Association of types of diabetes and insulin dependency on birth outcomes.

BACKGROUND: Diabetes rates among pregnant women in the United States have been increasing and are associated with adverse pregnancy outcomes. AIM: To investigate differences in birth outcomes (preterm birth, macrosomia, and neonatal death) by diabetes status. METHODS: Cross-sectional design, using linked Missouri birth and death certificates (singleton births only), 2010 to 2012 (n = 204057). Exposure was diabetes (non-diabetic, pre-pregnancy diabetes-insulin dependent (PD-I), pre-pregnancy diabetes-non-insulin dependent (PD-NI), gestational diabetes- insulin dependent (GD-I), and gestational diabetes-non-insulin dependent (GD-NI)]. Outcomes included preterm birth, macrosomia, and infant mortality. Confounders included demographic characteristics, adequacy of prenatal care, body mass index, smoking, hypertension, and previous preterm birth. Bivariate and multivariate logistic regression assessed differences in outcomes by diabetes status. RESULTS: Women with PD-I, PD-NI, and GD-I remained at a significantly increased odds for preterm birth (aOR 2.87, aOR 1.77, and aOR 1.73, respectively) and having a very large baby [macrosomia] (aOR 3.01, aOR 2.12, and aOR 1.96, respectively); in reference to non-diabetic women. Women with GD-NI were at a significantly increased risk for macrosomia (aOR1.53), decreased risk for their baby to die before their first birthday (aOR 0.41) and no difference in risk for preterm birth in reference to non-diabetic women. CONCLUSION: Diabetes is associated with the poor birth outcomes. Clinical management of diabetes during pregnancy and healthy lifestyle behaviors before pregnancy can reduce the risk for diabetes and poor birth outcomes.

An engineered ligand trap inhibits leukemia inhibitory factor as pancreatic cancer treatment strategy.

Leukemia inhibitory factor (LIF), a cytokine secreted by stromal myofibroblasts and tumor cells, has recently been highlighted to promote tumor progression in pancreatic and other cancers through KRAS-driven cell signaling. We engineered a high affinity soluble human LIF receptor (LIFR) decoy that sequesters human LIF and inhibits its signaling as a therapeutic strategy. This engineered 'ligand trap', fused to an antibody Fc-domain, has ~50-fold increased affinity (~20 pM) and improved LIF inhibition compared to wild-type LIFR-Fc, potently blocks LIF-mediated effects in pancreatic cancer cells, and slows the growth of pancreatic cancer xenograft tumors. These results, and the lack of apparent toxicity observed in animal models, further highlights ligand traps as a promising therapeutic strategy for cancer treatment.

Alliance-focused training.

Alliance-focused training (AFT) aims to increase therapists' ability to recognize, tolerate, and negotiate alliance ruptures by increasing the therapeutic skills of self-awareness, affect regulation, and interpersonal sensitivity. In AFT, therapists are encouraged to draw on these skills when metacommunicating about ruptures with patients. In this article, we present the 3 main supervisory tasks of AFT: videotape analysis of rupture moments, awareness-oriented role-plays, and mindfulness training. We describe the theoretical and empirical support for each supervisory task, provide examples based on actual supervision sessions, and present feedback about the usefulness of the techniques from trainees in our program. We also note some of the challenges involved in conducting AFT and the importance of maintaining a strong supervisory alliance when using this training approach.

Accelerating spirocyclic polyketide synthesis using flow chemistry.

Over the past decade, the integration of synthetic chemistry with flow processing has resulted in a powerful platform for molecular assembly that is making an impact throughout the chemical community. Herein, we demonstrate the extension of these tools to encompass complex natural product synthesis. We have developed a number of novel flow-through processes for reactions commonly encountered in natural product synthesis programs to achieve the first total synthesis of spirodienal A and the preparation of spirangien A methyl ester. Highlights of the synthetic route include an iridium-catalyzed hydrogenation, iterative Roush crotylations, gold-catalyzed spiroketalization and a late-stage cis-selective reduction.

Investigating the impact of alliance-focused training on interpersonal process and therapists' capacity for experiential reflection.

OBJECTIVE: In this article we present preliminary findings from a research program designed to investigate the value of alliance-focused training (AFT), a supervision approach designed to enhance therapists' ability to work constructively with negative therapeutic process. METHOD: In the context of a multiple baseline design, all therapists began treating their patients using cognitive therapy and then joined AFT supervision groups at either session 8 or 16 of a 30 session protocol. Study I investigated the impact of AFT on patient and therapist interpersonal process as assessed through the Structural Analysis of Social Behavior (SASB). Study 2 investigated the impact of AFT on therapists' tendency to reflect on their relationships with their patients in an experientially grounded fashion, as assessed via the Experiencing Scale (EXP). Since one of the goals of AFT is to train therapists to use their own emerging feelings as important clues regarding what may be taking place in the therapeutic relationship, we hypothesized that they would show increased levels of EXP after undergoing AFT. RESULTS AND CONCLUSION: The results of both studies 1 and 2 were for the most part consistent with hypotheses. Implications and future research directions are discussed.

Appraisals of daily romantic relationship experiences in individuals with borderline personality disorder features.

The current study examined the relationship between borderline personality disorder (BPD) features and appraisals of daily romantic relationship experiences. The sample included 114 ethnically diverse, young adult dating couples (total N = 228). Participants completed a 14-day daily diary study and reported negative impact and emotional loss to their romantic partner in response to daily positive and negative self-initiated and partner-initiated romantic experiences. Results indicated that BPD features, even when controlling for relationship satisfaction, total number of relationship experiences, and depressive symptoms, were associated with reporting greater negative impact and greater emotional loss to both partner-initiated negative and positive experiences. BPD features were generally not associated with reporting greater negative impact and emotional loss in response to self-initiated negative and positive experiences. The results suggest that individuals with BPD features have a negative interpretation bias to both negative and positive experiences and the effect is generally specific to partner-initiated experiences. Negative appraisals may be one mechanism underlying interpersonal dysfunction in those with BPD features and interventions that directly assess and target these cognitive biases may help improve individual well-being and overall couple functioning.

The prediction of flanking sound transmission below the critical frequency.

Although reliable methods exist to predict the apparent sound reduction index of heavy, homogeneous isotopic building constructions, these methods are not appropriate for use with lightweight building constructions which typically have critical frequencies in or above the frequency range of interest. Three main methods have been proposed for extending the prediction of flanking sound transmission to frequencies below the critical frequency. The first method is the direct prediction which draws on a database of measurements of the flanking transmission of individual flanking paths. The second method would be a modification of the method in existing standards. This method requires the calculation of the resonant sound transmission factors. However, most of the approaches proposed to calculate the resonant sound transmission factor work only for the case of single leaf homogeneous isotropic building elements and therefore are not readily applicable to complex building elements. The third method is the measurement or prediction of the resonant radiation efficiency and the airborne diffuse field excited radiation efficiency which includes both the resonant and the non-resonant radiation efficiencies. The third method can currently deal with complex building elements if the radiation efficiencies can be measured or predicted. This paper examines these prediction methods.

How many mountains can we mine? Assessing the regional degradation of Central Appalachian rivers by surface coal mining.

Surface coal mining is the dominant form of land cover change in Central Appalachia, yet the extent to which surface coal mine runoff is polluting regional rivers is currently unknown. We mapped surface mining from 1976 to 2005 for a 19,581 km(2) area of southern West Virginia and linked these maps with water quality and biological data for 223 streams. The extent of surface mining within catchments is highly correlated with the ionic strength and sulfate concentrations of receiving streams. Generalized additive models were used to estimate the amount of watershed mining, stream ionic strength, or sulfate concentrations beyond which biological impairment (based on state biocriteria) is likely. We find this threshold is reached once surface coal mines occupy >5.4% of their contributing watershed area, ionic strength exceeds 308 µS cm(-1), or sulfate concentrations exceed 50 mg L(-1). Significant losses of many intolerant macroinvertebrate taxa occur when as little as 2.2% of contributing catchments are mined. As of 2005, 5% of the land area of southern WV was converted to surface mines, 6% of regional streams were buried in valley fills, and 22% of the regional stream network length drained watersheds with >5.4% of their surface area converted to mines.

Quantitative naturalistic methods for detecting change points in psychotherapy research: an illustration with alliance ruptures.

Analysis of change points in psychotherapy process could increase our understanding of mechanisms of change. In particular, naturalistic change point detection methods that identify turning points or breakpoints in time series data could enhance our ability to identify and study alliance ruptures and resolutions. This paper presents four categories of statistical methods for detecting change points in psychotherapy process: criterion-based methods, control chart methods, partitioning methods, and regression methods. Each method's utility for identifying shifts in the alliance is illustrated using a case example from the Beth Israel Psychotherapy Research program. Advantages and disadvantages of the various methods are discussed.

An empirical model for the equivalent translational compliance of steel studs.

The effect of the resilience of the steel studs on the sound insulation of steel stud cavity walls can be modeled as an equivalent translational compliance in simple models for predicting the sound insulation of walls. Recent numerical calculations have shown that this equivalent translational compliance varies with frequency. This paper determines the values of the equivalent translational compliance of steel studs which make a simple sound insulation theory agree best with experimental sound insulation data for 126 steel stud cavity walls with gypsum plaster board on each side of the steel studs and sound absorbing material in the wall cavity. These values are approximately constant as a function of frequency up to 400 Hz. Above 400 Hz they decrease approximately as a non-integer power of the frequency. The equivalent translational compliance also depends on the mass per unit surface area of the cladding on each side of the steel studs and on the width of the steel studs. Above 400 Hz, this compliance also depends on the stud spacing. The best fit approximation is used with a simple sound insulation prediction model to predict the sound insulation of steel stud cavity walls whose sound insulation has been determined experimentally.

Increasing donor-recipient weight mismatch in pediatric orthotopic heart transplantation does not adversely affect outcome.

OBJECTIVE: The aim of the study was to show the effect of heart transplant donor-recipient weight mismatch on mortality, right-ventricular (RV) failure, and medium-term control of systemic blood pressure. METHODS: From 2000 to 2008 inclusive, 161 patients undergoing orthotopic heart transplantation at our unit were retrospectively analyzed. The cohort was divided into three groups of similar size depending on the tertile ranges of the donor-recipient weight ratio. Median follow-up was 4.81 years. Donor-recipient body weight ratio was analyzed with respect to intubation time, time in intensive care unit (ITU), development of RV failure, medium-term survival, and freedom from medium-term hypertension. RESULTS: The median age was 115 months (23 days to 18 years), at a median weight of 26.9 kg (3-88 kg) at transplant. Median donor-recipient weight ratio was 1.61 (0.62-3.25). Mean intubation time was 448 h (SD 749.2), mean time in the ITU 302.7 h (SD 617.8). On linear regression, these were not related to donor-recipient weight ratio. A total of 38 patients (23.6%) developed postoperative RV failure. Nearly one-fifth (18.9) of patients in the lowest tertile group developed RV failure. In the middle tertile group, 24.5% developed RV failure and 28.8% in the upper tertile of weight mismatch, although this was not statistically significant (p = 0.48). On survival analysis, there was a higher mortality among those with the lowest tertile of mismatch (log-rank p = 0.04), but there was no difference in midterm survival on condition of survival to discharge (log-rank p = 0.14). There was also no association between weight ratio and freedom from medium-term hypertension as measured on serial 24-h ambulatory blood pressure monitoring (log-rank p = 0.39). There were nine patients in whom the weight mismatch was 3 or greater. There was no association between this 'extreme' mismatch group and either midterm mortality (p = 0.76) or freedom from hypertension (p = 0.62), but this was associated with the need for postoperative extracorporeal membrane oxygenator (ECMO) support (p < 0.01). CONCLUSIONS: Our current policy involves accepting a maximum donor-recipient weight ratio of 3. These encouraging findings cautiously justify this policy, in an era when marginal donors are increasingly sought.

Manual therapy with and without vestibular rehabilitation for cervicogenic dizziness: a systematic review.

BACKGROUND: Manual therapy is an intervention commonly advocated in the management of dizziness of a suspected cervical origin. Vestibular rehabilitation exercises have been shown to be effective in the treatment of unilateral peripheral vestibular disorders, and have also been suggested in the literature as an adjunct in the treatment of cervicogenic dizziness. The purpose of this systematic review is to evaluate the evidence for manual therapy, in conjunction with or without vestibular rehabilitation, in the management of cervicogenic dizziness. METHODS: A comprehensive search was conducted in the databases Scopus, Mantis, CINHAL and the Cochrane Library for terms related to manual therapy, vestibular rehabilitation and cervicogenic dizziness. Included studies were assessed using the Maastricht-Amsterdam criteria. RESULTS: A total of fifteen articles reporting findings from thirteen unique investigations, including five randomised controlled trials and eight prospective, non-controlled cohort studies were included in this review. The methodological quality of the included studies was generally poor to moderate. All but one study reported improvement in dizziness following either unimodal or multimodal manual therapy interventions. Some studies reported improvements in postural stability, joint positioning, range of motion, muscle tenderness, neck pain and vertebrobasilar artery blood flow velocity. DISCUSSION: Although it has been argued that manual therapy combined with vestibular rehabilitation may be superior in the treatment of cervicogenic dizziness, there are currently no observational and experimental studies demonstrating such effects. A rationale for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is presented. CONCLUSION: There is moderate evidence to support the use of manual therapy, in particular spinal mobilisation and manipulation, for cervicogenic dizziness. The evidence for combining manual therapy and vestibular rehabilitation in the management of cervicogenic dizziness is lacking. Further research to elucidate potential synergistic effects of manual therapy and vestibular rehabilitation is strongly recommended.

Yoga to treat nonspecific low back pain.

Low back pain is common and poses a challenge for clinicians to find effective treatment to prevent it from becoming chronic. Chronic low back pain can have a significant impact on an employee's ability to remain an active and productive member of the work force due to increased absenteeism, duty restrictions, or physical limitations from pain. Low back pain is the most common cause of work-related disability among employees younger than 46 years. Advancing technology and less invasive surgical procedures have not improved outcomes for employees who suffer from low back pain. Most continue to experience some pain and dysfunction after conventional treatments such as injections and surgery. An alternative treatment that could reduce nonspecific chronic low back pain would benefit both employees and employers. Exercising and remaining active are part of most guidelines' routine care recommendations but are not well defined.

Gold mining in the Peruvian Amazon: global prices, deforestation, and mercury imports.

Many factors such as poverty, ineffective institutions and environmental regulations may prevent developing countries from managing how natural resources are extracted to meet a strong market demand. Extraction for some resources has reached such proportions that evidence is measurable from space. We present recent evidence of the global demand for a single commodity and the ecosystem destruction resulting from commodity extraction, recorded by satellites for one of the most biodiverse areas of the world. We find that since 2003, recent mining deforestation in Madre de Dios, Peru is increasing nonlinearly alongside a constant annual rate of increase in international gold price (∼18%/yr). We detect that the new pattern of mining deforestation (1915 ha/year, 2006-2009) is outpacing that of nearby settlement deforestation. We show that gold price is linked with exponential increases in Peruvian national mercury imports over time (R(2) = 0.93, p = 0.04, 2003-2009). Given the past rates of increase we predict that mercury imports may more than double for 2011 (∼500 t/year). Virtually all of Peru's mercury imports are used in artisanal gold mining. Much of the mining increase is unregulated/artisanal in nature, lacking environmental impact analysis or miner education. As a result, large quantities of mercury are being released into the atmosphere, sediments and waterways. Other developing countries endowed with gold deposits are likely experiencing similar environmental destruction in response to recent record high gold prices. The increasing availability of satellite imagery ought to evoke further studies linking economic variables with land use and cover changes on the ground.

Repairing alliance ruptures.

In this article, we review the existing empirical research on the topic of therapeutic alliance ruptures in psychotherapy. Ruptures in the therapeutic alliance are defined as episodes of tension or breakdown in the collaborative relationship between patient and therapist. Two meta-analyses were conducted. The first reviewed studies examining the relation between rupture-repair episodes and treatment outcome (r = .24, z = 3.06, 95% CI [.09, .39], p = .002, k = 3, N = 148). The second meta-analysis reviewed the research examining the impact on treatment outcome of training therapists in the use of alliance rupture intervention principles (prepost r = .65, z = 5.56, 95% CI [.46, .78], p < .001, k = 8, N = 376). Both meta-analyses provided promising evidence regarding the relevance of alliance rupture-repair processes to therapeutic outcome. The limitations of the research reviewed are discussed as well as practice implications for repairing the inevitable alliance ruptures in psychotherapy.

Diastereoselective chain-elongation reactions using microreactors for applications in complex molecule assembly.

Diastereoselective chain-elongation reactions are important transformations for the assembly of complex molecular structures, such as those present in polyketide natural products. Here we report new methods for performing crotylation reactions and homopropargylation reactions by using newly developed low-temperature flow-chemistry technology. In-line purification protocols are described, as well as the application of the crotylation protocol in an automated multi-step sequence.

HTT haplotypes contribute to differences in Huntington disease prevalence between Europe and East Asia.

Huntington disease (HD) results from CAG expansion in the huntingtin (HTT) gene. Although HD occurs worldwide, there are large geographic differences in its prevalence. The prevalence in populations derived from Europe is 10-100 times greater than in East Asia. The European general population chromosomes can be grouped into three major haplogroups (group of similar haplotypes): A, B and C. The majority of HD chromosomes in Europe are found on haplogroup A. However, in the East-Asian populations of China and Japan, we find the majority of HD chromosomes are associated with haplogroup C. The highest risk HD haplotypes (A1 and A2), are absent from the general and HD populations of China and Japan, and therefore provide an explanation for why HD prevalence is low in East Asia. Interestingly, both East-Asian and European populations share a similar low level of HD on haplogroup C. Our data are consistent with the hypothesis that different HTT haplotypes have different mutation rates, and geographic differences in HTT haplotypes explain the difference in HD prevalence. Further, the bias for expansion on haplogroup C in the East-Asian population cannot be explained by a higher average CAG size, as haplogroup C has a lower average CAG size in the general East-Asian population compared with other haplogroups. This finding suggests that CAG-tract size is not the only factor important for CAG instability. Instead, the expansion bias may be because of genetic cis-elements within the haplotype that influence CAG instability in HTT, possibly through different mutational mechanisms for the different haplogroups.

The continuous flow synthesis of butane-2,3-diacetal protected building blocks using microreactors.

The continuous flow synthesis of butane-2,3-diacetal protected derivatives has been achieved using commercially available flow chemistry microreactors in concert with solid supported reagents and scavengers to provide in-line purification systems. The BDA protected products are all obtained in superior yield to the corresponding batch processes.

Clinical consensus strategies for interpersonal problems between young adults and their parents.

OBJECTIVE: Research that identifies areas of agreement among expert therapists can complement findings from clinical trials by highlighting common practices as well as innovations. The present study accessed consensus among expert therapists on the effectiveness of clinical strategies for treating young adults experiencing interpersonal problems with their parents. METHOD: This study drew on the behavioral-analytic model (Goldfried & D'Zurilla, 1969) and the methodology of the Expert Consensus Guideline Series (Frances, Kahn, Carpenter, Ross, & Docherty, 1996). In Phase I, 54 therapists (mean age = 60.32 years; 55.6% women, 44.4% men; 96.3% White/European American) provided clinical situations involving young adult clients and their parents. In Phase II, 171 therapists (mean age = 59.45 years; 47.4% women, 52.0% men; 91.8% White/European American) proposed responses to the situations, and more general clinical strategies underlying the responses were identified. In Phase III, 134 peer-nominated expert therapists (a mean of 22.33 therapists per situation; mean age = 55.46 years; 61.2% women, 34.3% men; 91.0% White/European American) rated the effectiveness of these clinical strategies. RESULTS: Results indicated that the experts reached consensus on strategies rated as highly effective; in particular, they agreed on the value of exploring clients' emotional experience and providing validation. Participants reached greater agreement on strategies for use in future sessions than strategies for immediate use. Exploratory analyses revealed correlations between experts' theoretical orientations and their ratings. CONCLUSIONS: The findings provide converging evidence of the value of exploring emotions and validating clients and, further, demonstrate the feasibility of this method for accessing clinicians' experience.

Acute right ventricular failure after pediatric cardiac transplant: predictors and long-term outcome in current era of transplantation medicine.

OBJECTIVES: To identify pretransplant factors associated with postprocedural right ventricular failure and the relationship between right ventricular failure and long-term survival in children. METHODS: Records were reviewed for children having heart transplantation from 2000 to 2006. RESULTS: Right ventricular failure was identified by clinical and echocardiographic parameters in 33/129 (25%) recipients: dilated cardiomyopathy in 14/90 (15%), congenital heart disease in 11/27 (41%), and restrictive cardiomyopathy in 8/12 (66%). In 9 of 12 (75%), known elevated (reactive) pulmonary vascular resistance progressed to right ventricular failure. In a further 23/117 (20%) recipients, pulmonary vascular resistance within predefined acceptable range progressed to right ventricular failure. Multiple logistic regression analyses indicated elevated pulmonary vascular resistance (odds ratio 12.30; 95% confidence interval 2.73, 55.32; P = .001) and primary diagnosis, restrictive cardiomyopathy (odds ratio 9.21; 95% confidence interval 2.07, 41.12; P = .004), and congenital heart disease (odds ratio 4.07; 95% confidence interval 1.36, 12.19; P = .012) were strongly associated with right ventricular failure, but duration of heart failure, pretransplant mechanical support, donor status, and ischemic times were not. Treatment included inhaled nitric oxide in 28 (84%), mechanical support in 10 (31%), hemofiltration in 13 (40%), and retransplantation in 2. A Cox multiple regression model including: primary diagnosis, right ventricular failure, and elevated pulmonary vascular resistance indicated that only the latter was independently linked with eventual mortality (hazards ratio 5.45; 95% confidence interval 1.36, 21.96; P = .017). CONCLUSIONS: Primary diagnosis and pretransplant elevated reactive pulmonary vascular resistance are both linked to the evolution of right ventricular failure. Pulmonary vascular resistance assessment in end-stage heart failure is challenging; therefore, avoidance of right ventricular failure may not always be possible. Aggressive early treatment may mitigate the effects of right ventricular failure: pretransplant elevated pulmonary vascular resistance was independently associated with long-term survival, but right ventricular failure was not.