Pronounced polarization-induced energy level shifts at boundaries of organic semiconductor nanostructures.

Organic semiconductor devices rely on the movement of charge at and near interfaces, making an understanding of energy level alignment at these boundaries an essential element of optimizing materials for electronic and optoelectronic applications. Here we employ low temperature scanning tunneling microscopy and spectroscopy to investigate a model system: two-dimensional nanostructures of the prototypical organic semiconductor, PTCDA (3,4,9,10-perylenetetracarboxylic dianhydride) adsorbed on NaCl (2 ML)/Ag(111). Pixel-by-pixel scanning tunneling spectroscopy allows mapping of occupied and unoccupied electronic states across these nanoislands with sub-molecular spatial resolution, revealing strong electronic differences between molecules at the edges and those in the centre, with energy level shifts of up to 400 meV. We attribute this to the change in electrostatic environment at the boundaries of clusters, namely via polarization of neighbouring molecules. The observation of these strong shifts illustrates a crucial issue: interfacial energy level alignment can differ substantially from the bulk electronic structure in organic materials.

Collinear generation of ultrashort UV and XUV pulses.

We demonstrate the collinear generation of few-femtosecond ultraviolet and attosecond extreme ultraviolet pulses via a combination of third-harmonic and high harmonic generation in noble gases. The ultrashort coherent light bursts are produced by focusing a sub-1.5-cycle near-infrared/visible laser pulse in two subsequent quasi-static noble gas targets. This approach provides an inherently synchronized pair of UV and XUV pulses, where the UV radiation has a photon energy of approximately 5 eV and a pulse energy of up to 1 microJ and the XUV radiation contains up to 3.5 10(6) XUV photons per shot with a photon energy exceeding 100 eV. This source represents a novel tool for future UV pump/XUV probe experiments with unprecedented time-resolution.

Temperature dependence of conformation, chemical state, and metal-directed assembly of tetrapyridyl-porphyrin on Cu(111).

We present a combined scanning tunneling microscopy (STM), near-edge x-ray-absorption fine-structure, and x-ray photoemission spectroscopy (XPS) study on the bonding and ordering of tetrapyridyl-porphyrin molecules on the Cu(111) surface in the 300-500 K temperature range. Following deposition at 300 K the molecules are adsorbed with a pronounced conformational adaptation of the anchored species featuring a saddle-shaped macrocycle and terminal groups pointing toward the substrate. Upon moderate annealing supramolecular chains evolve that are stabilized by metal-ligand interactions between the mesopyridyl substituents and copper adatoms resulting in twofold copper coordination. Annealing to temperatures exceeding 450 K strongly alters the molecular appearance in high-resolution STM data. This modification was also induced by controlled voltage pulses and related to a deprotonation of the molecule by XPS. Under appropriate conditions a novel binding motif leads to honeycomb structures coexisting with the chain segments. The conformation withstands annealing without large modification.

Dimerization boosts one-dimensional mobility of conformationally adapted porphyrins on a hexagonal surface atomic lattice.

We employed temperature-controlled fast-scanning tunneling microscopy to monitor the diffusion of tetrapyridylporphyrin molecules on the Cu(111) surface. The data reveal unidirectional thermal migration of conformationally adapted monomers in the 300-360 K temperature range. Surprisingly equally oriented molecules spontaneously form dimers that feature a drastically increased one-dimensional diffusivity. The analysis of the bonding and mobility characteristics indicates that this boost is driven by a collective transport mechanism of a metallosupramolecular complex.

Self-assembly and conformation of tetrapyridyl-porphyrin molecules on Ag(111).

We present a low-temperature scanning tunneling microscopy (STM) study on the supramolecular ordering of tetrapyridyl-porphyrin (TPyP) molecules on Ag(111). Vapor deposition in a wide substrate temperature range reveals that TPyP molecules easily diffuse and self-assemble into large, highly ordered chiral domains. We identify two mirror-symmetric unit cells, each containing two differently oriented molecules. From an analysis of the respective arrangement it is concluded that lateral intermolecular interactions control the packing of the layer, while its orientation is induced by the coupling to the substrate. This finding is corroborated by molecular mechanics calculations. High-resolution STM images recorded at 15 K allow a direct identification of intramolecular features. This makes it possible to determine the molecular conformation of TPyP on Ag(111). The pyridyl groups are alternately rotated out of the porphyrin plane by an angle of 60 degrees.

Sulfate production depicts fed-state adaptation to protein restriction in humans.

One feature of the adaptation to dietary protein restriction is reduced urea production over the hours after consumption of a test meal of fixed composition. This adaptation is impaired in conventionally treated insulin-dependent diabetes mellitus (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol Endocrinol Metab 272: E59--E67, 1997). We have now tested the response to a test meal containing less protein and included as a main outcome variable the production of sulfate, a specific indicator of sulfur amino acid catabolism. Six normal men consumed a mixed test meal containing 0.25 g protein/kg and 10 kcal/kg while adapted to high (1.5 g x kg(-1) x day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes. They followed the identical protocol twice. Six subjects with insulin-dependent diabetes consumed the test meal while adapted to their customary high-protein diet. Adaptation to protein restriction reproducibly reduced 9-h cumulative postmeal urea N and S production by 22--29% and 49--52%, respectively (both P < 0.05). Similar results were obtained for a postmeal collection period of 6 h. The response of the diabetic subjects was normal. We conclude that reductions in postmeal urea and sulfate production after protein restriction are reproducible and are evident using a postmeal collection period as short as 6 h. Sulfate production effectively depicts fed-state adaptation to protein restriction.

Psychosocial issues in pediatric diabetes.

Although the majority of diabetic patients exhibit mild depression, anxiety, and somatic complaints at the time of diagnosis, these symptoms are usually temporary and resolve within 6 to 9 months. However, in some patients, depressive symptoms may increase with the duration of diabetes. Anxiety seems to increase and to be more prevalent in girls than in boys. Depression and self-esteem problems have a negative impact on the adaptation to diabetes and metabolic control. Patients' adjustment to diabetes shortly after diagnosis seems to predict adjustment later on. Family characteristics have major implications in the patient's adjustment to diabetes, self-management, and quality of life. Children and adolescents living in families with a high degree of conflict or that are less caring appear to have poorer metabolic control. Thus, the goal of achieving metabolic and psychological stability requires a diabetes team equipped to provide social and psychological support in addition to the development of technical skills. This includes very early assessment of family dynamics and psychological intervention.

Home-based management can achieve intensification cost-effectively in type I diabetes.

BACKGROUND: Newly diagnosed insulin-dependent diabetic children are most often admitted to hospital for education and insulin management and subsequently followed in outpatient clinics or office settings. However, most could be managed at home, given adequate family and health care team support and subsequent follow-up facilitated by home-based nursing intervention. We conducted a randomized trial of clinical, psychosocial, and cost effects of home-based management in a 2-year follow-up study of newly diagnosed diabetic children. METHODS: Sixty three patients were randomly assigned to traditional hospitalization and outpatient follow-up (hospital-based group) or home management (home-based group). Treatment differences between the two groups consisted of duration of initial hospital stay, site and timing of initial teaching, and nature and extent of subsequent nursing follow-up. Metabolic control was assessed by means of quarterly glycosylated hemoglobin measurements for 24 months and then at 36 months. Diabetes-related adverse events, knowledge of diabetes, adherence to the diabetes regimen, psychosocial impact, and social (total) costs incurred were assessed for 24 months. FINDINGS: Glycosylated hemoglobin concentrations were significantly lower in the home-based group at 12 to 24 months and at 36 months. Both groups had comparable numbers of diabetes-related adverse events. There were no significant group differences in psychosocial impact. Parents in the home-based group spent significantly fewer hours on diabetes care and incurred significantly lower out-of-pocket expenses during the 1st month. Health care sector costs were significantly higher. Hospital costs were $889 higher, and government costs $890 higher per child. Social (total) costs were only $48 higher per case (NS) with home care when parents' time was valued at $11.88 per hour. INTERPRETATION: Home-based management for newly diagnosed diabetic children can result in better metabolic control and similar psychosocial outcomes compared with traditional hospital- and clinic-based care without notable effects on social (total) costs.

An economic evaluation of home care for children with newly diagnosed diabetes: results from a randomized controlled trial.

OBJECTIVE: This study was undertaken to determine the health and cost effects of using home care to treat newly diagnosed Type I diabetic children rather than traditional inpatient hospital care. There had been no well-designed evaluations of home care for such children, and very few for children with other health conditions. METHODS: Sixty-three children seen at the Montreal Children's Hospital were randomly assigned at diagnosis to home care or traditional inpatient care. The children in the former group were discharged once their metabolic condition stabilized; insulin adjustments and teaching were done in their homes by a trained nurse. The children in the latter group remained hospitalized for insulin adjustments and teaching. All were followed for 24 months. The cost effects were estimated using hospital and parental data. RESULTS: Social costs were only $48 higher with home care. It had little effect on social costs, because the increased costs of health care services with home care ($768) were largely offset by parental cost savings ($720). Home care improved the children's metabolic outcomes without adversely affecting their psychosocial outcomes. CONCLUSIONS: Using home care to reduce hospital stays for children with newly diagnosed Type I diabetes improved the children's health outcomes without significantly increasing social costs.

Metabolic adaptation to protein restriction in insulin-dependent diabetes mellitus.

Eight normal subjects, four subjects with intensively treated insulin-dependent diabetes mellitus (IDDM), and six subjects with conventionally treated IDDM consumed a test meal of 0.5 g protein and 10 kcal per kg body weight, first while adapted to a conventional diet high in protein, and then again after 5 days of dietary protein restriction. Metabolic N balance (N consumed minus urea production) and net protein utilization were measured over the 9 h after consumption of the test meal, as was recovery in urea of 15N from a tracer dose of [15N]alanine included in each test meal. After the first test meal, N balance and net protein utilization were similar and close to zero for all groups. After the second test meal, N balance and net protein utilization became positive for all groups (P < 0.05) but significantly less so (P < 0.05) for the conventionally treated than for the normal and intensively treated diabetic subjects. 15N recovery in urea was reduced for all groups after the second test meal (P < 0.05) but probably less effectively (P < 0.09) for the conventionally treated diabetic subjects. Metabolic adaptation to protein restriction may be less effective than normal in conventionally treated IDDM.

Effects of dietary protein restriction on glucose and insulin metabolism in normal and diabetic humans.

We determined whether the amount of protein in the diet can affect insulin requirements in subjects with diabetes mellitus and glucose metabolism in normal subjects. Seven normal-weight volunteers with uncomplicated, intensively controlled, type I (insulin-dependent) diabetes and 12 similar nondiabetic subjects were studied on a metabolic ward before and after consuming a maintenance-energy but protein-free diet for 10 days. Blood glucose levels of diabetic subjects were measured seven times daily in response to insulin administration by continuous subcutaneous infusion. The plasma glucose appearance rate (Ra) was measured in seven normal subjects and all diabetic subjects using a primed-continuous infusion of D-[6,6-2H2]glucose. After adaptation to the protein-restricted diet, diabetic subjects experienced a 30% decrease in average preprandial and average daily blood glucose concentrations (P < .01); this occurred despite a concurrent 25% decrease in both basal and bolus insulin dosages (P < .001). Protein restriction decreased the postabsorptive glucose Ra (P < .05) and insulin concentrations (P < .01) of normal subjects by 20%, and increased their fasting glucagon concentrations by 24% (P < .01). We conclude that severe protein restriction decreases insulin requirements in type I diabetes and fasting hepatic glucose output and basal insulin levels in normal subjects. This effect appears to be mediated in part by decreased hepatic gluconeogenesis, but a contributory influence of increased insulin sensitivity is not ruled out.

Evidence for different clinical subtypes of type 1 diabetes mellitus: a prospective study.

The purpose of this study was to determine whether the sex, age, severity of clinical presentation, presence of ICAs, IAs, and HLA-DR and DQ types could predict, in a cohort of newly-diagnosed diabetic children: (1) the duration of beta-cell function as measured by C-peptide response to a Sustacal meal; and (2) determine if those predictors could identify disease subtypes. A cohort of 170 consecutive patients was followed for 60 months after diagnosis. We found that age (0.0029), sex (0.0136), ICA (0.0001), presence of DKA (0.0070) and C-peptide peak at diagnosis (0.0000) significantly predicted the duration of residual beta-cell function over time. Furthermore, C-peptide secretion at diagnosis, presence of ICA, age and sex allowed the identification of three different prognostic groups with varying acceleration of beta-cell loss.

Different rates of conversion to IDDM in siblings of type 1 diabetic children: the Montreal family study.

This study was undertaken to analyze the risk of developing insulin-dependent diabetes (IDDM) in siblings of type 1 diabetic children. Islet-cell antibodies (ICA) were tested in 568 subjects, siblings of type 1 diabetic children. The subjects were followed prospectively for the conversion to clinical diagnosis of IDDM. As a result siblings who were islet cell antibody (ICA)+ positive at the time of diagnosis of the diabetic sibling (index case) had a significantly higher risk of developing IDDM than those who were ICA-. However, of the 19 siblings who developed IDDM, only 10 were ICA+ at the time of the first test but, 17 became ICA+ before diagnosis of IDDM. The interval between a positive test and the clinical diagnosis of IDDM varied between subjects (6-44 months, mean = 18.4 +/- 4.2 S.E. months) but it was less than 1 year in one subject. In addition to the higher risk of developing IDDM when ICA was positive, male sex and younger age of the subjects as well as young age of the index case and multiplex pedigrees were significant predictors of conversion to IDDM. The Cox's regression tree constructed using RECPAM identified three groups of varying rates of conversion to IDDM: (1) a group with the slowest progression characterized by ICA- and age of index case > 5 years or female sex (relative hazard = 1); (2) an intermediate progression group consisting of subjects who are ICA- and have both < 5 years of age and male sex (relative hazard = 8.78); (3) a group with the fastest progression consisting of subjects who are ICA+ (relative hazard = 31.45). From these results our data suggest that in addition to ICA, clinical markers such as age, sex and multiple pedigrees are also significant predictors of the rate of conversion to IDDM. Furthermore, screening for ICA in family intervention studies will have to be done frequently, perhaps yearly, and will have to be continued into adult life, particularly in ICA- subjects in order to identify the 85-90% of subjects who become ICA+ at the clinical diagnosis of IDDM.

Dietary disinhibition, perceived stress, and glucose control in young, type 1 diabetic women.

Examining the relationship of stress, dietary disinhibition, and blood glucose control in diabetic young women was the goal of this study. Sixty-five diabetic girls and women, ranging in age from 12 to 26 years, completed eating behaviors and perceived stress scales during regular clinic visits. Blood glucose control was assessed by concurrent glycosylated hemoglobin measurements. Multiple regression analyses indicated that high levels of perceived stress predicted dietary disinhibition and that within the age range studied, young women were more likely than early adolescent girls to perceive their life as stressful. Contrary to previous findings that failed to show that stress can indirectly affect glucose control by interfering with compliance behaviors, the present work indicated a Stress X Dietary Disinhibition interaction in predicting glucose control. Blood glucose control was poorest in those diabetic women who both perceived their lives as stressful and reported medium to high disinhibition. Blood glucose control was unrelated to stress in young women who reported low levels of disinhibition. These results have implications for the development of specific interventions for young diabetic women who perceive their lives as stressful and who may respond to stress by eating.

Factors predicting course of beta-cell function in IDDM.

OBJECTIVE: The purpose of this study was to determine whether the severity o clinical presentation, sex, age, HLA type, and the presence of IAs and ICAs could predict the variation of residual insulin secretion as measured by the serum C-peptide response to a Sustacal meal. RESEARCH DESIGN AND METHODS: A cohort of 151 newly diagnosed IDDM children (mean age 10.2 +/- 4.6 yr) was followed prospectively for 3 yr. Thirty-five patients (12 males, 23 females) were still secreting C-peptide after 36 mo. RESULTS: We found that age (P = 0.0001), sex (P = 0.003), presence of ICA (P = 0.006), severity of clinical presentation (P = 0.001), and symptom duration (P = 0.002) significantly predicted the rate of loss of C-peptide secretion. The risks of accelerated C-peptide disappearance decreased with increasing age, the risk ratios being 0.25 for the older group (greater than 12 yr) compared with the younger group (less than 6 yr) and 0.50 for the intermediate group (6-12 yr) compared with the younger group. The risk for the presence of ICA was 1.7, and the risk for males was 1.7 also. There was a significant negative correlation between ICA titers and C-peptide at 18 and 24 mo after diagnosis (P = 0.04). There were no significant differences in HbA1 values between patients who secreted C-peptide and those who did not. CONCLUSIONS: We conclude that younger age of onset, male sex, high titers of ICA, severe clinical presentation, and shorter symptom duration significantly predict accelerated rates of loss of C-peptide secretion.

Growth hormone response in very short children.

Growth hormone (GH) response to standardized exercise, L-DOPA/propranolol and a 6-h diurnal GH profile (GHP) were evaluated in twenty-three children with very short stature and abnormal growth velocities. Standardized exercise (Jones Stage I) was performed on a cycle ergometer at 53% of the maximum oxygen consumption (VO2max) for 20 min. VO2max was determined by an incremental progressive workload until exhaustion. The mean +/- SEM peak GH concentration (ng/ml) for each test was: exercise, 8.7 +/- 1.3; L-DOPA/P: 12.8 +/- 1.9 and GHP: 3 +/- 0.7. There was no statistical difference between exercise and L-DOPA/P peaks but both peaks were significantly higher than the peak observed during the profile. During exercise 14 of 23 patients had a GH response greater than 8 ng/ml. Two patients were found to be GH deficient. Therefore 16 of 23 patients (86%) had a result concordant with their final diagnosis. During the L-DOPA/P test 17 of 23 patients had a GH response greater than 8 ng/ml. By contrast only 6 of 23 patients had a positive response during GHP. Standardized exercise is as effective as L-DOPA/P as a stimulation test for growth hormone response in very short children with abnormal growth velocities. Exercise has the advantages of being physiological, having minimal side effects, and requiring fewer blood samples. In this population of children, exercise and L-DOPA/propranolol are significantly better than the 6-h growth hormone profile for assessing GH secretion.