Large tunable valley splitting in edge-free graphene quantum dots on boron nitride

Coherent manipulation of binary degrees of freedom is at the heart of modern quantum technologies. Graphene offers two binary degrees: the electron spin and the valley. Efficient spin control has been demonstrated in many solid state systems, while exploitation of the valley has only recently been started, yet without control on the single electron level. Here, we show that van-der Waals stacking of graphene onto hexagonal boron nitride offers a natural platform for valley control. We use a graphene quantum dot induced by the tip of a scanning tunneling microscope and demonstrate valley splitting that is tunable from -5 to +10 meV (including valley inversion) by sub-10-nm displacements of the quantum dot position. This boosts the range of controlled valley splitting by about one order of magnitude. The tunable inversion of spin and valley states should enable coherent superposition of these degrees of freedom as a first step towards graphene-based qubits

Towards environmentally sustainable human behaviour: targeting non-conscious and conscious processes for effective and acceptable policies.

Meeting climate change targets to limit global warming to 2°C requires rapid and large reductions in demand for products that most contribute to greenhouse gas (GHG) emissions. These include production of bulk materials (e.g. steel and cement), energy supply (e.g. fossil fuels) and animal source foods (particularly ruminants and their products). Effective strategies to meet these targets require transformative changes in supply as well as demand, involving changes in economic, political and legal systems at local, national and international levels, building on evidence from many disciplines. This paper outlines contributions from behavioural science in reducing demand. Grounded in dual-process models of human behaviour (involving non-conscious and conscious processes) this paper considers first why interventions aimed at changing population values towards the environment are usually insufficient or unnecessary for reducing demand although they may be important in increasing public acceptability of policies that could reduce demand. It then outlines two sets of evidence from behavioural science towards effective systems-based strategies, to identify interventions likely to be effective at: (i) reducing demand for products that contribute most to GHG emissions, mainly targeting non-conscious processes and (ii) increasing public acceptability for policy changes to enable these interventions, targeting conscious processes.This article is part of the themed issue 'Material demand reduction'

Pheochromocytoma presenting as recurrent urinary tract infections : a case report

<p>Abstract</p> <p>Introduction</p> <p>Pheochromocytomas are rare, potentially fatal, neuroendocrine tumors of the adrenal medulla or extra-adrenal paraganglia. Their clinical presentation varies greatly from the classic triad of episodic headache, diaphoresis and tachycardia to include a spectrum of non-specific symptomatology.</p> <p>Case presentation</p> <p>A 43-year-old Caucasian woman was referred to us from primary care services with a three-month history of recurrent urinary tract infections on a background of hypertension, latent autoimmune diabetes of adulthood and autoimmune hypothyroidism. At 38 years she required insulin therapy. Despite medication compliance and dietary control, she reported a recent history of increased insulin requirements and uncontrolled hypertension with concomitant recurrent urinary tract infections. A renal ultrasound examination, to rule out underlying renal pathology, revealed an incidental 8cm right adrenal mass of both solid and cystic components. A subsequent computed tomography of her abdomen and pelvis confirmed a solid heterogeneous mass consistent with a pheochromocytoma. There were no other features suggestive of multiple endocrine neoplasia. Urinary collection over 24 hours revealed grossly elevated levels of catecholamines and metabolites. Following an open right adrenalectomy, our patient's insulin requirements were significantly reduced and her symptoms resolved. Two weeks post-operatively, an iodine-131-metaiodobenzylguanidine scintigraphy was negative for residual tumor and metastatic disease. Urinary catecholamine and metabolite concentrations were within the normal range at a follow-up six months later.</p> <p>Conclusion</p> <p>Pheochromocytoma is a rare catecholamine-producing tumor requiring a high index of suspicion for early diagnosis. Our case report serves to highlight the importance of considering pheochromocytoma as a differential diagnosis in the atypical setting of recurrent urinary tract infections and concomitant autoimmune disease.</p

Quality of Life in Men With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a disorder of adrenal steroid biosynthesis, leading to hypocortisolism, hypoaldosteronism, and hyperandrogenism. Impaired quality of life (QoL) has been demonstrated in women with CAH, but data on men with CAH are scarce. We hypothesized that disease severity and poor treatment control are inversely associated with QoL. In this study, 109 men (16-68 years) with 21OHD were included. The WHOQOL-BREF questionnaire was used to measure self-reported QoL domain scores on a 0-100 scale, where higher scores reflect better QoL. QoL domain scores were compared to published data on healthy and chronically ill reference populations from France, Germany, the Netherlands, and the United Kingdom. Differences in QoL scores among groups of disease severity and treatment control were tested within the study population. Overall, the men with CAH in this study appeared to rate their QoL as good. Median domain scores were 78.6 (IQR: 67.9-85.7) for physical health, 79.2 (IQR: 66.7-87.5) for psychological health, 75.0 (IQR: 58.3-83.3) for social relationships, and 81.3 (IQR: 71.9-90.6) for environment. In general, these scores were similar to WHOQOL-BREF domain scores in healthy references and higher compared to chronically ill reference populations. The domain scores did not differ among genotype groups, but patients with undertreatment or increased 17-hydroxyprogestrone concentrations scored higher on several QoL domains (p<0.05). Patients treated with dexamethasone or prednisone scored higher on the physical health, psychological health, and social relationships domains, but not on the environmental domain. In conclusion, QoL domain scores appeared to be comparable to healthy reference populations and higher compared to patients with a chronic illness. QoL was not influenced by genotype, but undertreatment and use of dexamethasone or prednisone were associated with higher QoL

Modelling adrenal steroid profiles to inform monitoring guidance in congenital adrenal hyperplasia

Background: There is no consensus on how to monitor adrenal androgens in Congenital Adrenal Hyperplasia (CAH).Methods: Modelling of serum and salivary steroid profiles in healthy participants and patients with CAH randomised to either standard treatment or modified-release hydrocortisone hard capsules (MRHC).Findings: Changes in serum 17-hydroxyprogesterone (17OHP) and androstenedione (A4) paralleled each other in healthy participants (n = 19) and patients with CAH (n = 122). However, healthy participants had similar absolute levels of 17OHP and A4 whereas patients with CAH had proportionally higher levels of 17OHP. Cross-correlation showed no lag between serum 17OHP and A4. In CAH, Bayesian multiple change point analysis converged on a 17OHP of 4.5 nmol/l below which in proportion to 17OHP the A4 is lower. Patients on standard treatment had a morning peak in 17OHP and A4 whereas patients on MRHC had relatively flat profiles. Salivary androgens including 11-ketotestosterone correlated with serum 17OHP and A4 in female patients (r = 0.7 to 0.9).Interpretation: In CAH, elevated 17OHP drives the production of A4. High A4 reflects poor control, but low A4 does not indicate overtreatment. Accepting 17OHP is higher than A4, both measurements give similar reflection of control, and a 17OHP &lt;38 nmol/l (1250 ng/dl) was associated with an A4 in the normal range &lt;5 nmol/l (143 ng/dl) in 95% of patients and in clinical trials was used to define good control. On MRHC, which controls androgen levels over 24 h, a single sample of 17OHP and/or A4 can be used to monitor control. Salivary measurements reflect similar results to serum

Long-term outcomes in patients with congenital adrenal hyperplasia treated with hydrocortisone modified-release hard capsules

Background Hydrocortisone modified-release hard capsules (MRHC, development name Chronocort) replace the physiological overnight cortisol rise and improve the biochemical control of congenital adrenal hyperplasia (CAH). Aim This study aims to evaluate long-term safety, tolerability, and efficacy of MRHC. Methods This is an open-label follow-on study. Results Ninety-one patients with classic CAH, mean age 37 years, 68% female, 32% male, entered the study and 22 discontinued. Median treatment duration was 4 years (range 0.2-5.8). Median hydrocortisone dose at study entry was 30 mg/day and reduced to 20 mg/day after 24 weeks and stayed stable thereafter until 48 months (P < .0001). Disease control improved on MRHC for the steroid disease markers serum 17-hydroxyprogesterone (17OHP) (P < .03) and androstenedione (A4) (P < .002). After 4 years, the majority of patients had a 17OHP < 4-fold upper limit of normal (ULN) (71%) and an A4 <ULN (90%). Measurement of 17OHP and A4 at 09:00 h and 13:00 h gave similar results. Of the 37 women < 50 years of age who were not on contraceptives over the whole study period, 5 became pregnant (13.5%). Of the men, 13.8% (4/29) had a partner pregnancy. Seven patients had an adrenal crisis with 1 patient reporting 8 of these giving an incidence of 3.9 crises per 100 patient years. Conclusions Modified-release hard capsule treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical control associated with fertility. Biochemical control could be reliably monitored by a single blood sample taken between 09:00 and 13:00 h. The incidence of adrenal crises was below that reported previously in patients with CAH

Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement

IMPORTANCE A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose. OBJECTIVE To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG). EVIDENCE REVIEW Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0. FINDINGS The new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma. CONCLUSIONS AND RELEVANCE The implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients