Cost of achieving HbA1c and weight loss treatment targets with IDegLira vs insulin glargine U100 plus insulin aspart in the USA.

BACKGROUND: Compared with basal-bolus insulin therapy (insulin glargine U100 plus insulin aspart), IDegLira has been shown to be associated with similar improvements in HbA1c, with superior weight loss and reduced hypoglycemia in patients with type 2 diabetes. The present analysis evaluated the cost per patient with type 2 diabetes achieving HbA1c-focused and composite treatment targets with IDegLira and insulin glargine U100 plus insulin aspart (≤4 times daily). METHODS: The proportions of patients achieving treatment targets were obtained from the treat-to-target, non-inferiority DUAL VII study (NCT02420262). The annual cost per patient achieving target (cost of control) was analyzed from a US healthcare payer perspective. The annual cost of control was assessed for eight prespecified endpoints and four post-hoc endpoints. RESULTS: The number needed to treat to bring one patient to targets of HbA1c <7.0% and HbA1c ≤6.5% was similar with IDegLira and insulin glargine U100 plus insulin aspart. However, when weight gain and/or hypoglycemia were included, the number needed to treat was lower with IDegLira. IDegLira and insulin glargine U100 plus insulin aspart had similar costs of control for HbA1c <7.0%. However, cost of control values were substantially lower with IDegLira when the more stringent target of HbA1c ≤6.5% was used, and when patient-centered outcomes of hypoglycemia risk and impact on weight were included. CONCLUSION: IDegLira was shown to be a cost-effective treatment vs insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic targets on basal insulin in the USA.

Effective Vaccination Policies.

We present a framework for modeling the spread of pathogens throughout a population and generating policies that minimize the impact of those pathogens on the population. This framework is used to study the spread of human viruses between cities via airplane travel. It combines agent-based simulation, mathematical analysis, and an Evolutionary Algorithm (EA) optimizer. The goal of this study is to develop tools that determine the optimal distribution of a vaccine supply in the model. Using plausible benchmark vaccine allocation policies of uniform and proportional distribution, we compared their effectiveness to policies found by the EA. We then designed and tested a new, more effective policy which increased the importance of vaccinating smaller cities that are flown to more often. This "importance factor" was validated using U.S. influenza data from the last four years.

Phase II trial of imatinib mesylate in patients with metastatic melanoma.

Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.

The astrobiology primer: an outline of general knowledge--version 1, 2006.

The Astrobiology Primer has been created as a reference tool for those who are interested in the interdisciplinary field of astrobiology. The field incorporates many diverse research endeavors, but it is our hope that this slim volume will present the reader with all he or she needs to know to become involved and to understand, at least at a fundamental level, the state of the art. Each section includes a brief overview of a topic and a short list of readable and important literature for those interested in deeper knowledge. Because of the great diversity of material, each section was written by a different author with a different expertise. Contributors, authors, and editors are listed at the beginning, along with a list of those chapters and sections for which they were responsible. We are deeply indebted to the NASA Astrobiology Institute (NAI), in particular to Estelle Dodson, David Morrison, Ed Goolish, Krisstina Wilmoth, and Rose Grymes for their continued enthusiasm and support. The Primer came about in large part because of NAI support for graduate student research, collaboration, and inclusion as well as direct funding. We have entitled the Primer version 1 in hope that it will be only the first in a series, whose future volumes will be produced every 3-5 years. This way we can insure that the Primer keeps up with the current state of research. We hope that it will be a great resource for anyone trying to stay abreast of an ever-changing field.

'Active' filters for upgrading phosphorus removal from pond systems.

This paper investigates limestone and iron slag filters as an upgrade option for phosphorus removal from wastewater treatment ponds. A review of 'active' filter technology and the results from laboratory and field research using packed columns of the different media is presented. It is shown that both limestone and iron slag can remove phosphorus but highlights that different types of limestone give markedly different performance. Filter performance appears to be improved by increasing temperature and by the presence of algae, presumably because of its tendency to elevate pH. Performance is related to hydraulic retention time (HRT), but this relationship is not linear, particularly at low HRTs. Importantly for future research, the results from field-testing with pond effluent show significant differences compared to those obtained when using a synthetic feed in the laboratory. For the iron slag filter, higher performance was observed in the field (72% in field vs. 27% in laboratory, at a 12 hour-HRT), while the opposite was observed for the limestone (64% in laboratory vs. 18% in field, at a 12-hour HRT).

Exciting chaos with noise: unexpected dynamics in epidemic outbreaks.

In this paper, we identify a mechanism for chaos in the presence of noise. In a study of the SEIR model, which predicts epidemic outbreaks in childhood diseases, we show how chaotic dynamics can be attained by adding stochastic perturbations at parameters where chaos does not exist apriori. Data recordings of epidemics in childhood diseases are still argued as deterministic chaos. There also exists noise due to uncertainties in the contact parameters between those who are susceptible and those who are infected, as well as random fluctuations in the population. Although chaos has been found in deterministic models, it only occurs in parameter regions that require a very large population base or other large seasonal forcing. Our work identifies the mechanism whereby chaos can be induced by noise for realistic parameter regions of the deterministic model where it does not naturally occur.

The role of the globus pallidus D2 subfamily of dopamine receptors in pallidal immediate early gene expression.

The globus pallidus plays an important role in basal ganglia circuitry, representing the first relay nucleus of the 'indirect pathway' of striatal efferents. In contrast to the well-characterized actions of dopamine on striatal neurons, the functional role of the dopamine innervation of globus pallidus is less well understood. Previous research showed that systemic administration of either a dopamine D2 receptor antagonist or combined dopamine D1 and D2 receptor agonists induces Fos, the protein product of the immediate early gene c-fos, in neurons of globus pallidus [Ruskin and Marshall (1997) Neuroscience 81, 79-92]. To determine whether the ability of the D2 receptor antagonist, sulpiride, to induce Fos in rat pallidal neurons is mediated by D2-like receptors in striatum or globus pallidus, intrastriatal or intrapallidal sulpiride infusions were conducted. The diffusion of intrastriatal sulpiride was estimated by measuring this antagonist's competition for N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced D2 receptor inactivation. The phenotype of the striatal neurons expressing Fos after intrastriatal infusion was assessed by combining Fos immunocytochemistry with D2 receptor mRNA in situ hybridization. Intrastriatal infusions of (-)-sulpiride (10-200 ng) dose-dependently increased the number of striatal cells expressing Fos; and the Fos-immunoreactive striatal cells were D2 receptor mRNA-expressing, the same population in which systemic D2 receptor antagonists induce Fos. Intrastriatal infusions of high (5 microg), but not low (10-200 ng), (-)-sulpiride doses also induced Fos in globus pallidus cells but the sulpiride appeared to spread to the globus pallidus. Direct intrapallidal infusions of (-)-sulpiride (50-100 ng) dose-dependently induced Fos in globus pallidus with minimal influence on striatum or other basal ganglia structures. Using sensitive in situ hybridization conditions, prominent labeling of D2 receptor mRNA was evident in globus pallidus. D2 receptor mRNA was densest in a lateral 200 microm wide band that follows the curvature of the pallidal/striatal boundary. Cellular analysis revealed silver clusters associated with D2 receptor mRNA labeling over globus pallidus neurons that were immunoreactive for neuron-specific nuclear protein. These results strongly suggest that the dopaminergic innervation of globus pallidus, acting through D2-like receptors internal to this structure, can control gene expression in pallidal neurons.

Methods for short time series analysis of cell-based biosensor data.

This paper describes two approaches for sensing changes in spiking cells when only a limited amount of spike data is available, i.e., dynamically constructed local expansion rates and spike area distributions. The two methods were tested on time series from cultured neuron cells that exhibit spiking both autonomously and in the presence of periodic stimulation. Our tested hypothesis was that minute concentrations of toxins could affect the local statistics of the dynamics. Short data sets having relatively few spikes were generated from experiments on cells before and after being treated with a small concentration of channel blocker. In spontaneous spiking cells, local expansion rates show a sensitivity that correlates with channel concentration level, while stimulated cells show no such correlation. Spike area distributions on the other hand showed measurable differences between control and treated conditions for both types of spiking, and a much higher degree of sensitivity. Because these methods are based on analysis of short time series analysis, they might provide novel means for cell drug and toxin detection.

Child custody mediation and litigation: custody, contact, and coparenting 12 years after initial dispute resolution.

Long-term follow-up data were obtained on families who had been randomly assigned to mediate or litigate their child custody disputes. In comparison with families who litigated custody, nonresidential parents who mediated were more involved in multiple areas of their children's lives, maintained more contact with their children, and had a greater influence in coparenting 12 years after the resolution of their custody disputes. The increased involvement of nonresidential parents who mediated did not lead to an associated increase in coparenting conflict. Parents who mediated also made more changes in their children's living arrangements over the years. For the most part, the changes apparently reflect increased cooperation and flexibility. Satisfaction declined for parents (especially fathers) in both groups over time, but fathers remained much more satisfied if they mediated rather than litigated custody. Few differences in satisfaction were found between mothers in the 2 groups. The 12-year follow-up data indicate that, even in contested cases. mediation encourages both parents to remain involved in their children's lives after divorce without increasing coparenting conflict.

Distress among young adults from divorced families.

Researchers find that most children from divorced families function normally, but some clinicians assert that young people are disturbed even many years after a divorce. These accounts may be less discrepant than they appear, because research typically focuses on notably problematic behavior (disorder), whereas case studies emphasize more subtle inner turmoil (distress). In Study 1 college students reported painful feelings, beliefs, and memories about their parents divorce on a reliable new measure, but they also reported accepting the divorce and having few psychological symptoms. Distress about family life was greater among students from divorced than from married families. Study 2 replicated these findings in a community sample of young people from low-income divorced families. In both studies, greater distress was associated with children's residence, frequency of contact with fathers, interparental conflict, and psychological symptoms.

Surface texturing and coating of biomaterial implants: effects on tissue integration and fibrosis.

To determine whether texturing and coating have additive effects in promoting tissue integration and inhibiting fibrosis, we evaluated smooth silicone rubber (SSR), textured silicone rubber (TSR), porous silicone rubber (PSR), expanded polytetrafluoroethylene (ePTFE), and porous polyurethane (PPU) subcutaneous implants in eight minipigs. Some of the implants were coated with type IV collagen (Col) and/or fibronectin (Fn). At 6 months, we removed the implants and examined them microscopically. Texturing was more important than Col and Fn in reducing fibrosis and inflammation. The PSR yielded the best response, including reduced fibrosis and inflammation, satisfactory adherence, and no dystrophic mineralization.

Dopaminergic modulation of pallidal preproenkephalin mRNA.

The present study examines dopaminergic regulation of neuropeptide gene expression within a relatively poorly characterized population of cells, the preproenkephalin (PPE) mRNA containing neurons of the globus pallidus (GP). Rats that received 6-hydroxydopamine (6-OHDA) lesions or repeated D1 or D2 antagonist administration were compared to control animals. One month after 6-OHDA lesions, PPE mRNA was elevated in the GP ipsilateral to the lesion, with a smaller elevation also being observed in the contralateral GP. Repeated administration of eticlopride, but not SCH 23390, also resulted in elevated PPE mRNA expression in the GP. These data reveal a novel effect of decreased dopamine transmission on the GP, and draw attention to this subpopulation of pallidal neurons.

An overview of the nature, causes, and consequences of abusive family relationships. Toward differentiating maltreatment and violence.

Despite gaps in research, this review argues for distinguishing family maltreatment from family violence, a differentiation between minimal or moderate abuse and serious endangerment, physical injury, or sexual violation. Most acts now defined as violent or abusive are moderate, and stressful life circumstances contribute to their development. Research suggests that abuse may develop through multiple pathways. The consequences of abuse appear to be general, but more commonalities may be found by examining more subtle and complex effects. Many interventions have attempted to prevent or treat family violence and its consequences, and several show promise. More systematic research is needed, but several changes in intervention seem warranted now. For instance, (a) mental health professionals should not be required to report maltreatment while a family is engaged in therapy; (b) the social service system needs to rediscover its roots in supporting families under stress, including in cases of moderate maltreatment; and (c) swift and decisive legal intervention is needed in cases of serious family violence.

Practical and emotional consequences of parental divorce.

This review explores divorce as a risk factor for psychological problems among children and adolescents and the difficult emotional and practical transitions it creates for them. The authors provide helpful suggestions for primary care pediatricians on how best to assist their adolescent patients and their families in dealing with the transition.

Efficient cw end-pumped, end-cooled Nd:YVO(4) diode-pumped laser.

Using a novel end-pumped, end-cooled geometry, we demonstrated a Nd:YVO(4) cw laser that produces close to 2 W of single-mode output when pumped by a high-brightness 100-mum-core diode fiber source. An optical-optical conversion efficiency of 49% was obtained. Beam quality was found to be nearly diffraction-limited (M(2) = 1.08) and independent of pumping power.

Wound infection rates in dogs and cats after use of cotton muslin or disposable impermeable fabric as barrier material: 720 cases (1983-1989).

A retrospective study involving 720 dogs and cats that underwent a variety of elective surgical procedures was done to compare the effectiveness of reusable cotton barrier materials with that of a commercially available disposable barrier system for prevention of wound infection. The overall wound infection rate, using cotton barrier materials, was 3.1% and for disposable materials, was 4.4%. The difference between groups was not significant.

Establishment of genital tract infection in the CF-1 mouse by intravaginal inoculation of a human oculogenital isolate of Chlamydia trachomatis.

A human oculogenital strain of Chlamydia trachomatis was instilled intravaginally in the outbred CF-1 mouse to establish cervical infection. The mice were neither hormonally nor immunologically manipulated before inoculation. Duration of chlamydial excretion varied from two to ten days. In the culture-positive animals, IgG and IgM antibody titers were elevated in 38% and 17%, respectively. Neither intracytoplasmic inclusions nor elementary bodies of C. trachomatis were detected in genital tissues. Infection was limited primarily to the cervix and only rarely extended into the uterus. Chlamydial infection could only be established during specific periods of the estrus cycle (metestrus-2, diestrus, and proestrus; P less than .001), stages when leukocytes are present in the vaginal smear. Thus, chlamydial infection of the cervix is cycle-dependent in the mouse. In summary, infection of the cervix of the mouse has been established with a human oculogenital strain of C. trachomatis and may be useful as a model of human chlamydial cervicitis.