Transfer of Large-Scale Two-Dimensional Semiconductors:Challenges and Developments

Two-dimensional (2D) materials offer opportunities to explore both fundamental science and applications in the limit of atomic thickness. Beyond the prototypical case of graphene, other 2D materials have recently come to the fore. Of particular technological interest are 2D semiconductors, of which the family of materials known as the group-VI transition metal dichalcogenides (TMDs) has attracted much attention. The presence of a bandgap allows for the fabrication of high on-off ratio transistors and optoelectronic devices, as well as valley/spin polarized transport. The technique of chemical vapour deposition (CVD) has produced high-quality and contiguous wafer-scale 2D films, however, they often need to be transferred to arbitrary substrates for further investigation. In this Review, the various transfer techniques developed for transferring 2D films will be outlined and compared, with particular emphasis given to CVD-grown TMDs. Each technique suffers undesirable process-related drawbacks such as bubbles, residue or wrinkles, which can degrade device performance by for instance reducing electron mobility. This Review aims to address these problems and provide a systematic overview of key methods to characterize and improve the quality of the transferred films and heterostructures. With the maturing technological status of CVD-grown 2D materials, a robust transfer toolbox is vital

Survival of adults with acute lymphoblastic leukemia in Germany and the United States.

BACKGROUND: Adulthood acute lymphoblastic leukemia (ALL) is a rare disease. In contrast to childhood ALL, survival for adults with ALL is poor. Recently, new protocols, including use of pediatric protocols in young adults, have improved survival in clinical trials. Here, we examine population level survival in Germany and the United States (US) to gain insight into the extent to which changes in clinical trials have translated into better survival on the population level. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients age 15-69 diagnosed with ALL were included. Period analysis was used to estimate 5-year relative survival (RS). RESULTS: Overall 5-year RS was estimated at 43.4% for Germany and 35.5% for the US (p = 0.004), with a decrease in survival with increasing age. Survival was higher in Germany than the US for men (43.6% versus 37.7%, p = 0.002) but not for women (42.4% versus 40.3%, p\u3e0.1). Five-year RS estimates increased in Germany and the US between 2002 and 2006 by 11.8 and 7.3 percent units, respectively (p = 0.02 and 0.04, respectively). CONCLUSIONS: Survival for adults with ALL continues to be low compared with that for children, but a substantial increase in 5-year survival estimates was seen from 2002 to 2006 in both Germany and the US. The reasons for the survival differences between both countries require clarification

Outcome prediction in aneurysmal subarachnoid hemorrhage: a comparison of machine learning methods and established clinico-radiological scores

Reliable prediction of outcomes of aneurysmal subarachnoid hemorrhage (aSAH) based on factors available at patient admission may support responsible allocation of resources as well as treatment decisions. Radiographic and clinical scoring systems may help clinicians estimate disease severity, but their predictive value is limited, especially in devising treatment strategies. In this study, we aimed to examine whether a machine learning (ML) approach using variables available on admission may improve outcome prediction in aSAH compared to established scoring systems. Combined clinical and radiographic features as well as standard scores (Hunt & Hess, WFNS, BNI, Fisher, and VASOGRADE) available on patient admission were analyzed using a consecutive single-center database of patients that presented with aSAH (n = 388). Different ML models (seven algorithms including three types of traditional generalized linear models, as well as a tree bosting algorithm, a support vector machine classifier (SVMC), a Naive Bayes (NB) classifier, and a multilayer perceptron (MLP) artificial neural net) were trained for single features, scores, and combined features with a random split into training and test sets (4:1 ratio), ten-fold cross-validation, and 50 shuffles. For combined features, feature importance was calculated. There was no difference in performance between traditional and other ML applications using traditional clinico-radiographic features. Also, no relevant difference was identified between a combined set of clinico-radiological features available on admission (highest AUC 0.78, tree boosting) and the best performing clinical score GCS (highest AUC 0.76, tree boosting). GCS and age were the most important variables for the feature combination. In this cohort of patients with aSAH, the performance of functional outcome prediction by machine learning techniques was comparable to traditional methods and established clinical scores. Future work is necessary to examine input variables other than traditional clinico-radiographic features and to evaluate whether a higher performance for outcome prediction in aSAH can be achieved

Controlling genetic heterogeneity in gene-edited hematopoietic stem cells by single-cell expansion

Gene editing using engineered nucleases frequently produces unintended genetic lesions in hematopoietic stem cells (HSCs). Gene-edited HSC cultures thus contain heterogeneous populations, the majority of which either do not carry the desired edit or harbor unwanted mutations. In consequence, transplanting edited HSCs carries the risks of suboptimal efficiency and of unwanted mutations in the graft. Here, we present an approach for expanding gene-edited HSCs at clonal density, allowing for genetic profiling of individual clones before transplantation. We achieved this by developing a defined, polymer-based expansion system and identifying long-term expanding clones within the CD201 +CD150 +CD48 -c-Kit +Sca-1 +Lin - population of precultured HSCs. Using the Prkdc scid immunodeficiency model, we demonstrate that we can expand and profile edited HSC clones to check for desired and unintended modifications, including large deletions. Transplantation of Prkdc-corrected HSCs rescued the immunodeficient phenotype. Our ex vivo manipulation platform establishes a paradigm to control genetic heterogeneity in HSC gene editing and therapy

The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies

Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5–98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1–16 h after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS–MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle

Survival of endometrial cancer patients in Germany in the early 21st century: a period analysis by age, histology, and stage

<p>Abstract</p> <p>Background</p> <p>Population-based studies on endometrial cancer providing survival estimates by age, histology, and stage have been sparse. We aimed to derive most up-to-date and detailed survival estimates for endometrial cancer patients in Germany.</p> <p>Methods</p> <p>We used a pooled German national dataset including data from 11 cancer registries covering a population of 33 million people. 30,906 patients diagnosed with endometrial cancer in 1997-2006 were included. Period analysis was performed to calculate 5-year relative survival (RS) in 2002-2006. Trends in survival between 2002 and 2006 were examined using model-based period analysis. Age-adjustment was performed using five age groups (15-44, 45-54, 55-64, 65-74, and 75+ years).</p> <p>Results</p> <p>Overall, age-adjusted 5-year relative survival in 2002-2006 was 81%. A moderate age gradient was observed, with 5-year RS decreasing from 90% in the age group 15-49 years to 75% in the age group 70+ years. Furthermore prognosis varied strongly by histologic subtypes and stage, with age-adjusted 5-year RS ranging from 43% (for sarcoma) to 94% (for squamous metaplasia), and reaching 91% for localized, 51% for regional, and 20% for distant stage. Except for age group 65-74 years, no significant improvement in survival was seen during the recent 5-year period under investigation.</p> <p>Conclusion</p> <p>In this comprehensive population-based survival analysis of patients with endometrial cancer from Germany, prognosis of endometrial cancer moderately varied by age, and strongly varied by histology and stage. While prognosis is rather good overall, further improvement in 5-year relative survival of endometrial cancer patients has been stagnating in the early 21^stcentury.</p

Birth size and gestational age in opposite-sex twins as compared to same-sex twins : An individual-based pooled analysis of 21 cohorts

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95%Cl 18 to 45) heavier and 0.16 cm (95%CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95%Cl -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister.Peer reviewe

Association between birthweight and later body mass index : an individual-based pooled analysis of 27 twin cohorts participating in the CODATwins project

Background: There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses. Results: At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m(2) higher BMI (P <0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m(2) per kg birthweight, P <0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood. Conclusions: These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood.Peer reviewe