Paramagnetic Singularities of the Orbital Magnetism in Graphene with a Moiré Potential.

The recent detection of the singular diamagnetism of Dirac electrons in a single graphene layer paved a new way of probing 2D quantum materials through the measurement of equilibrium orbital currents which cannot be accessed in usual transport experiments. Among the theoretical predictions is an intriguing orbital paramagnetism at saddle points of the dispersion relation. Here we present magnetization measurements in graphene monolayers aligned on hexagonal boron nitride crystals. Besides the sharp diamagnetic McClure response at the Dirac point, we detect extra diamagnetic singularities at the satellite Dirac points of the moiré lattice. Surrounding these diamagnetic satellite peaks, we also observe paramagnetic peaks located at the chemical potential of the saddle points of the graphene moiré band structure and relate them to the presence of van Hove logarithmic singularities in the density of states. These findings reveal the long ago predicted anomalous paramagnetic orbital response in 2D systems when the Fermi energy is tuned to the vicinity of saddle points.

Detection of graphene's divergent orbital diamagnetism at the Dirac point.

The electronic properties of graphene have been intensively investigated over the past decade. However, the singular orbital magnetism of undoped graphene, a fundamental signature of the characteristic Berry phase of graphene's electronic wave functions, has been challenging to measure in a single flake. Using a highly sensitive giant magnetoresistance (GMR) sensor, we have measured the gate voltage­dependent magnetization of a single graphene monolayer encapsulated between boron nitride crystals. The signal exhibits a diamagnetic peak at the Dirac point whose magnetic field and temperature dependences agree with long-standing theoretical predictions. Our measurements offer a means to monitor Berry phase singularities and explore correlated states generated by the combined effects of Coulomb interactions, strain, or moiré potentials.

Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

Very low field magnetic resonance imaging with spintronic sensors.

A very low field magnetic resonance imaging (MRI) setup based on magnetoresistive-superconducting mixed sensors is presented. A flux transformer is used to achieve coupling between the sample to image and the mixed sensor. The novel detector was implemented in a spin echo MRI experiment, exposing the mixed sensor to RF pulses without use of any RF switch. The performance of the novel detector is given in terms of signal-to-noise ratio and is compared with classical tuned coils.

Spintronic platforms for biomedical applications.

Since the fundamental discovery of the giant magnetoresistance many spintronic devices have been developed and implemented in our daily life (e.g. information storage and automotive industry). Lately, advances in the sensors technology (higher sensitivity, smaller size) have potentiated other applications, namely in the biological area, leading to the emergence of novel biomedical platforms. In particular the investigation of spintronics and its application to the development of magnetoresistive (MR) biomolecular and biomedical platforms are giving rise to a new class of biomedical diagnostic devices, suitable for bench top bioassays as well as point-of-care and point-of-use devices. Herein, integrated spintronic biochip platforms for diagnostic and cytometric applications, hybrid systems incorporating magnetoresistive sensors applied to neuroelectronic studies and biomedical imaging, namely magneto-encephalography and magneto-cardiography, are reviewed. Also lab-on-a-chip MR-based platforms to perform biological studies at the single molecule level are discussed. Overall the potential and main characteristics of such MR-based biomedical devices, comparing to the existing technologies while giving particular examples of targeted applications, are addressed.

Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial.

AIMS: To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. METHODS: In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with Type 1 diabetes (40 women) currently treated with multiple daily injections, age 18-65 years and HbA(1c) ≥ 8.2% (≥ 66 mmol/mol) to 26 weeks of treatment with either a sensor-augmented insulin pump (n = 44) (Paradigm(®) REAL-Time) or continued with multiple daily injections (n = 39). Change in HbA(1c) between baseline and 26 weeks, sensor-derived endpoints and patient-reported outcomes were assessed. RESULTS: The trial was completed by 43/44 (98%) patients in the sensor-augmented insulin pump group and 35/39 (90%) patients in the multiple daily injections group. Mean HbA(1c) at baseline and at 26 weeks changed from 8.46% (SD 0.95) (69 mmol/mol) to 7.23% (SD 0.65) (56 mmol/mol) in the sensor-augmented insulin pump group and from 8.59% (SD 0.82) (70 mmol/mol) to 8.46% (SD 1.04) (69 mmol/mol) in the multiple daily injections group. Mean difference in change in HbA(1c) after 26 weeks was -1.21% (95% confidence interval -1.52 to -0.90, P < 0.001) in favour of the sensor-augmented insulin pump group. This was achieved without an increase in percentage of time spent in hypoglycaemia: between-group difference 0.0% (95% confidence interval -1.6 to 1.7, P = 0.96). There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group (P = 0.21). Problem Areas in Diabetes and Diabetes Treatment Satisfaction Questionnaire scores improved in the sensor-augmented insulin pump group. CONCLUSIONS: Sensor augmented pump therapy effectively lowers HbA(1c) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections.

Flux transformers made of commercial high critical temperature superconducting wires.

We have designed flux transformers made of commercial BiSCCO tapes closed by soldering with normal metal. The magnetic field transfer function of the flux transformer was calculated as a function of the resistance of the soldered contacts. The performances of different kinds of wires were investigated for signal delocalization and gradiometry. We also estimated the noise introduced by the resistance and showed that the flux transformer can be used efficiently for weak magnetic field detection down to 1 Hz.

Fertility and obstetrical complications in women with LMNA-related familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy due to LMNA (lamin A/C) mutations is a rare disorder characterized by a selective loss of adipose tissue and insulin resistance. Dyslipidemia and severe diabetes often occur during its evolution. Only isolated and contradictory case reports have been published on the obstetrical prognosis in lipodystrophy. The aim of our study was to compare the fertility and occurrence of obstetrical complications of women with familial partial lipodystrophy due to LMNA (lamin A/C) mutations with those of nonaffected relatives, women from the general population, and women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: Data were obtained from clinical follow-up of seven families with patients exhibiting mutations in LMNA (five R482W, one R482Q, one R439C) (14 affected among 48 women). RESULTS: The mean number of live children per woman was 1.7 in affected patients vs. 2.8 in nonaffected relatives. Fifty-four percent of LMNA-mutated women exhibited a clinical phenotype of PCOS, 28% suffered from infertility, 50% experienced at least one miscarriage, 36% developed gestational diabetes, and 14% experienced eclampsia and fetal death. Mean blood leptin level was significantly lower in LMNA-mutated patients than in nonaffected relatives (5.0 +/- 3.8 ng/ml vs 14.3 +/- 3.6; P < 0.001) despite similar body mass index (21.0 +/- 4.2 vs 22.4 +/- 2.2; P = 0.49). CONCLUSION: In these LMNA-linked lipodystrophic patients, the prevalence of PCOS, infertility, and gestational diabetes was higher than in the general population. Moreover, the prevalence of gestational diabetes and miscarriages was higher in lipodystrophic LMNA-mutated women than previously reported in PCOS women with similar body mass index. Women with lipodystrophies due to LMNA mutations are at high risk of infertility, gestational diabetes, and obstetrical complications and require reinforced gynecological and obstetrical care.

Familial partial lipodystrophy due to the LMNA R482W mutation with multinodular goitre, extrapyramidal syndrome and primary hyperaldosteronism.

Objective To describe new data about the wide phenotypic variability of diseases due to mutations in the lamin A/C gene (LMNA). Design We report a complex phenotype in a patient with familial partial lipodystrophy of the Dunnigan type (FPLD) and study the frequency of her unusual clinical signs in 19 other LMNA-mutated lipodystrophic patients from 8 different families and 14 non-mutated family members. Case Report The patient was diagnosed with FPLD due to the R482W LMNA mutation after familial screening. Surprisingly, she had no biological signs of insulin resistance. The presence of hypertension with hypokalaemia led to the diagnosis of primary hyperaldosteronism. Thyroid investigations showed a euthyroid multinodular goiter. In addition, the patient exhibited a juvenile akineto-hypertonic syndrome. Results Goiter was identified with a similar frequency (55%) in LMNA-mutated lipodystrophic patients (11 out of 20, originating from 5 families among 8) compared to non-mutated family controls (35%; 5 patients out of 14, all originating from the same family). No case of primary hyperaldosteronism or extrapyramidal syndrome was identified in other studied subjects, either LMNA-mutated or not. Conclusions This R482W-LMNA mutated patient showed an association of features (primary hyperaldosteronism, euthyroid goiter and extra-pyramidal syndrome, raising the question of a link with her laminopathy. Prevalence of goiter tended to be higher in LMNA-mutated than in non-mutated subjects. Hyperaldosteronism seems coincidental. Although extrapyramidal syndrome has never been reported in lipodystrophic patients, it may nevertheless be linked to the LMNA mutation since multiple neurological features have been associated with alterations in lamins A/C.

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

Subcutaneous insulin resistance successfully circumvented on long term by peritoneal insulin delivery from an implantable pump in four diabetic patients.

UNLABELLED: Extreme subcutaneous insulin resistance is a rare syndrome characterized by a severe resistance to subcutaneous (S/C) insulin together with persistence of normal or near normal intravenous (IV) insulin sensitivity. Its pathophysiology is unknown, although increased insulin degrading activity has been reported in the S/C adipose tissue fraction in some cases. Until now, proposed treatments have been disappointing. We report 4 cases who were successfully treated by intraperitoneal (IP) route. METHODS: The diagnosis of subcutaneous insulin resistance was based upon following combined conditions: resistance to hypoglycaemic action of subcutaneous insulin but normal or near normal sensitivity to IV or IP insulin. RESULTS: 4 patients among those followed by EVADIAC group met these criteria: 3 with type 1 diabetes (C peptide=0), the last one with unexplained non insulin-deficient diabetes (no anti-GAD antibodies, C peptide=5 ng/ml). All of them had been treated with subcutaneous insulin therapy without success despite huge doses (up to 4000 IU/day in two patients). The 3 type 1 diabetic patients presented with a history of repeated ketoacidosis episodes. A treatment of insulin mixed with aprotinin had been proposed to 2 patients without success. The IV insulin sensitivity was proved to be normal in two patients by euglycaemic clamp data. A skin biopsy was performed in 1 patient. An accumulation of insulin in the derma was revealed with no increase of degradation products of insulin. In these 4 patients, a dramatic improvement of diabetes control was obtained by IP insulin delivery from an implantable pump (HbA1c decrease by at least 3%). CONCLUSION: Although pathophysiology of the subcutaneous insulin resistance syndrome remains unexplained, our data show that intra-peritoneal insulin therapy from an implantable pump allows diabetes control in patients affected by this uncommon but severely disabling condition.

Advantages to using capillary blood beta-hydroxybutyrate determination for the detection and treatment of diabetic ketosis.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

Extreme subcutaneous insulin resistance: a misunderstood syndrome.

Extreme subcutaneous insulin resistance (SIR) is a rare syndrome characterized by severe resistance to subcutaneous insulin with normal intravenous insulin sensitivity. Its pathophysiology is unknown, though an increased insulin degrading activity has been suggested. We report the case of a 35 year-old female patient with type I diabetes since the age of 3. Despite five shots of insulin/day, the patient progressively developed permanent ketosis related to severe acquired SIR with insulin doses as high as 500 U/day. Subcutaneous infusion of insulin and lispro insulin through an external pump did not improve resistance: HbA(1c) levels remained between 14 and 18% (N<6.5%). After numerous ketoacidotic episodes, continuous ambulatory intravenous insulin infusion was attempted through a central port due to a lack of peripheral venous access. HbAlc improved (8.5%) and daily insulin needs decreased to below 40U. However, the treatment had to be discontinued because of thrombosis and infection at different times. Intraperitoneal insulin infusion with an external pump was then proposed. HbAlc improved to 8% during 18 months but several episodes of catheter infection and encapsulation led to its removal. An intraperitoneal pump was surgically implanted, leading to the stabilization of HbA(1c) to around 8%. An insulin degradation assay did not demonstrate any excess of insulin degrading activity in the patient's or controls' subcutaneous tissue; nevertheless, excessive amounts of insulin were found in the patient's derm compared to controls. This case report of acquired SIR raises the question of its treatment and mechanisms. Regarding treatment, intraperitoneal delivery of insulin appears to be the best solution, but the mechanisms underlying SIR still remain unclear.

[Today data management in self-monitoring of blood glucose for diabetic patients]. / Data management aujourd'hui dans l'autosurveillance des patients diabétiques.

Improving diabetes treatment needs intensive glucose monitoring which is restricting for patients and time-consuming for physicians. Up-to-date tools of data management were developed, following progress in computing technology and home computing. Glucometers with memory and softwares are able to improve data management of self blood glucose monitoring, personalized interactivity with physician. They are very important to develop telemedecine systems in diabetes care. These systems are designed to complement the daily care and intensive management of diabetics through telemonitoring and telecare services.

Individual domain wall resistance in submicron ferromagnetic structures.

The resistance generated by individual domain walls is measured in a FePd nanostructure. Combining transport and magnetic imaging measurements, the intrinsic domain wall resistance is quantified. It is found positive and of a magnitude consistent with that predicted by models based on spin scattering effects within the walls. This magnetoresistance at a nanometer scale allows a direct counting of the number of walls inside the nanostructure. The effect is then used to measure changes in the magnetic configuration of submicron stripes under application of a magnetic field.

Spin wave wells in nonellipsoidal micrometer size magnetic elements.

We show experimentally and by model calculations that in finite, nonellipsoidal, micrometer size magnetic thin film elements the dynamic magnetic eigenexcitations (spin waves) may exhibit strong spatial localization. This localization is due to the formation of a potential well for spin waves in the highly inhomogeneous internal magnetic field within the element.

Chest radiograph interpretation skills of anesthesiologists.

OBJECTIVE: To assess the skills of anesthesiologists in the interpretation of chest radiographs. DESIGN: Randomized evaluation conducted among anesthesiologists and radiologists. SETTING: Postgraduate Assembly of the New York State Society of Anesthesiologists in 1999, and the Department of Radiology, New York University Medical Center. PARTICIPANTS: A total of 61 anesthesiologists (48 attending physicians; 13 residents); control group of 8 radiology residents (all participants volunteered). INTERVENTIONS: After completing a demographic survey, participants were asked to review a series of 10 chest radiographs. A brief clinical scenario accompanied each radiograph. No time limit was set for these interpretations. MEASUREMENTS AND MAIN RESULTS: The demographic characteristics of the anesthesiology participants included university faculty (46%), private group practitioners (41%), independent practitioners (11%), and 1 participant with an unspecified type of practice. Additional training among the participants included internal medicine (31%), surgery (19%), and pediatrics (3%); 34% did not specify any additional training. Of the participants, 92% were involved in cases requiring general anesthesia; 96% managed patients in the recovery room; and 34% managed patients in the intensive care unit. Of participants, 80% usually order chest radiographs, but only 42% interpret the films themselves. Misdiagnosed radiographs included pneumothorax by 11% of participants, free air under the diaphragm by 41%, bronchial perforation from a nasogastric tube by 28%, right mainstem intubation by 20%, superior vena cava perforation from a central venous catheter by 31%, normal film by 75%, negative pressure pulmonary edema by 16%, left lower lobe collapse by 80%, pulmonary infarction from a pulmonary artery catheter by 29%, and tension pneumothorax by 41%. Overall scores of the attending physicians were not significantly different from that of residents (p > 0.05). The control group of radiology residents scored significantly better (mean, 83.7; p = 0.009) than the anesthesia residents (mean, 62.8) and anesthesia attending physicians (mean, 62.5). CONCLUSION: Anesthesiologists are deficient in skills for the interpretation of chest radiographs. The skill level of university-based physicians is not greater than physicians in private practice, and skill level does not improve with level of training or experience. Most anesthesiologists rely on radiologists for interpretative results. Further training during the residency years may help improve diagnostic skills.

Factor VII, tissue factor pathway inhibitor, and monocyte tissue factor in diabetes mellitus: influence of type of diabetes, obesity index, and age.

Changes of the tissue factor (TF) pathway of blood coagulation have been described in diabetes and could be involved in its vascular complications. In order to evaluate the influence of the type of diabetes and of the obesity index and age on these changes, factor VII coagulant activity, factor VII antigen, activated factor VII, monocyte TF expression, and plasma Tissue Factor Pathway Inhibitor (TFPI) were examined in 18 Type 1 and 16 Type 2 diabetic patients compared to non-diabetic control subjects matched for age, sex, and obesity index (Types 1 and 2 controls, respectively). Multicomplicated patients were excluded. FVIIc, FVIIAg, and FVIIa were higher in Type 2 diabetic patients and controls than in Type 1 diabetic patients and controls (P< .03). However, FVIIc and FVIIAg were lower in diabetic patients than in their matched controls (P< .03). Monocyte expression of TF was not different between Types 1 and 2 diabetic patients and their matched controls except for LPS-stimulated monocyte TF activity which was lower in Type 2 diabetic patients than in Type 2 controls (P< .05). Plasma TFPI was slightly but significantly higher in Type 1 diabetic patients than in Type 1 controls (P= .01) and was correlated to glycemia. However, both in Type 2 diabetic patients and controls, TFPI was higher than in Type 1 controls and was correlated with BMI (P< .0003). These results indicate that in not multicomplicated patients, the increase of FVII and TFPI was highly dependent on obesity index and age rather than on diabetes by itself.

Anisotropy of domain wall resistance

The resistive effect of domain walls in FePd films with perpendicular anisotropy was studied experimentally as a function of field and temperature. The films were grown directly on MgO substrates, which induces an unusual virgin magnetic configuration composed of 60 nm wide parallel stripe domains. This allowed us to carry out the first measurements of the anisotropy of domain wall resistivity in the two configurations of current perpendicular and parallel to the walls. At 18 K, we find 8.2% and 1.3% for the domain wall magnetoresistance normalized to the wall width (8 nm) in these two respective configurations. These values are consistent with the predictions of Levy and Zhang.