The short-range order (SRO) in Pd78Cu6Si16 liquid was studied by high energy x-ray diffraction and ab initio molecular dynamics (MD) simulations. The calculated pair correlation functions at different temperatures agree well with the experimental results. The partial pair correlation functions from ab intio MD simulations indicate that Si atoms prefer to be uniformly distributed while Cu atoms tend to aggregate. By performing structure analysis using Honeycutt-Andersen index, Voronoi tessellation, and atomic cluster alignment method, we show that the icosahedron and face-centered cubic SRO increase upon cooling. The dominant SRO is the Pd-centered Pd9Si2 motif, namely the structure of which motif is similar to the structure of Pd-centered clusters in the Pd9Si2 crystal. The study further confirms the existence of trigonal prism capped with three half-octahedra that is reported as a structural unit in Pd-based amorphous alloys. The majority of Cu-centered clusters are icosahedra, suggesting that the presence of Cu is benefit to promote the glass forming ability.
Brain voltage activity displays distinct neuronal rhythms spanning a wide frequency range. How rhythms of different frequency interact – and the function of these interactions – remains an active area of research. Many methods have been proposed to assess the interactions between different frequency rhythms, in particular measures that characterize the relationship between the phase of a low frequency rhythm and the amplitude envelope of a high frequency rhythm. However, an optimal analysis method to assess this cross-frequency coupling (CFC) does not yet exist.
Here we describe a new procedure to assess CFC that utilizes the generalized linear modeling (GLM) framework.
We illustrate the utility of this procedure in three synthetic examples. The proposed GLM-CFC procedure allows a rapid and principled assessment of CFC with confidence bounds, scales with the intensity of the CFC, and accurately detects biphasic coupling.
Comparison with Existing Methods
Compared to existing methods, the proposed GLM-CFC procedure is easily interpretable, possesses confidence intervals that are easy and efficient to compute, and accurately detects biphasic coupling.
The GLM-CFC statistic provides a method for accurate and statistically rigorous assessment of CFC.
Phase-amplitude coupling; oscillations; theta; gamma
Owing to the more recent positive results with the anti-CD33 immunotoxin gemtuzumab ozogamicin, therapy against acute myeloid leukemias (AMLs) targeting CD33 holds many promises. Here, CD33 and CD123 expression on AML blasts was studied by flow cytometry in a cohort of 319 patients with detailed information on French–American–British/World Health Organization (FAB/WHO) classification, cytogenetics and molecular aberrations. AMLs of 87.8% express CD33 and would therefore be targetable with anti-CD33 therapies. Additionally, 9.4% of AMLs express CD123 without concomitant CD33 expression. Thus, nearly all AMLs could be either targeted via CD33 or CD123. Simultaneous presence of both antigens was observed in 69.5% of patients. Most importantly, even AMLs with adverse cytogenetics express CD33 and CD123 levels comparable to those with favorable and intermediate subtypes. Some patient groups with unfavorable alterations, such as FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, high FLT3-ITD mutant/wild-type ratios and monosomy 5 are even characterized by high expression of CD33 and CD123. In addition, blasts of patients with mutant nucleophosmin (NPM1) revealed significantly higher CD33 and CD123 expression pointing toward the possibility of minimal residual disease-guided interventions in mutated NPM1-positive AMLs. These results stimulate the development of novel concepts to redirect immune effector cells toward CD33- and CD123-expressing blasts using bi-specific antibodies or engineered T cells expressing chimeric antigen receptors.
The gap between what is known from clinical efficacy research and the systematic community translation of diabetes prevention programs is narrowing. During the past 5 years, numerous randomized and nonrandomized dissemination studies have evaluated the modified delivery of structured Diabetes Prevention Program (DPP) interventions in diverse real-world settings. Programs of sufficient dose and duration, implemented with fidelity, have reported weight losses in the range of 4%–7% with associated improvements in cardiometabolic risk factors at 6 and 12 months from baseline. The current article describes some of the experiences and perspectives of a team of University of Pittsburgh researchers as they have engaged in these efforts.
Evidence from varied community settings has shown that the Group Lifestyle Balance (GLB) Program and other adaptations of the Diabetes Prevention Program (DPP) intervention are effective in lowering diabetes risk. Most DPP data originated from studies of pre-diabetic whites, with only sparse evidence of the effect of DPP in African Americans (AAs) in community settings. This paper describes the design, methods, baseline characteristics and cost effective measures, of a single-blinded, cluster- randomized trial of a faith-based adaptation of the GLB program, Fit Body and Soul (FBAS). The major aims are to test efficacy and cost utility of FBAS in twenty AA churches. Randomization occurred at the church level and 604 AA overweight/obese (BMI≥25 kg/m2) adults with fasting plasma glucose range from normal to pre-diabetic received either FBAS or a health-education comparison program. FBAS is a group-based, multi-level intervention delivered by trained church health advisors (health professionals from within the church), with the goal of ≥7% weight loss, achieved through increasing physical activity, healthy eating and behavior modification. The primary outcome is weight change at 12-weeks post intervention. Secondary outcomes include hemoglobin A1C, fasting plasma glucose, waist circumference, blood pressure, physical activity level, quality of life measures, and cost-effectiveness. FBAS is the largest known cohort of AAs enrolled in a faith-based DPP translation. Reliance on health professionals from within the church for program implementation and the cost analysis are unique aspects of this trial. The design provides a model for faith-based DPPs and holds promise for program sustainability and widespread dissemination.
African-American; church; cluster; translation research; diabetes prevention; obesity
Determination of atomic-scale crystal structure for nanostructured intermetallic alloys, such as magnetic alloys containing Al, Ni, Co (alnico) and Fe, is crucial for understanding physical properties such as magnetism, but technically challenging due to the small interatomic distances and the similar atomic numbers. By applying energy-dispersive X-ray spectroscopy (EDS) mapping to the study of two intermetallic phases of an alnico alloy resulting from spinodal decomposition, we have determined atomic-scale chemical composition at individual lattice sites for the two phases: one is the B2 phase with Fe0.76Co0.24 -Fe0.40Co0.60 ordering and the other is the L21 phase with Ni0.48Co0.52 at A-sites, Al at BΙ-sites and Fe0.20Ti0.80 at BΙΙ-sites, respectively. The technique developed through this study represents a powerful real-space approach to investigate structure chemically at the atomic scale for a wide range of materials systems.
Few studies have prospectively investigated whether early-life exposures are associated with pre-adolescent eating attitudes.
The objective of this study is to prospectively investigate associations of parental smoking, alcohol use, marital status, measures of maternal satisfaction, self-reported parental body mass index (BMI) and clinically measured childhood BMI, assessed between birth and 6.5 years, with problematic eating attitudes at 11.5 years.
Observational cohort analysis nested within the Promotion of Breastfeeding Intervention Trial, a cluster-randomised trial conducted in 31 maternity hospitals and affiliated polyclinics in Belarus. Our primary outcome was a Children's Eating Attitudes Test (ChEAT) score ⩾22.5 (85th percentile), an indicator of problematic eating attitudes. We employed multivariable mixed logistic regression models, which allow inference at the individual level. We also performed instrumental variable (IV) analysis using parents' BMIs as instruments for the child's BMI, to assess whether associations could be explained by residual confounding or reverse causation.
Of the 17 046 infants enrolled between 1996 and 1997 across Belarus, 13 751 (80.7%) completed the ChEAT test at 11.5 years.
In fully adjusted models, overweight children at age 6.5 years had a 2.14-fold (95% confidence interval (CI): 1.82, 2.52) increased odds of having ChEAT scores ⩾85th percentile at age 11.5 years, and those who were obese had a 3.89-fold (95% CI: 2.95, 5.14) increased odds compared with normal-weight children. Children of mothers or fathers who were themselves overweight or obese were more likely to score ⩾85th percentile (P for trend ⩽0.001). IV analysis was consistent with a child's BMI causally affecting future eating attitudes. There was little evidence that parental smoking, alcohol use, or marital status or maternal satisfaction were associated with eating attitudes.
In our large, prospective cohort in Belarus, both parental and childhood overweight and obesity at 6.5 years were associated with pre-adolescent problematic eating attitudes 5 years later.
body mass index; maternal satisfaction; parental smoking and alcohol use; problematic eating attitudes; cohort study; instrumental variable analysis
The structural description of disordered systems has been a longstanding challenge in physical science. We propose an atomic cluster alignment method to reveal the development of three-dimensional topological ordering in a metallic liquid as it undercools to form a glass. By analyzing molecular dynamic (MD) simulation trajectories of a Cu64.5Zr35.5 alloy, we show that medium-range order (MRO) develops in the liquid as it approaches the glass transition. Specifically, around Cu sites, we observe “Bergman triacontahedron” packing (icosahedron, dodecahedron and icosahedron) that extends out to the fourth shell, forming an interpenetrating backbone network in the glass. The discovery of Bergman-type MRO from our order-mining technique provides unique insights into the topological ordering near the glass transition and the relationship between metallic glasses and quasicrystals.
We estimated the heritability of individual differences in beta cell function after a mixed meal test designed to assess a wide range of classical and model-derived beta cell function parameters.
A total of 183 healthy participants (77 men), recruited from the Netherlands Twin Register, took part in a 4 h protocol, which included a mixed meal test. Participants were Dutch twin pairs and their siblings, aged 20 to 49 years. All members within a family were of the same sex. Insulin sensitivity, insulinogenic index, insulin response and postprandial glycaemia were assessed, as well as model-derived parameters of beta cell function, in particular beta cell glucose sensitivity and insulin secretion rates. Genetic modelling provided the heritability of all traits. Multivariate genetic analyses were performed to test for overlap in the genetic factors influencing beta cell function, waist circumference and insulin sensitivity.
Significant heritabilities were found for insulinogenic index (63%), beta cell glucose sensitivity (50%), insulin secretion during the first 2 h postprandial (42–47%) and postprandial glycaemia (43–52%). Genetic factors influencing beta cell glucose sensitivity and insulin secretion during the first 30 postprandial min showed only negligible overlap with the genetic factors that influence waist circumference and insulin sensitivity.
The highest heritability for postprandial beta cell function was found for the insulinogenic index, but the most specific indices of heritability of beta cell function appeared to be beta cell glucose sensitivity and the insulin secretion rate during the first 30 min after a mixed meal.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-011-2060-5) contains supplementary material, which is available to authorised users.
Gastro-entero pancreatic function; Genetics of type 2 diabetes; Human; Insulin secretion; Insulin sensitivity; Metabolic physiology
We assessed the cost-effectiveness of a community-based, modified Diabetes Prevention Program (DPP) designed to reduce risk factors for type 2 diabetes and cardiovascular disease.
We developed a Markov decision model to compare costs and effectiveness of a modified DPP intervention with usual care during a 3-year period. Input parameters included costs and outcomes from 2 projects that implemented a community-based modified DPP for participants with metabolic syndrome, and from other sources. The model discounted future costs and benefits by 3% annually.
At 12 months, usual care reduced relative risk of metabolic syndrome by 12.1%. A modified DPP intervention reduced relative risk by 16.2% and yielded life expectancy gains of 0.01 quality-adjusted life-years (3.67 days) at an incremental cost of $34.50 ($3,420 per quality-adjusted life-year gained). In 1-way sensitivity analyses, results were sensitive to probabilities that risk factors would be reduced with or without a modified DPP and that patients would enroll in an intervention, undergo testing, and acquire diabetes with or without an intervention if they were risk-factor–positive. Results were also sensitive to utilities for risk-factor–positive patients. In probabilistic sensitivity analysis, the intervention cost less than $20,000 per quality-adjusted life-year gained in approximately 78% of model iterations.
We consider the modified DPP delivered in community and primary care settings a sound investment.
The aim of this study was to investigate whether the final displacement of conservatively treated distal radius fractures can be predicted after primary reduction. We analysed the radiographic documents of 311 patients with a conservatively treated distal radius fracture at the time of injury, after reduction and after bony consolidation. We measured the dorsal angulation (DA), the radial angle (RA) and the radial shortening (RS) at each time point. The parameters were analysed separately for metaphyseally “stable” (A2, C1) and “unstable” (A3, C2, C3) fractures, according to the AO classification system. Spearman’s rank correlations and regression functions were determined for the analysis. The highest correlations were found for the DA between the time points ‘reduction’ and ‘complete healing’ (r = 0.75) and for the RA between the time points ‘reduction’ and ‘complete healing’ (r = 0.80). The DA and the RA after complete healing can be predicted from the regression functions.
The Compress® implant (Biomet, Warsaw, IN) is an innovative device developed to enable massive endoprosthetic fixation through the application of compressive forces at the bone-implant interface. This design provides immediate, stable anchorage and helps to avoid the long-term complication of aseptic loosening secondary to stress shielding and particle-induced osteolysis seen in conventional, stemmed megaprostheses. The purpose of our study was to evaluate the in vivo biological effects of the high compressive forces attained. Twelve consecutive Compress® patients undergoing revision surgery for infection, periprosthetic fracture, or local tumour recurrence were reviewed in order to exclude the possibility of osteonecrosis at the prosthetic interface. Compressive forces ranged from 400–800 lb. Duration of implantation averaged 3.3 years (range 0.4–12.2 years). Two patients with infection demonstrated loosening at the bone-prosthetic interface; otherwise, there was no radiographic evidence of prosthetic failure in any of the patients. No patient demonstrated histological evidence of osteonecrosis. In fact, new woven bone and other findings consistent with viable bone were noted in all of the retrieved specimens.
Methods: People originating from Surinam (n = 798) and the Netherlands Antilles (n = 227) were recruited in order to study the heterosexual spread of HIV within ethnic groups. Log binomial regression was used to study determinants for homeland travel over the past 5 years; logistic regression was used to study determinants of unprotected sex on these visits.
Results: Of the migrants, 38% of men and 42% of women visited their homeland. Visits were most likely among men who had lived ⩾7 years in the Netherlands, were employed, had a high educational level and were/had been married. For women, visiting was associated with older age and living in the Netherlands for ⩾8 years. Of migrants visiting their homeland, 47% of men and 11% of women acquired a local sexual partner. For male travellers, Surinamese origin (adjusted OR 10.66; 95% CI 1.72 to 104.48) and a history of ⩾1 sexually transmitted infection (STI) (adjusted OR 12.51; 95% CI 3.75 to 46.95) were associated with having unprotected sex with local partners. For women, having >1 partner in the past 5 years (OR 13.57; 95% CI 2.57 to 250.28) was associated with unprotected sex with local partners.
Conclusion: Migrants are at substantial risk for HIV and STIs while visiting their homeland. It is important to reach migrants, who are likely to engage in unprotected sex during visits, for pretravel health education. Additional research on risk behaviour in the homeland and the Netherlands is needed to identify migrants with high risk behaviour.
To evaluate barriers to and strategies for medication adherence and predictors of adherence and the primary outcome in the Diabetes Prevention Program (DPP).
RESEARCH DESIGN AND METHODS
Within a randomized, controlled primary prevention study for type 2 diabetes, we collected data on study medication adherence, its predictors, and health outcomes in 27 clinical centers across mainland U.S. and Hawaii. Medication arm participants included 2,155 adults with impaired glucose tolerance randomly assigned to either metformin or matched placebo treatment arms. Structured interviews were used to promote medication adherence and to collect data regarding adherence. Adherence was measured by pill count. The primary DPP outcome of type 2 diabetes was assessed by fasting plasma glucose and oral glucose tolerance test.
Older age-groups were more adherent than the youngest group (P = 0.01) in the metformin group. The most frequently reported barrier to adherence was “forgetting” (22%). Women reported more adverse effects of metformin (15 vs. 10%, P = 0.002) in the metformin group. Odds of nonadherence increased as participants reported more than one barrier (odds ratio 19.1, P < 0.001). Odds of adherence increased as participants reported multiple strategies to take medication (2.69, P < 0.0001). There was a 38.2% risk reduction for developing diabetes for those adherent to metformin compared with those adherent to placebo (P < 0.0003).
DPP medication adherence results are unique in primary prevention for a chronic disease in a large multiethnic sample. Our finding that adherence was associated with risk reduction for diabetes supports the development of brief interventions in clinical settings where medication adherence is a challenge.
DPP, Diabetes Prevention Program
Aseptic loosening is well known following endoprosthetic replacement (EPR) using cemented intramedullary stems (CISs). The Compress® (CPS) implant uses a novel spring system, achieving immediate, high compression fixation that induces bone hypertrophy and avoids stress shielding. We compared 26 oncologic distal femoral CPS patients treated at the University of California, San Francisco (UCSF, USA) with 26 matched CIS patients from the Royal Orthopaedic Hospital, Birmingham (ROH, UK). The predominant diagnosis was osteosarcoma. Each centre had only one device-related prosthetic failure. In the short term these results show CPS to be safe and effective. We await longer follow-up to assess the ongoing potential for prosthetic failure.
Background/aim: Alterations of the immune system may have a role in thrombogenesis. Artery sites occluded with thrombi apparently release pro-inflammatory cytokines. Non-arteritic anterior ischaemic optic neuropathy (NAION) results from occlusion of the blood supply to the optic nerve. The aim of this study was to analyse levels of pro-inflammatory cytokines in patients with acute event of NAION.
Methods: Study participants included 10 patients (12 eyes) with NAION and 20 age matched controls with the same risk factors for atherosclerosis disease. Peripheral blood samples were obtained immediately at the acute onset of NAION. Plasma interleukin 8 (IL-8), IL-6, and tumour necrosis factor alpha (TNF-α) levels were measured immediately following diagnosis and during the follow up intervals.
Results: The plasma levels of IL-8 were significantly higher in NAION patients at the time of diagnosis in comparison to the control group (p = 0.002), and decreased during the follow up period (6–12 months) (p = 0.05). There were no differences in plasma levels of IL-6 and TNF-α between NAION patients and controls, either in the acute phase or during the follow up period.
Conclusion: Plasma levels of IL-8 are elevated during the acute phase of NAION, but not IL-6 and TNF-α. These elevated levels are in accordance with other acute vascular thrombosis. The clinical significance of these findings should be further evaluated.
interleukins; tumour necrosis factor; anterior ischaemic optic neuropathy
Simultaneous measurement of intramuscular pressure (IMP), tissue oxygen partial pressure (pO2) and EMG fatigue parameters in the multifidus muscle during a fatigue-inducing sustained muscular contraction. The study investigated the following hypotheses: (1) Increases in IMP result in tissue hypoxia; (2) Tissue hypoxia is responsible for loss of function in the musculature. The nutrient supply to muscle during muscle contraction is still not fully understood. It is assumed that muscle contraction causes increased tissue pressure resulting in compromised perfusion and tissue hypoxia. This tissue hypoxia, in turn, leads to muscle fatigue and therefore to loss of function. To the authors’ knowledge, no study has addressed IMP, pO2 and EMG fatigue parameters in the same muscle to gain a deeper sight into muscle perfusion during contraction. As back muscles need to have a constant muscular tension to maintain trunk stability during stance and locomotion, muscle fatigue due to prolonged contraction-induced hypoxia could be an explanation for low back pain. Sixteen healthy subjects performed an isometric muscular contraction exercise at 60% of maximum force until the point of localized muscular fatigue. During this exercise, the individual changes of IMP, pO2 and the median frequency (MF) of the surface EMG signal of the multifidus muscle were recorded simultaneously. In 12 subjects with a documented increase in intramuscular pressure, only five showed a decrease in tissue oxygen partial pressure, while this parameter remained unchanged in six other subjects and even increased in one. A fall in tissue pO2 was associated with a drop in MF in only five subjects, while there was no correlation between these parameters in the other 11 subjects. To summarize, an increase in IMP correlated with a decrease in pO2 and a drop in MF in only five out of 16 subjects. High intramuscular pressure values are not always associated with a hypoxia in muscle tissue. Tissue hypoxia is not automatically associated with a median frequency shift in the EMG signal’s power spectrum.
Tissue oxygenation; Muscular fatigue; Intramuscular pressure; Multifidus muscle; Isometric back extension
High dose rate (HDR) endobronchial brachytherapy is a
palliative treatment for symptomatic airway obstruction by malignant tumours. We report a novel use of HDR brachytherapy for treating non-malignant bronchial obstruction. The patient had a metal stent placed in a reconstructed airway after a bronchial tear to ensure patency. Granulation tissue formation in and around the stent caused
symptomatic occlusion of the airway, necessitating multiple laser
applications. A single treatment of HDR brachytherapy (1000 cGy) was
delivered following laser therapy. The patient remains well 15 months
after treatment with no evidence of recurrent granulation tissue
formation on bronchoscopy. HDR brachytherapy is an effective treatment
for non-malignant airway obstruction.
OBJECTIVE: To examine the value of two kinds of patient-level dat a (cost and diagnoses) for identifying a very small subgroup of a general population with high future costs that may be mitigated with medical management. DATA SOURCES: The study used the MEDSTAT Market Scan (R) Research Database, consisting of inpatient and ambulatory health care encounter records for individuals covered by employee- sponsored benefit plans during 1997 and 1998. STUDY DESIGN: Prior cost and a diagnostic cost group (DCG) risk model were each used with 1997 data to identify 0.5-percent-sized "top groups" of people most likely to be expensive in 1998. We compared the distributions of people, cost, and diseases commonly targeted for disease management for people in the two top groups and, as a bench mark, in the full population. PRINCIPAL FINDINGS: the prior cost- and DCG-identified top groups overlapped by only 38 percent. Each top group consisted of people with high year-two costs and high rates of diabetes, heart failure, major lung disease, and depression. The DCG top group identified people who are both somewhat more expensive ($27,292 vs. $25,981) and more likely ( 49.4 percent vs. 43.8 percent ) th an the prior-cost top group to have at least one of the diseases commonly targeted for disease management. The overlap group average cost was $46,219. CONCLUSIONS: Diagnosis-based risk models are at least as powerful as prior cost for identifying people who will be expensive. Combined cost and diagnostic data are even more powerful and more operation ally useful, especially because the diagnostic information identifies the medical problems that may be managed to achieve better out comes and lower costs.
The dorsal approach is increasingly preferred in the surgical treatment of vertebral fractures. However, the access and the implant's position cause muscle loss, which can lead to instability and a reduced capacity for rehabilitation. Morphological factors (bones, intervertebral discs) are typically blamed for chronic pain syndromes in the literature, while less importance is attached to functional factors (muscles). The objective of this study was therefore to investigate the isolated influence of dorsal spinal instrumentation on the back muscles by means of electromyography (EMG). A total of 32 patients with conditions after dorsal spondylodesis following the fracture of a vertebral body and 32 subjects with healthy backs were enrolled in this study. The EMG signal was recorded in three different muscle groups during isometric extension exercise. The evaluation was performed by comparing the mean rectified amplitudes of the three muscle groups in the patients and controls. The patients had significantly lower amplitudes in the multifidus muscle (MF) and significantly higher amplitudes in the iliocostal muscle (IL). Patients with severe pain were found to have lower electric muscle potentials in all investigated muscle groups than patients with mild pain. The muscle damage which was established in the multifidus muscle is compensated by increased activity in the iliocostal muscle. On the basis of anatomical considerations, the damage pattern can be identified as having been caused by surgery. It is extremely unlikely that trauma is the cause.
Lumbar Spine Surgery Muscle Surface EMG Vertebral fracture
Neurofibromatosis has been known to involve blood vessels
throughout the body. Pulmonary involvement with interstitial fibrosing alveolitis has been described but no case of pulmonary vascular involvement has been reported to date. A 51 year old patient with cutaneous neurofibromatosis is described who presented with severe pulmonary hypertension and radiographic, scintigraphic, and
angiographic evidence of chronic thromboembolic pulmonary
hypertension. Severe intimal fibrosis consistent with vascular
involvement with neurofibromatosis was found on endarterectomy with
no evidence of pulmonary thromboembolism. Neurofibromatosis of
pulmonary arteries should be considered as a possible cause of