Observation of Kekulé vortices around hydrogen adatoms in graphene.

Fractional charges are one of the wonders of the fractional quantum Hall effect. Such objects are also anticipated in two-dimensional hexagonal lattices under time reversal symmetry-emerging as bound states of a rotating bond texture called a Kekulé vortex. However, the physical mechanisms inducing such topological defects remain elusive, preventing experimental realization. Here, we report the observation of Kekulé vortices in the local density of states of graphene under time reversal symmetry. The vortices result from intervalley scattering on chemisorbed hydrogen adatoms. We uncover that their 2π winding is reminiscent of the Berry phase π of the massless Dirac electrons. We can also induce a Kekulé pattern without vortices by creating point scatterers such as divacancies, which break different point symmetries. Our local-probe study thus confirms point defects as versatile building blocks for Kekulé engineering of graphene's electronic structure.

Atomic-Layer Controlled Transition from Inverse Rashba-Edelstein Effect to Inverse Spin Hall Effect in 2D PtSe2 Probed by THz Spintronic Emission.

2D materials, such as transition metal dichalcogenides, are ideal platforms for spin-to-charge conversion (SCC) as they possess strong spin-orbit coupling (SOC), reduced dimensionality and crystal symmetries as well as tuneable band structure, compared to metallic structures. Moreover, SCC can be tuned with the number of layers, electric field, or strain. Here, SCC in epitaxially grown 2D PtSe2 by THz spintronic emission is studied since its 1T crystal symmetry and strong SOC favor SCC. High quality of as-grown PtSe2 layers is demonstrated, followed by in situ ferromagnet deposition by sputtering that leaves the PtSe2 unaffected, resulting in well-defined clean interfaces as evidenced with extensive characterization. Through this atomic growth control and using THz spintronic emission, the unique thickness-dependent electronic structure of PtSe2 allows the control of SCC. Indeed, the transition from the inverse Rashba-Edelstein effect (IREE) in 1-3 monolayers (ML) to the inverse spin Hall effect (ISHE) in multilayers (>3 ML) of PtSe2 enabling the extraction of the perpendicular spin diffusion length and relative strength of IREE and ISHE is demonstrated. This band structure flexibility makes PtSe2 an ideal candidate to explore the underlying mechanisms and engineering of the SCC as well as for the development of tuneable THz spintronic emitters.

Giant Atomic Swirl in Graphene Bilayers with Biaxial Heterostrain.

The study of moiré engineering started with the advent of van der Waals heterostructures, in which stacking 2D layers with different lattice constants leads to a moiré pattern controlling their electronic properties. The field entered a new era when it was found that adjusting the twist between two graphene layers led to strongly-correlated-electron physics and topological effects associated with atomic relaxation. A twist is now routinely used to adjust the properties of 2D materials. This study investigates a new type of moiré superlattice in bilayer graphene when one layer is biaxially strained with respect to the other-so-called biaxial heterostrain. Scanning tunneling microscopy measurements uncover spiraling electronic states associated with a novel symmetry-breaking atomic reconstruction at small biaxial heterostrain. Atomistic calculations using experimental parameters as inputs reveal that a giant atomic swirl forms around regions of aligned stacking to reduce the mechanical energy of the bilayer. Tight-binding calculations performed on the relaxed structure show that the observed electronic states decorate spiraling domain wall solitons as required by topology. This study establishes biaxial heterostrain as an important parameter to be harnessed for the next step of moiré engineering in van der Waals multilayers.

Checkpoint Inhibitors in Combination With Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors: The CHEERS Phase 2 Randomized Clinical Trial.

Importance: Although immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and PD-1 ligand 1 have improved the outcome for many cancer types, the majority of patients fails to respond to ICI monotherapy. Hypofractionated radiotherapy has the potential to improve the therapeutic ratio of ICIs. Objective: To assess the addition of radiotherapy to ICIs compared with ICI monotherapy in patients with advanced solid tumors. Design, Setting, and Participants: This open-label, multicenter, randomized phase 2 trial was conducted in 5 Belgian hospitals and enrolled participants between March 2018 and October 2020. Patients 18 years or older with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or non-small cell lung carcinoma were eligible. A total of 99 patients were randomly assigned to either the control arm (n = 52) or the experimental arm (n = 47). Of those, 3 patients (1 in the control arm vs 2 in the experimental arm) withdrew consent and thus were not included in the analysis. Data analyses were performed between April 2022 and March 2023. Interventions: Patients were randomized (1:1) to receive anti-PD-1/PD-1 ligand 1 ICIs alone as per standard of care (control arm) or combined with stereotactic body radiotherapy 3 × 8 gray to a maximum of 3 lesions prior to the second or third ICI cycle, depending on the frequency of administration (experimental arm). Randomization was stratified according to tumor histologic findings and disease burden (3 and fewer or more than 3 cancer lesions). Main Outcomes and Measures: The primary end point was progression-free survival (PFS) as per immune Response Evaluation Criteria in Solid Tumors. Key secondary end points included overall survival (OS), objective response rate, local control rate, and toxic effects. Efficacy was assessed in the intention-to-treat population, while safety was evaluated in the as-treated population. Results: Among 96 patients included in the analysis (mean age, 66 years; 76 [79%] female), 72 (75%) had more than 3 tumor lesions and 65 (68%) had received at least 1 previous line of systemic treatment at time of inclusion. Seven patients allocated to the experimental arm did not complete the study-prescribed radiotherapy course due to early disease progression (n = 5) or intercurrent illness (n = 2). With a median (range) follow-up of 12.5 (0.7-46.2) months, median PFS was 2.8 months in the control arm compared with 4.4 months in the experimental arm (hazard ratio, 0.95; 95% CI, 0.58-1.53; P = .82). Between the control and experimental arms, no improvement in median OS was observed (11.0 vs 14.3 months; hazard ratio, 0.82; 95% CI, 0.48-1.41; P = .47), and objective response rate was not statistically significantly different (22% vs 27%; P = .56), despite a local control rate of 75% in irradiated patients. Acute treatment-related toxic effects of any grade and grade 3 or higher occurred in 79% and 18% of patients in the control arm vs 78% and 18% in the experimental arm, respectively. No grade 5 adverse events occurred. Conclusions and Relevance: This phase 2 randomized clinical trial demonstrated that while safe, adding subablative stereotactic radiotherapy of a limited number of metastatic lesions to ICI monotherapy failed to show improvement in PFS or OS. Trial Registration: ClinicalTrials.gov Identifier: NCT03511391.

Use of visual aids in general practice consultations: A questionnaire-based survey.

Objectives: Visual aids (VAs) seem effective to improve doctor-patient communication. The objective was to describe how VAs are used in consultation and what French general practitioners (GPs) expect of them. Methods: Cross-sectional study using a self-administered questionnaire among French GPs in 2019. Descriptive and multinominal logistic regression analyses were performed. Results: Of the 376 respondents, 70% used VAs at least weekly and 34% daily; 94% considered VAs useful/very useful; 77% felt they did not use VAs enough. Sketches were the most used VAs and considered the most useful. Younger age was significantly associated with a higher rate of use of simple digital images. VAs were mainly used to describe anatomy and facilitate patient comprehension. Main reasons for not using VAs more often were time spent searching, lack of habit and poor quality of available VAs. Many GPs requested a database of good quality VAs. Conclusions: GPs use VAs regularly in consultations but would like to use them more often. Informing GPs of the usefulness of VAs, training them to draw adapted sketches and creating a good quality databank are some possible strategies to increase the use of VAs. Innovation: This study described in detail the use of VAs as tool for doctor-patient communication.

Initial characteristics and course of disease in patients with suspected COVID-19 managed in general practice: a prospective, multicentre cohort study.

OBJECTIVES: To describe and compare the initial clinical characteristics of a cohort of patients with suspected COVID-19 managed by general practitioners (GPs); to assess whether 3-month persistent symptoms were more frequent among confirmed cases than among no-COVID cases; and to identify factors predictive of persistent symptoms and adverse outcomes among confirmed cases. DESIGN AND SETTING: A comparative, prospective, multicentre cohort study in primary care in the Paris region of France. PARTICIPANTS: 521 patients aged ≥18 with suspected COVID-19 were enrolled between March and May 2020. OUTCOME MEASURES: Initial symptoms, COVID-19 status, persistent symptoms 3 months after inclusion and a composite criterion for potentially COVID-19-related events (hospitalisation, death, emergency department visits). The final COVID-19 status ('confirmed', 'no-COVID' and 'uncertain' cases) was determined by the GP after the receipt of the laboratory test results. RESULTS: 516 patients were analysed; 166 (32.2%) were classified into the 'confirmed COVID' group, 180 (34.9%) into the 'no-COVID' group and 170 (32.9%) in the 'uncertain COVID' group. Confirmed cases were more likely to have persistent symptoms than no-COVID cases (p=0.09); initial fever/feeling feverish and anosmia were independently associated with persistent symptoms. At 3 months, we observed 16 (9.8%) COVID-19-related hospital admissions, 3 (1.8%) intensive care unit admissions, 13 (37.1%) referrals to an emergency department and no death. Age >70 and/or at least one comorbidity (OR 6.53; 95% CI 1.13-37.84; p=0.036), abnormalities in a lung examination (15.39; 95% CI 1.61-146.77; p=0.057) and two or more systemic symptoms (38.61; 95% CI 2.30-647.40; p=0.011) were associated with the composite criterion. CONCLUSIONS: Although most patients with COVID-19 in primary care had mild disease with a benign course, almost one in six had persistent symptoms at 3 months. These symptoms were more frequent in the 'confirmed COVID' group. Our findings need to be confirmed in a prospective study with longer follow-up.

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1.

BACKGROUND: Talazoparib has shown antitumor activity with a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC) and DNA damage response (DDR)/homologous recombination repair (HRR) alterations. OBJECTIVE: To evaluate patient-reported health-related quality of life (HRQoL) and pain in patients who received talazoparib in the TALAPRO-1 study, with a special interest in patients harboring breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. DESIGN, SETTING, AND PARTICIPANTS: TALAPRO-1 is a single-arm, phase 2 study in men with mCRPC DDR alterations either directly or indirectly involved in HRR, who previously received one to two taxane-based chemotherapy regimens for advanced prostate cancer and whose mCRPC progressed on one or more novel hormonal agents. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Men completed the European Quality-of-life Five-dimension Five-level scale (EQ-5D-5L), EQ-5D visual analog scale (VAS), and Brief Pain Inventory-Short Form at predefined time points during the study. The patient-reported outcome (PRO) population included men who completed a baseline and one or more postbaseline assessments before study end. Longitudinal mixed-effect models assuming an unstructured covariance matrix were used to estimate the mean (95% confidence interval [CI]) change from baseline for pain and general health status measurements among all patients and patients with BRCA1/2 mutations. RESULTS AND LIMITATIONS: In the 97 men in the PRO population treated with talazoparib (BRCA1/2, n = 56), the mean (95% CI) EQ-5D-5L Index improved (all patients, 0.05 [0.01, 0.08]; BRCA1/2 subset, 0.07 [0.03, 0.10]), as did the EQ-5D VAS scores (all patients, 5.42 [2.65, 8.18]; BRCA1/2 subset, 4.74 [1.07, 8.41]). Improvements in the estimated overall change from baseline (95% CI) in the mean worst pain were observed in all patients (-1.08 [-1.52, -0.65]) and the BRCA1/2 subset (-1.15 [-1.67, -0.62]). The probability of not having had experienced deterioration of worst pain by month 12 was 84% for all patients and 83% for the BRCA1/2 subset. CONCLUSIONS: In heavily pretreated men with mCRPC and DDR/HRR alterations, talazoparib was associated with improved HRQoL in all patients and the BRCA1/2 subset. In both patient groups, worst pain improved from baseline and the probability of not experiencing a deterioration in worst pain with talazoparib was high. PATIENT SUMMARY: We show that talazoparib was associated at least with no change or improvements in health-related quality of life (HRQoL) and pain burden in men with metastatic castration-resistant prostate cancer and DNA damage response/homologous recombination repair gene alterations in the TALAPRO-1 study. These findings in patient-reported HRQoL and pain complement the antitumor activity and tolerability profile of talazoparib.

Heterostrain Determines Flat Bands in Magic-Angle Twisted Graphene Layers.

The moiré of twisted graphene bilayers can generate flat bands in which charge carriers do not possess enough kinetic energy to escape Coulomb interactions with each other, leading to the formation of novel strongly correlated electronic states. This exceptionally rich physics relies on the precise arrangement between the layers. Here, we survey published scanning tunneling microscope measurements to prove that near the magic-angle, native heterostrain, the relative deformations between the layers, dominates twist in determining the flat bands as opposed to the common belief. This is demonstrated at full filling where electronic correlations have a weak effect and where we also show that tip-induced strain can have a strong influence. In the opposite situation of zero doping, we find that electronic correlation further renormalizes the flat bands in a way that strongly depends on experimental details.

Checkpoint inhibition in combination with an immunoboost of external beam radiotherapy in solid tumors (CHEERS): study protocol for a phase 2, open-label, randomized controlled trial.

BACKGROUND: While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors. METHODS/DESIGN: Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study's primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. DISCUSSION: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03511391 . Registered 17 April 2018.

Inappropriate direct oral anticoagulant prescriptions in patients with non-valvular atrial fibrillation: cross-sectional analysis of the French CACAO cohort study in primary care.

BACKGROUND: Direct oral anticoagulants (DOACs) account for an increasing proportion of prescriptions in patients with non-valvular atrial fibrillation (NVAF) in primary care. Inappropriate dosing of DOACs is a common problem, with under-dosing being a particular issue. However, conflicting results have been reported about the factors independently associated with inappropriate dosing. AIM: To describe inappropriate prescriptions of DOACs among patients in the CACAO French nationwide general practice cohort, and to identify the factors independently associated with inappropriate DOAC doses. DESIGN AND SETTING: Cross-sectional baseline analysis of the CACAO French national multicentre prospective cohort of adult patients in primary care receiving an oral anticoagulant who were recruited between April and October 2014. METHOD: A total of 1111 patients from the CACAO cohort who received a DOAC for NVAF were included in this study. Inappropriate prescriptions of DOACs were described (inappropriate dosage, contraindications, non-indications, interactions, and non-compliance with the precautions for use). Multivariate logistic models were used to investigate factors associated with inappropriate DOAC dosing (under-dosing and over-dosing). RESULTS: Overall, 438 patients (39.4%) received at least one inappropriate DOAC prescription. The most common inappropriate prescription was inappropriate dosage (n = 374, 33.7%), particularly under-dosing (n = 348, 31.3%). Multivariate analysis revealed that factors independently associated with under-dosing were older age, prescription of apixaban or dabigatran, and a CHA2DS2-VASc score ≥2 vs. a score = 1. Factors with over-dosing were kidney failure, a HAS-BLED score ≥3, and older age. CONCLUSION: The appropriateness of DOAC prescribing for NVAF can be improved, especially in older patients, and in patients with kidney failure, a higher risk of ischaemic stroke, and/or a higher risk of bleeding. GPs have a key role in increasing the proportion of appropriate DOAC prescriptions via informational, educational, and/or management strategies.

How GPs adapted their practices and organisations at the beginning of COVID-19 outbreak: a French national observational survey.

OBJECTIVES: To describe how general practitioners (GPs) adapted their practices to secure and maintain access to care in the epidemic phase. A secondary objective was to explore if GPs' individual characteristics and type of practice determined their adaptation. DESIGN: Observational study using an online questionnaire. Organisational changes were measured by a main question and detailed in two specific outcomes. To identify which GPs' characteristics impacted organisational changes, successive multivariate logistic modelling was performed. First, we identified the GPs' characteristics related to organisational changes with a univariate analysis. Then, we tested the adjusted associations between this variable and the following GPs' characteristics: age, gender and type of practice. SETTING: The questionnaire was administered online between 14 March and 21 March 2020. Practitioners were recruited by email using the contact lists of different French scientific GP societies. PARTICIPANTS: The target population was GPs currently practising in France (n=46 056). We obtained a total of 7481 responses. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: Proportion of GPs who adapted their practice. Secondary outcome: GPs' characteristics related to organisational changes. RESULTS: Among the 7481 responses, 5425 were complete and were analysed. 3849 GPs (70.9%) changed their activity, 3605 GPs (66.5%) increased remote consultations and 2315 GPs (42.7%) created a specific pathway for probable patients with COVID-19. Among the 3849 GPs (70.9%) who changed their practice, 3306 (91.7%) gave more answers by phone, 996 (27.6%) by email and 1105 (30.7%) increased the use of video consultations. GPs working in multi-professional group practices were more likely to have changed their activity since the beginning of the epidemic wave than GPs working in mono-professional group or single medical practices (adjusted OR: 1.32, 95% CI 1.12 to 1.56, p=0.001). CONCLUSIONS: French GPs adapted their practices regarding access to care for patients in the context of the COVID-19 epidemic. This adaptation was higher in multi-professional group practices.

Predictive factors for non-participation or partial participation in breast, cervical and colorectal cancer screening programmes†.

BACKGROUND: No study has investigated factors associated with non-participation or partial participation in the different combination patterns of screening programmes for all three cancers, that is, breast, colorectal and cervical cancer. METHODS: In a retrospective cohort study, we sought to describe combinations of cancer screening participation rates among women in the Val-de-Marne area of France and to identify individual and contextual factors associated with non-participation or partial participation. RESULTS: Women aged between 50 and 65 and who were eligible for all three screening programmes (n = 102 219) were analysed in multilevel logistic models, with the individual as the Level 1 variable and the place of residence as the Level 2 variable. The women who did not participate in any of the screening programmes were 34.4%, whereas 30.1%, 24% and 11.5% participated in one, two or all three screening programmes, respectively. Age below 55, a previous false-positive mammography, prior opportunistic mammography only, no previous mammography, membership of certain health insurance schemes (all P < 0.05) and residence in a deprived area (P < 0.001) were independently associated with non-participation or partial participation. We observed a stronger effect of deprivation on non-participation in all three cancers than in combinations of screening programmes. CONCLUSION: Our findings suggest that the health authorities should focus on improving cancer screenings in general rather than screenings for specific types of cancer, especially among younger women and those living in the most socially deprived areas.

Changes over time in attitudes towards the management of older patients with heart failure by general practitioners: a qualitative study.

BACKGROUND: Underdiagnosis and undertreatment of chronic heart failure (CHF) are common in older patients, who are usually treated by general practitioners (GPs). In 2007, the French ICAGE study explored GPs' attitudes to the management of this condition in older patients. OBJECTIVES: To explore changes over time in GPs' attitudes towards the management of CHF in patients aged ≥75 and to identify barriers to optimal management. METHODS: In 2015, we performed a qualitative study of 20 French GPs via semi-structured interviews and a thematic content analysis. The results were compared with the findings of a 2007 study. RESULTS: In 2015, the perceived barriers to diagnosis were the same as in 2007. Echocardiography was still the preferred diagnostic method but the GPs relied on the cardiologist to confirm the diagnosis. Many GPs were still unaware of the different types of CHF. In contrast, they reported greater knowledge of decompensation factors and the ultrasound criteria for CHF. They also prescribed a brain natriuretic peptide assay more frequently. Angiotensin-converting enzyme inhibitors and beta blockers were more strongly perceived to be core treatments. Few GPs initiated drug treatments and optimized dosages. Although patient education was never mentioned, the importance of multidisciplinary care was emphasized. CONCLUSION: Our results evidenced a small recent improvement in the management of older patients with CHF. Appropriate guidelines and training for GPs, patient education and multidisciplinary collaboration might further improve the care given to this population.

Weekly carboplatin plus neoadjuvant anthracycline-taxane-based regimen in early triple-negative breast cancer: a prospective phase II trial by the Breast Cancer Task Force of the Belgian Society of Medical Oncology (BSMO).

AIM: To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients. METHODS: Patients were included if they had stage II and III TNBC and received wP (80 mg/m2/week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery. RESULTS: Sixty-three eligible patients were included. Median age was 51 years (range 29-74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy. CONCLUSION: The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability.

Mandatory vaccination of infants in France: Is that the way forward?

In this opinion paper, the authors argue that the extension of mandatory immunization of infants up to two years of age from three diseases (diphtheria, tetanus, poliomyelitis) to 11 diseases, introduced in France in January 2018, is not a sustainable response to the challenge of controlling vaccine-preventable diseases. In France in 2017, infant immunization coverage (IC) rates were sufficiently high or increasing (hepatitis B), except for measles, mumps and rubella (MMR) and meningococcus C disease. Even if vaccination obligation makes it possible to achieve the MMR IC objectives among infants, communication programmes and supported advice from GPs are essential for the catch-up of susceptible adults to obtain herd immunity. The impact of mandatory immunization on hesitancy remains uncertain, and it contradicts the evolution of the patient's role in the governance of his own health and the principle of autonomy. Numerous studies have shown that interventions and advice from health professionals improve vaccine acceptance. To correct the poor implementation of some vaccination programmes by health professionals, strong communication and resources from health authorities are needed, rather than a retreat towards obligation. Reducing missed opportunities and increasing access to immunization are essential objectives. Finally, an immunization policy based on primary care and a patient-centred approach to each vaccination are more likely to reduce vaccine hesitancy, sustainably.

Electronic Spectrum of Twisted Graphene Layers under Heterostrain.

We demonstrate that stacking layered materials allows a strain engineering where each layer is strained independently, which we call heterostrain. We combine detailed structural and spectroscopic measurements with tight-binding calculations to show that small uniaxial heterostrain suppresses Dirac cones and leads to the emergence of flat bands in twisted graphene layers (TGLs). Moreover, we demonstrate that heterostrain reconstructs, much more severely, the energy spectrum of TGLs than homostrain for which both layers are strained identically, a result which should apply to virtually all van der Waals structures opening exciting possibilities for straintronics with 2D materials.

Health sciences libraries' subscriptions to journals: expectations of general practice departments and collection-based analysis.

OBJECTIVE: The aims of this study were to (i) assess the expectations of general practice departments regarding health sciences libraries' subscriptions to journals and (ii) describe the current general practice journal collections of health sciences libraries. METHODS: A cross-sectional survey was distributed electronically to the thirty-five university general practice departments in France. General practice departments were asked to list ten journals to which they expected access via the subscriptions of their health sciences libraries. A ranked reference list of journals was then developed. Access to these journals was assessed through a survey sent to all health sciences libraries in France. Adequacy ratios (access/need) were calculated for each journal. RESULTS: All general practice departments completed the survey. The total reference list included 44 journals. This list was heterogeneous in terms of indexation/impact factor, language of publication, and scope (e.g., patient care, research, or medical education). Among the first 10 journals listed, La Revue Prescrire (96.6%), La Revue du Praticien-Médecine Générale (90.9%), the British Medical Journal (85.0%), Pédagogie Médicale (70.0%), Exercer (69.7%), and the Cochrane Database of Systematic Reviews (62.5%) had the highest adequacy ratios, whereas Family Practice (4.2%), the British Journal of General Practice (16.7%), Médecine (29.4%), and the European Journal of General Practice (33.3%) had the lowest adequacy ratios. CONCLUSIONS: General practice departments have heterogeneous expectations in terms of health sciences libraries' subscriptions to journals. It is important for librarians to understand the heterogeneity of these expectations, as well as local priorities, so that journal access meets users' needs.

Efficacy of nurse-led and general practitioner-led comprehensive geriatric assessment in primary care: protocol of a pragmatic three-arm cluster randomised controlled trial (CEpiA study).

INTRODUCTION: Older patients raise therapeutic challenges, because they constitute a heterogeneous population with multimorbidity. To appraise this complexity, geriatricians have developed a multidimensional comprehensive geriatric assessment (CGA), which may be difficult to apply in primary care settings. Our primary objective was to compare the effect on morbimortality of usual care compared with two complex interventions combining educational seminars about CGA: a dedicated geriatric hotline for general practitioners (GPs) and CGA by trained nurses or GPs. METHODS AND ANALYSIS: The Clinical Epidemiology and Ageing study is an open-label, pragmatic, multicentre, three-arm, cluster randomised controlled trial comparing two intervention groups and one control group. Patients must be 70 years or older with a long-term illness or with unscheduled hospitalisation in the past 3 months (750 patients planned). This study involves volunteering GPs practising in French primary care centres, with randomisation at the practice level. The multifaceted interventions for interventional arms comprise an educational interactive multiprofessional seminar for GPs and nurses, a geriatric hotline dedicated to GPs in case of difficulties and the performance of a CGA updated to primary care. The CGA is systematically performed by a nurse in arm 1 but is GP-led on a case-by-case basis in arm 2. The primary endpoint is a composite criterion comprising overall death, unscheduled hospitalisations, emergency admissions and institutionalisation within 12 months after inclusion. Intention-to-treat analysis will be performed using mixed-effects logistic regression models, with adjustment for potential confounders. ETHICS AND DISSEMINATION: The protocol was approved by an appropriate ethics committee (CPP Ile-de-France IV, Paris, France, approval April 2015;15 664). This study is conducted according to principles of good clinical practice in the context of current care and will provide useful knowledge on the clinical benefits achievable by CGA in primary care. TRIAL REGISTRATION NUMBER: NCT02664454; Pre-results.

Graphene as a Mechanically Active, Deformable Two-Dimensional Surfactant.

In crystal growth, surfactants are additive molecules used in dilute amount or as dense, permeable layers to control surface morphologies. We investigate the properties of a strikingly different surfactant: a 2D and covalent layer with close atomic packing, graphene. Using in situ, real-time electron microscopy, scanning tunneling microscopy, kinetic Monte Carlo simulations, and continuum mechanics calculations, we reveal why metallic atomic layers can grow in a 2D manner below an impermeable graphene membrane. Upon metal growth, graphene dynamically opens nanochannels called wrinkles, facilitating mass transport while at the same time storing and releasing elastic energy via lattice distortions. Graphene thus behaves as a mechanically active, deformable surfactant. The wrinkle-driven mass transport of the metallic layer intercalated between graphene and the substrate is observed for two graphene-based systems, characterized by different physicochemical interactions, between graphene and the substrate and between the intercalated material and graphene. The deformable surfactant character of graphene that we unveil should then apply to a broad variety of species, opening new avenues for using graphene as a 2D surfactant forcing the growth of flat films, nanostructures, and unconventional crystalline phases.