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Formamidinium lead iodide (FAPbI3) has emerged as one of the most promising perovskite semiconductors for perovskite solar cells (PSCs), demonstrating high power conversion efficiency (PCE) and good stability. However, only a few reports address the scalable processing and fabrication of FAPbI3perovskite solar modules. Here, we report a void-free perovskite-buried interface in p-i-n-based PSCs, which enables us to upscale lab-scale solar cells (<1 cm2) to mini-module dimensions (>10 cm2). An innovative combination of a moderate N2flow during vacuum-assisted growth (VAG) control of the perovskite thin films as well as the employment of MACl as an additive eliminates interfacial voids in blade-coated large-area FAPbI3layers, enabling respective PCEs of 20.0% and 18.3% in blade-coated PSCs (0.105 cm2) and fully scalable modules (aperture area of 12.25 cm2and geometric fill factor of 96.3%). This is a remarkable advance in upscaling FAPbI3-based perovskite photovoltaics.

The internal luminescence quantum efficiency (Qilum) provides an excellent assessment of the optoelectronic quality of semiconductors. To determine Qilumfrom the experimentally accessible external luminescence quantum efficiency (Qelum), it is essential to account for photon recycling, and this requires knowledge of the photon escape probability (p¯e). Here, we establish an analysis procedure based on a curve-fitting model that accurately determines p¯eof perovskite films from photoluminescence (PL) spectra measured with a confocal microscope and an integrating sphere setup. We show that scattering-induced outcoupling of initially trapped PL explains commonly observed red-shifted and broadened PL spectral shapes and leads to p¯ebeing more than a factor of two higher compared with earlier assumptions. Applying our model to CH3NH3PbI3films with exceptionally high Qelumup to 47.4% corrects previous estimates for Qilumof ∼90% to a real benchmark of 78.0% ± 0.5%. Thereby, our study reveals there is beyond a factor of two more scope for reducing non-radiative recombination in perovskite films than previously thought.

ABSTRACTBasal-like triple-negative breast cancers frequently express high levels of c-Myc. This oncoprotein signals to the core cell cycle machinery by impinging on cyclin E. High levels of E-type cyclins (E1 and E2) are often seen in human triple-negative breast tumors. In the current study, we examined the requirement for E-type cyclins in the c-Myc-driven mouse model of breast cancer (MMTV-c-Myc mice). To do so, we crossed cyclin E1- (E1-/-) and E2- (E2-/-) deficient mice with MMTV-c-Myc animals, and observed the resulting cyclin E1-/-/MMTV-c-Myc and cyclin E2-/-/MMTV-c-Myc females for breast cancer incidence. We found that mice lacking cyclins E1 or E2 developed breast cancers like their cyclin Ewild-type counterparts. In contrast, further reduction of the dosage of E-cyclins in cyclin E1-/-E2+/-/MMTV-c-Myc and cyclin E1+/-E2-/-/MMTV-c-Myc animals significantly decreased the incidence of mammary carcinomas, revealing arole for E-cyclins in tumor initiation. We also observed that depletion of E-cyclins in human triple-negative breast cancer cell lines halted cell cycle progression, indicating that E-cyclins are essential for tumor cell proliferation. In contrast, we found that the catalytic partner of E-cyclins, the cyclin-dependent kinase 2 (CDK2), is dispensable for the proliferation of these cells. These results indicate that E-cyclins, but not CDK2, play essential and rate-limiting roles in driving the proliferation of c-Myc overexpressing breast cancer cells.

Unfractionated heparin is the mainstay of anticoagulation during cardiac surgery on cardiopulmonary bypass (CPB) due to its low cost, quick onset, and ease of reversal. Since over 30 years, the activated clotting time (ACT) has been used to assess the level of heparin activity both before and after CPB. We compared two different methods of measuring the ACT: i-STAT, which uses amperometric detection of thrombin cleavage, and Hemochron Jr, which is based on detecting viscoelastic changes in blood. We included 402 patients from three institutions (Papworth Hospital, Cambridge, UK; Groote Schuur, Cape Town, South Africa; University Hospital Basel, Basel, Switzerland) undergoing elective cardiac surgery on CPB in our study. We analyzed duplicate samples on both devices at all standard measuring points during the procedure. The correlation coefficient between two Hemochron and two i-STAT devices was .9165 and .9857, respectively. The within-subject coefficient of variation (WSCV) ranged from 8.2 to 13.6% for the Hemochron and from 4.1 to 9.1% for the i-STAT. We found that the number of occasions where one of the duplicate readings was >1,000 seconds while the other was below or close to the clinically significant threshold of 400 seconds were higher for the Hemochron. We found the i-STAT to systematically return higher measurements. We conclude that the i-STAT provides a more reliable test for heparin activity and assesses safe anticoagulation during cardiac surgery on pump. The fact the that the i-STAT reads higher than the Hemochron leads to the recommendation to validate the methods against each other before changing devices.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with limited treatment options. To characterize TNBC heterogeneity, we defined transcriptional, epigenetic, and metabolic subtypes and subtype-driving super-enhancers and transcription factors by combining functional and molecular profiling with computational analyses. Single-cell RNA sequencing revealed relative homogeneity of the major transcriptional subtypes (luminal, basal, and mesenchymal) within samples. We found that mesenchymal TNBCs share features with mesenchymal neuroblastoma and rhabdoid tumors and that the PRRX1 transcription factor is a key driver of these tumors. PRRX1 is sufficient for inducing mesenchymal features in basal but not in luminal TNBC cells via reprogramming super-enhancer landscapes, but it is not required for mesenchymal state maintenance or for cellular viability. Our comprehensive, large-scale, multiplatform, multiomics study of both experimental and clinical TNBC is an important resource for the scientific and clinical research communities and opens venues for future investigation.

Supplemental Digital Content is available in the text.Published ahead of print May 19, 2017.

Supplemental Digital Content is available in the text.

Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12causes rapid bone marrow aplasia leading to acute lethality. Deleting other members of the Mediator kinase module does not affect HSC function, suggesting kinase-independent roles of MED12. MED12 deletion destabilizes P300 binding at lineage-specific enhancers, resulting in H3K27Ac depletion, enhancer de-activation, and consequent loss of HSC stemness signatures. As MED12 mutations have been described recently in blood malignancies, alterations in MED12-dependent enhancer regulation may control both physiological and malignant hematopoiesis.

Hyporesponsiveness by phagocytes is a well-known phenomenon in sepsis that is frequently induced by low-dose endotoxin stimulation of Toll-like receptor 4 (TLR4) but can also be found under sterile inflammatory conditions. We now demonstrate that the endogenous alarmins MRP8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a TLR4-dependent manner that results in enhanced survival to septic shock in mice. During sterile inflammation, polytrauma and burn trauma patients initially present with high serum concentrations of myeloid-related proteins (MRPs). Human neonatal phagocytes are primed for hyporesponsiveness by increased peripartal MRP concentrations, which was confirmed in murine neonatal endotoxinemia in wild-type and MRP14−/−mice. Our data therefore indicate that alarmin-triggered phagocyte tolerance represents a regulatory mechanism for the susceptibility of neonates during systemic infections and sterile inflammation.

Volatile anesthetics provide myocardial preconditioning in coronary surgery patients. We hypothesized that sevoflurane compared with propofol reduces the incidence of myocardial ischemia in patients undergoing major noncardiac surgery.

To confirm the reliability and applicability of the Polymyalgia Rheumatica Disease Activity Score (PMR‐AS), and to establish a threshold for remission.First, 78 patients with PMR (50 women/28 men, mean age 65.97 years) were enrolled in a cross‐sectional evaluation. The PMR‐AS, patient's satisfaction with disease status (PATSAT; range 1–5), erythrocyte sedimentation rate (ESR; first hour), and a visual analog scale of patients' general health assessment (VAS patient global; range 0–100) were recorded. Subsequently, another 39 PMR patients (24 women/15 men, mean age 68.12 years) were followed longitudinally. Relationships between the PMR‐AS, PATSAT, ESR, and VAS patient global were analyzed by the Kruskal‐Wallis test, Spearman's rank correlation, and kappa statistics. PMR‐AS values in patients with a PATSAT score of 1 and a VAS patient global <10 formed the basis to establish a remission threshold.PMR‐AS values were significantly related to PATSAT (P < 0.001), VAS patient global (P < 0.001), and ESR (P < 0.01). PATSAT and VAS patient global were reasonably different (κ = 0.226). The median PMR‐AS score in patients with PATSAT score 1 and VAS patient global <10 was 0.7 (range 0–3.3), and the respective 75th percentile was 1.3. To enhance applicability, a range from 0 to 1.5 was proposed to define remission in PMR. The median ESR in these patients was 10 mm/hour (range 3–28), indicating external validity.We demonstrated the reliability, validity, and applicability of the PMR‐AS in daily routine. Moreover, we proposed a remission threshold (0–1.5) founded on patient‐dependent parameters.

To assess the factorial structure of the Disease Activity Score including a 28‐joint count (DAS28) if applied in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).DAS28 values from 85 consecutive PsA outpatients and 2 RA patient cohorts comprising 85 patients each were compared. The first RA cohort (RA1) consisted of age‐ and sex‐matched patients seen during the same period as the patients with PsA. The first 85 RA outpatients from September 2003 were included in the second cohort (RA2). Item weighting, factor loading, and internal consistency were assessed by factor analysis, principal component analysis, and calculation of Cronbach's alpha.The mean ± SD DAS28 scores of patients in the PsA, RA1, and RA2 cohorts were 3.2 ± 1.31, 3.21 ± 1.45, and 3.79 ± 1.44, respectively. A significant difference between the PsA and RA2 cohorts was found for DAS28 (P = 0.0063), swollen joint count (P = 0.007), and patient's global assessment (P < 0.001), but not for erythrocyte sedimentation rate. Internal consistency of the DAS28 in patients with PsA was considerably lower, item weighting showed remarkable differences, and factor analysis revealed that the DAS28 constitutes a bidimensional instrument in patients with PsA, whereas in both RA cohorts it appeared to be monodimensional.With respect to its statistical properties, the DAS28 proved to be considerably different in PsA compared with RA. Therefore its application for disease activity assessment in patients with PsA cannot be recommended without a formal validation procedure.

AbstractObjective:To describe the derivation and validation of a pulmonary tuberculosis (TB) prediction model that would enable early discontinuation of unnecessary respiratory isolation.Design:Patients placed in isolation for suspected pulmonary TB were studied retrospectively (derivation cohort) and prospectively (validation cohort). Independent predictors of pulmonary TB in the derivation cohort (January 1992-March 1994) were identified by retrospective analysis. Predictors in the model were assigned weights on the basis of the results of the multivariate analysis in order to quantitate the risk of TB in an individual patient. The prospective validation consisted of application of the model to patients placed in isolation during the period April 1994 to June 1995. The predictability of the model in the derivation and validation cohorts was evaluated using receiver operating characteristics (ROC), curve analysis, and calculation of the area under the ROC curve (AUC).Setting:A university-affiliated, urban, public hospital with a large population of prison inmates and patients with human immunodeficiency virus infection.Interventions:Prospective application of the prediction model to patients placed in isolation during the validation period.Results:Four factors were found to be independent predictors of pulmonary TB among 296 isolation episodes in the derivation cohort: positive acid-fast sputum smear (odds ratio [OR], 5.8; 95% confidence interval [CI95], 3.0-11.0; weight=3 points), localized chest radiograph findings (OR, 2.5; CI95,1.3-4.9; weight=2 points), residence in a correctional facility (OR, 2.3; CI95, 1.2-4.4; weight=2 points), and history of weight loss (OR, 1.8; CI95, 1.0-3.2; weight=1 point). Infection control practitioners applied the model prospectively to 220 isolation episodes. The mean (土SE) AUCs of the ROC curve for the derivation and validation cohorts were not significantly different (.86±.04 vs.86±.07; P=.90). There was a significant decline in the mean duration of isolation from the onset of an automatic TB isolation policy in August 1992 to the end of the study (P=.045 by analysis of variance).Conclusions:A pulmonary TB prediction model was derived and validated prospectively in a hospital with a moderately high prevalence of TB. The model quantitated the risk of TB in an individual patient and aided infection control practitioners and primary-care physicians in their decisions to discontinue isolation during the validation period. Utilization of the model was responsible, in part, for a decrease in the mean duration of isolation during the study period. Although the model may not have general applicability due to the uniqueness of the patient population studied, this study illustrates how prediction models can be developed and used effectively to deal with a clinical problem.