NGN3, NEURO-D, ISL-1, NKX 2.2, NKX 6.1) and INSULIN mRNA. Inhibited endogenous production of sPDZD2 suppressed expression of these factors. Secreted PDZD2 treatment significantly elevated the C-peptide content of the ICCs and increased the basal rate of insulin secretion. However, they remained unresponsive to glucose stimulation, reflected by a minimal increase in GLUT-2 and GLUCOKINASE mRNA expression. Interestingly, sPDZD2 treatment induced increased expression of the L-type voltage-gated calcium channel (Ca(v)1.2) in the ICCs, triggering calcium ion influx under KCl stimulation and conferring an ability to secrete insulin in response to KCl. Pancreatic progenitor cells from 10- and 13-week fetal pancreata showed peak expression of endogenous sPDZD2, implying that sPDZD2 has a specific role in islet development during the first trimester. In conclusion, our data suggest that sPDZD2 promotes functional maturation of human fetal PPC-derived ICCs, thus enhancing its transplanting potentials.

Stent restenosis in a Chinese population.

BACKGROUND: Stents are now widely used in Hong Kong and China and there is a clinical impression that restenosis is less common because of the lower prevalence of coronary artery disease and associated risk factors in the Chinese. However, there are no published data on angiographic stent restenosis rates in Chinese patients. METHOD: In a prospective study of 114 consecutive Chinese patients who underwent coronary stenting, quantitative coronary analyses were made at the time of stent implantation and subsequently at 6 months post-stenting (n = 97). RESULTS: At 6 months, restenosis (> or = 50% diameter stenosis in the dilated segment) was present in 42 (43.3%) of the 97 patients and 54 (33.5%) of the total 161 lesions stented. Vessel reference diameter (VRD) of < 3 mm and stented length of > or = 18 mm were associated with higher restenosis rates (36% and 38%). Compared to those without, those with restenosis had a greater residual stenosis of 16.53+/-11.54% and smaller final minimal luminal diameter (MLD) of 2.41+/-0.49 mm, (p < 0.01 and p < 0.008 respectively). Standard coronary risk factors were not associated with a higher rate of restenosis. Lesion morphology was significantly associated with restenosis. CONCLUSION: Coronary stenting in Hong Kong Chinese patients is associated with a restenosis rate comparable to that demonstrated in previously published trials from populations in the West.

Recanalization of chronic total occlusion after conventional guidewire failure: guided by optical coherent reflectometry and facilitated by radiofrequency energy ablation.

The success rate of percutaneous recanalization of chronic total occlusion remains low. The Safe-Cross wire, which utilizes the principle of optical coherent reflectometry for guidance and has the ability to deliver radiofrequency energy for tissue ablation, was evaluated in 21 patients. This wire was used only after conventional guidewire failure, except in 4 patients who had failed an interventional procedure 3 months to 2 years previously. Conventional guidewires were successful in 9, and the Safe-Cross wire was successful in 10 of the remaining 12, including those 4 with a failed previous attempt. The total success rate was 90% (19/21 patients). Technological improvement in the steerability of the Safe-Cross wire may help to improve the success rate further.

Phase II study of docetaxel and epirubicin in Chinese patients with metastatic breast cancer.

The efficacy and safety of docetaxel-epirubicin chemotherapy in the treatment of metastatic breast cancer was investigated in Chinese women. Three-weekly cycles comprised epirubicin 75 mg/m2 i.v. followed 1 h later by docetaxel 75 mg/m2 i.v. After 3 cycles, responding patients received a further 3 cycles, followed by 3 cycles of docetaxel alone. Forty-six patients entered the study, of whom 37% had received prior adjuvant chemotherapy. Three patients withdrew due to toxicity and were not evaluable for response. There were five complete responses and 31 partial responses, giving an overall response rate of 83.7% (95% CI 72.7-94.8%). The median time to progression was 10.96 months (95% CI 7.76-12.86) and median survival was 24.2 months (95% CI 16.6-). The most common grade 3/4 adverse events were neutropenia (96% of patients) and neutropenia with fever (39%). Hepatotoxicity occurred in six patients, two being attributable to hepatitis B virus reactivation. No patients suffered grade 3/4 cardiac toxicity and there were no treatment-related mortalities. Quality of life aspects deteriorated after 3 cycles, but there was a trend towards improved emotional aspects after 9 cycles. We conclude that docetaxel-epirubicin chemotherapy is highly effective for recurrent metastatic/locoregional breast cancer, with myelosuppression being the main toxicity.