Inverse metal-assisted chemical etching of germanium with gold and hydrogen peroxide.

Metal-assisted chemical etching (MACE) is a flexible technique for texturing the surface of semiconductors. In this work, we study the spatial variation of the etch profile, the effect of angular orientation relative to the crystallographic planes, and the effect of doping type. We employ gold in direct contact with germanium as the metal catalyst, and dilute hydrogen peroxide solution as the chemical etchant. With this catalyst-etchant combination, we observe inverse-MACE, where the area directly under gold is not etched, but the neighboring, exposed germanium experiences enhanced etching. This enhancement in etching decays exponentially with the lateral distance from the gold structure. An empirical formula for the gold-enhanced etching depth as a function of lateral distance from the edge of the gold film is extracted from the experimentally measured etch profiles. The lateral range of enhanced etching is approximately 10-20µm and is independent of etchant concentration. At length scales beyond a few microns, the etching enhancement is independent of the orientation with respect to the germanium crystallographic planes. The etch rate as a function of etchant concentration follows a power law with exponent smaller than 1. The observed etch rates and profiles are independent of whether the germanium substrate is n-type, p-type, or nearly intrinsic.

Community capacity coach: Embedded support to implement evidenced-based prevention.

Given the pervasive nature of child abuse and neglect, multilevel public health approaches are necessary. Implementation science can help in understanding the most effective ways to build infrastructure and support delivery of such approaches. In this theoretical paper, we describe the implementation of the Positive Parenting Program (Triple P), an evidence-based population-level parenting program in South Carolina. While implementation science has informed how to move population-level efforts to scale, we discuss challenges that persist in practice, such as when there is a need for multiple stakeholders to understand, support, and apply implementation best practices in a systematic and consistent way. To address this challenge, we introduce the role of a Community Capacity Coach, who lives in the local community and works towards the implementation of Triple P. The Coach is responsible for bridging gaps between the local community and statewide support systems. We detail the ways in which the Coach's role aligns with key intermediary functions, and how the Coach is embedded within the larger Triple P statewide support system. We then discuss the assessment of the Coach's impact; and conclude with future directions and next steps for this role within Triple P South Carolina.

MARCKS regulates neuritogenesis and interacts with a CDC42 signaling network.

Through the process of neuronal differentiation, newly born neurons change from simple, spherical cells to complex, sprawling cells with many highly branched processes. One of the first stages in this process is neurite initiation, wherein cytoskeletal modifications facilitate membrane protrusion and extension from the cell body. Hundreds of actin modulators and microtubule-binding proteins are known to be involved in this process, but relatively little is known about how upstream regulators bring these complex networks together at discrete locations to produce neurites. Here, we show that Myristoylated alanine-rich C kinase substrate (MARCKS) participates in this process. Marcks-/- cortical neurons extend fewer neurites and have less complex neurite arborization patterns. We use an in vitro proteomics screen to identify MARCKS interactors in developing neurites and characterize an interaction between MARCKS and a CDC42-centered network. While the presence of MARCKS does not affect whole brain levels of activated or total CDC42, we propose that MARCKS is uniquely positioned to regulate CDC42 localization and interactions within specialized cellular compartments, such as nascent neurites.

MARCKS Is Necessary for Netrin-DCC Signaling and Corpus Callosum Formation.

Axons of the corpus callosum (CC), the white matter tract that connects the left and right hemispheres of the brain, receive instruction from a number of chemoattractant and chemorepulsant cues during their initial navigation towards and across the midline. While it has long been known that the CC is malformed in the absence of Myristoylated alanine-rich C-kinase substrate (MARCKS), evidence for a direct role of MARCKS in axon navigation has been lacking. Here, we show that MARCKS is necessary for Netrin-1 (NTN1) signaling through the DCC receptor, which is critical for axon guidance decisions. Marcks null (Marcks-/-) neurons fail to respond to exogenous NTN1 and are deficient in markers of DCC activation. Without MARCKS, the subcellular distributions of two critical mediators of NTN1-DCC signaling, the tyrosine kinases PTK2 and SRC, are disrupted. Together, this work establishes a novel role for MARCKS in axon dynamics and highlights the necessity of MARCKS as an organizer of DCC signaling at the membrane.

The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer.

Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations. In particular, the existence of autocrine, ligand-dependent Hh signaling in SCLC has been disputed. In a conditional Tp53;Rb1 mutant mouse model of SCLC, we now demonstrate a requirement for the Hh ligand Sonic Hedgehog (Shh) for the progression of SCLC. Conversely, we show that conditional Shh overexpression activates canonical Hh signaling in SCLC cells, and markedly accelerates tumor progression. When compared to mouse SCLC tumors expressing an activating, ligand-independent Smo mutant, tumors overexpressing Shh exhibited marked chromosomal instability and Smoothened-independent upregulation of Cyclin B1, a putative non-canonical arm of the Hh pathway. In turn, we show that overexpression of Cyclin B1 induces chromosomal instability in mouse embryonic fibroblasts lacking both Tp53 and Rb1. These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability.

Mitochondrial DNA plasticity is an essential inducer of tumorigenesis.

Although mitochondrial DNA has been implicated in diseases such as cancer, its role remains to be defined. Using three models of tumorigenesis, namely glioblastoma multiforme, multiple myeloma and osteosarcoma, we show that mitochondrial DNA plays defining roles at early and late tumour progression. Specifically, tumour cells partially or completely depleted of mitochondrial DNA either restored their mitochondrial DNA content or actively recruited mitochondrial DNA, which affected the rate of tumorigenesis. Nevertheless, non-depleted tumour cells modulated mitochondrial DNA copy number at early and late progression in a mitochondrial DNA genotype-specific manner. In glioblastoma multiforme and osteosarcoma, this was coupled with loss and gain of mitochondrial DNA variants. Changes in mitochondrial DNA genotype affected tumour morphology and gene expression patterns at early and late progression. Importantly, this identified a subset of genes that are essential to early progression. Consequently, mitochondrial DNA and commonly expressed early tumour-specific genes provide novel targets against tumorigenesis.

Therapeutic effect of flax-based diets on fatty liver in aged laying hens.

This study examined the ability of flax-based ingredients to attenuate nonalcoholic fatty liver disease ( NAFLD: ) in aged laying hens-a novel and more physiologically relevant model of human disease. Our results showed only hens supplemented with whole flaxseed ( WFX: ) reduced steatosis and hepatocellular ballooning. Serum AST was also reduced in hens provided WFX and defatted flaxseed meal ( DFM: ). Hepatic ω-3 PUFA enrichment was improved with supplementation of WFX, DFM, and flaxseed oil ( FXO: ). However, this effect was more evident in the WFX group. In contrast, transcript abundance of genes linked to NAFLD were predominantly modified with FXO supplementation. Taken together, our data indicate a potential synergistic relationship between the fatty acid and lignan content in flaxseed which attenuated the progression of NAFLD in aged laying hens. Although more research is necessary, these findings demonstrate the potential use of whole flaxseed for the treatment and prevention of NAFLD in humans.

World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer

"BACKGROUND: It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. METHODS: Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. RESULTS: There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. CONCLUSION: Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries."

Dilated perivascular spaces in the Basal Ganglia are a biomarker of small-vessel disease in a very elderly population with dementia.

BACKGROUND AND PURPOSE: Dilated perivascular spaces have been shown to be a specific biomarker of cerebral small-vessel disease in young patients with dementia. Our aim was to examine the discriminative power of dilated cerebral perivascular spaces as biomarkers of small-vessel disease in a very elderly population of patients with dementia. MATERIALS AND METHODS: We studied healthy volunteers (n = 65; mean age, 78 ± 5.6 years) and subjects with vascular dementia (n = 39; mean age, 76.9 ± 7.7 years) and Alzheimer disease (n = 47; mean age, 74.1 ± 8.5 years). We compared white matter hyperintensity and 2 semiquantitative perivascular space scoring systems (perivascular space-1 and perivascular space-2). Intra- and interobserver agreement was assessed by using a weighted Cohen κ statistic. Multinomial regression modeling was used to assess the discriminative power of imaging features to distinguish clinical groups. RESULTS: White matter hyperintensity scores were higher in vascular dementia than in Alzheimer disease (P < .05) or healthy volunteers (P < .01). The perivascular space-1 score was higher in vascular dementia and Alzheimer disease than in healthy volunteers (P < .01). The perivascular space-2 score in the centrum semiovale showed no intergroup differences. However, perivascular space-2 in the basal ganglia was higher in vascular dementia than in Alzheimer disease (P < .05) or healthy volunteers (P < .001) and higher in Alzheimer disease than in healthy volunteers (P < .001). Modeling of dementia versus healthy volunteers, Alzheimer disease versus healthy volunteers, and vascular dementia against Alzheimer disease demonstrated perivascular space-2basal ganglia as the only imaging parameter with independent significant discriminative power (P < .01, P < .01, and P < .05) with areas under the receiver operating characteristic curve of 0.855, 0.774, and 0.71, respectively. Modeling of vascular dementia versus healthy volunteers showed that perivascular space-2basal ganglia (P < .01) and the modified Scheltens score (P < .05) contributed significant, independent discriminatory power, accounting for 34% and 13% of the variance in the model respectively. CONCLUSIONS: Dilated perivascular spaces remain a valuable biomarker of small-vessel disease in an elderly population.

Soy protein isolate modified metabolic phenotype and hepatic Wnt signaling in obese Zucker rats.

We have previously shown that soy protein isolate (SPI) with intact phytoestrogen content prevented obesity-related dysfunction. Recent data have suggested that soy ingredients may act as regulators of adipogenic programming in adipose tissue (AT) and liver. Thus, the current study was undertaken to determine whether the beneficial effects of SPI are linked to changes in adipogenic regulators, such as the Wnt signaling cascade. For this, lean (LZR) and obese Zucker (OZR) rats were provided isocaloric and isonitrogenous diets containing SPI, sodium caseinate, or dairy whey protein for 17 weeks. At termination, SPI increased body weight and total adiposity in rodents, which corresponded with an increase in both adipocyte size and number. Furthermore, markers of inflammation, hypercholesterolemia, and hepatic steatosis were all reduced in OZR rats provided SPI. Transcript abundance of several canonical and noncanonical Wnt signaling intermediates in liver, but not AT, was distinctly modified by SPI. Collectively, these data confirm the protective SPI attenuated obesity-related metabolic dysfunction conceivably through regulation of adipogenic programming, as evident by changes in AT morphology and hepatic Wnt signaling. Collectively, this study confirmed the potential utilization of soy protein and its bioactive ingredients for prevention and treatment of obesity-related comorbidities.

Internal structure, hygroscopic and reactive properties of mixed sodium methanesulfonate-sodium chloride particles.

Internal structures, hygroscopic properties and heterogeneous reactivity of mixed CH(3)SO(3)Na/NaCl particles were investigated using a combination of computer modeling and experimental approaches. Surfactant properties of CH(3)SO(3)(-) ions and their surface accumulation in wet, deliquesced particles were assessed using molecular dynamics (MD) simulations and surface tension measurements. Internal structures of dry CH(3)SO(3)Na/NaCl particles were investigated using scanning electron microscopy (SEM) assisted with X-ray microanalysis mapping, and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The combination of these techniques shows that dry CH(3)SO(3)Na/NaCl particles are composed of a NaCl core surrounded by a CH(3)SO(3)Na shell. Hygroscopic growth, deliquescence and efflorescence phase transitions of mixed CH(3)SO(3)Na/NaCl particles were determined and compared to those of pure NaCl particles. These results indicate that particles undergo a two step deliquescence transition: first at ∼69% relative humidity (RH) the CH(3)SO(3)Na shell takes up water, and then at ∼75% RH the NaCl core deliquesces. Reactive uptake coefficients for the particle-HNO(3) heterogeneous reaction were determined at different CH(3)SO(3)Na/NaCl mixing ratios and RH. The net reaction probability decreased notably with increasing CH(3)SO(3)Na and at lower RH.

Implementation of liquid culture for tuberculosis diagnosis in a remote setting: lessons learned.

Although sputum smear microscopy is the primary method for tuberculosis (TB) diagnosis in low-resource settings, it has low sensitivity. The World Health Organization recommends the use of liquid culture techniques for TB diagnosis and drug susceptibility testing in low- and middle-income countries. An evaluation of samples from southern Sudan found that culture was able to detect cases of active pulmonary TB and extra-pulmonary TB missed by conventional smear microscopy. However, the long delays involved in obtaining culture results meant that they were usually not clinically useful, and high rates of non-tuberculous mycobacteria isolation made interpretation of results difficult. Improvements in diagnostic capacity and rapid speciation facilities, either on-site or through a local reference laboratory, are crucial.

Acute hemodynamic changes after rapid intravenous bolus dosing of dexmedetomidine in pediatric heart transplant patients undergoing routine cardiac catheterization.

BACKGROUND: Dexmedetomidine is a highly selective α(2)-adrenoceptor agonist with sedative, anxiolytic, and analgesic properties that has minimal effects on respiratory drive. Its sedative and hypotensive effects are mediated via central α(2A) and imidazoline type 1 receptors while activation of peripheral α(2B)-adrenoceptors result in an increase in arterial blood pressure and systemic vascular resistance. In this randomized, prospective, clinical study, we attempted to quantify the short-term hemodynamic effects resulting from a rapid i.v. bolus administration of dexmedetomidine in pediatric cardiac transplant patients. METHODS: Twelve patients, aged 10 years or younger, weighing ≤40 kg, presenting for routine surveillance of right and left heart cardiac catheterization after cardiac transplantation were enrolled. After an inhaled or i.v. induction, the tracheas were intubated and anesthesia was maintained with 1 minimum alveolar concentration of isoflurane in room air, fentanyl (1 µg/kg), and rocuronium (1 mg/kg). At the completion of the planned cardiac catheterization, 100% oxygen was administered. After recording a set of baseline values that included heart rate (HR), systolic blood pressure, diastolic blood pressure, central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and thermodilution-based cardiac output, a rapid i.v. dexmedetomidine bolus of either 0.25 or 0.5 µg/kg was administered over 5 seconds. The hemodynamic measurements were repeated at 1 minute and 5 minutes. RESULTS: There were 6 patients in each group. Investigation suggested that systolic blood pressure, diastolic blood pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance all increased at 1 minute after rapid i.v. bolus for both doses and decreased significantly to near baseline for both doses by 5 minutes. The transient increase in pressures was more pronounced in the systemic system than in the pulmonary system. In the systemic system, there was a larger percent increase in the diastolic pressures than the systolic pressures. Cardiac output, central venous pressure, and pulmonary vascular resistance did not change significantly. HR decreased at 1 minute for both doses and was, within the 0.5 µg/kg group, the only hemodynamic variable still changed from baseline at the 5-minute time point. CONCLUSION: Rapid i.v. bolus administration of dexmedetomidine in this small sample of children having undergone heart transplants was clinically well tolerated, although it resulted in a transient but significant increase in systemic and pulmonary pressure and a decrease in HR. In the systemic system, there is a larger percent increase in the diastolic pressures than the systolic pressures and, furthermore, these transient increases in pressures were more pronounced in the systemic system than in the pulmonary system.

Barriers to human immunodeficiency virus testing of tuberculosis patients in Thailand, 2004-2007.

SETTING: Tuberculosis (TB) clinics in five provinces and one national referral hospital in Thailand. OBJECTIVE: To identify risk factors for TB patients not receiving human immunodeficiency virus (HIV) pre-test counseling and testing in Thailand. DESIGN: We collected data on TB patients treated at participating facilities from 2004 to 2007. Patients with known HIV status at the time of TB diagnosis were excluded from the analysis. We performed multivariate logistic regression to determine patient and facility characteristics associated with HIV counseling and testing. RESULTS: Of 15 903 TB patients, HIV pre-test counseling was provided to 13 604 (86%). HIV testing was provided to 11 702 (86%) of those counseled. Of 6141 patients with unknown HIV status, 2323 (38%) were treated in facilities that provide HIV testing in TB clinics compared with 6412 (58%) of 11 003 non-HIV-infected and 3814 (62%) of 6121 HIV-infected patients (P < 0.05). In multivariate analysis, patients treated in facilities in which HIV testing of TB patients was performed somewhere other than the TB clinic were significantly less likely to undergo HIV pre-test counseling (adjusted OR 1.55, 95%CI 1.28-1.86). CONCLUSION: In Thailand, providing HIV testing directly in TB clinics, rather than in other settings, may increase the proportion of TB patients with known HIV status.

Diagnosing metal fume fever--an integrated approach.

BACKGROUND: Exposure to high concentrations of zinc oxide fume can cause metal fume fever (MFF). Two cases occurring following the oxy-acetylene cutting of galvanized steel frames are reported. AIMS: To show that integrated working is valuable as secondary health care staff may not be familiar with MFF. METHODS: Site visits by Her Majesty's Medical, Health and Safety (H&S) and Specialist Occupational Hygiene Inspectors to gather information and cooperation with occupational health, primary and secondary health care staff to diagnose MFF. RESULTS: Poor exposure control caused metal fume inhalation in these cases. Multidisciplinary working established diagnosis, causation and compliance with H&S legislation. CONCLUSIONS: Risk assessments are required to identify health risks and to determine required exposure control measures. Failure to do this resulted in an unusual case of MFF leading to hospital admission. Diagnosis can be delayed if a full occupational history is not taken. Successful investigation of such cases benefits from collaborative working.

A survey of occupational exposure to 4,4'-methylene-bis (2-chloroaniline) (MbOCA) in the UK.

OBJECTIVES: The main objective of the study was to gather information about the current controls and levels of exposure to 4,4'-methylene-bis (2-chloroaniline) (MbOCA) in a representative cross section of workplaces that use it to manufacture polyurethane elastomers. The study also aimed to investigate whether controls and guidance could be improved and to investigate exposure to isocyanates in these workplaces using biological monitoring. METHODS: An occupational hygienist and a field scientist visited the two UK suppliers and 20 out of the 25 workplaces known to be using MbOCA in the UK during 2005 and 2006. They collected air samples, surface wipes, gloves, and urine samples and made observations to assess exposure and the adequacy of controls. All samples were analysed for MbOCA and urine samples were additionally analysed for isocyanate metabolites. A statistical analysis was made of the results. RESULTS: Only 2.5% of the 80 personal inhalation exposures to MbOCA exceeded the workplace exposure limit of 5 microg m(-3) 8-h time-weighted average and 84% were below the limit of detection (LOD). Surface samples (n = 334) were collected from MbOCA users and suppliers and 60% had detectable levels of MbOCA ranging from 0.019 to 400 microg cm(-2). The highest levels were around a hopper, ovens, and the weighing and pouring areas. MbOCA was also detected in 8 of the 75 samples collected from areas not likely to be in contact with MbOCA. At the two suppliers, samples (n = 28) were collected from the outside surfaces of recently imported kegs, pallets, and the floor around kegs. Six samples had detectable levels and four of these (0.2, 0.8, 1, and 6 microg cm(-2)) were from the floor and pallets in both suppliers. The other two positive results were found on the outside rim (18 microg cm(-2)) and side (23 microg cm(-2)) of a keg at one supplier indicating contamination by the manufacturer. Urine samples (n = 79) were collected and 49% were below the LOD for MbOCA and only three samples had levels of MbOCA that exceeded the biological monitoring guidance value (BMGV) of 15 micromol mol(-1) creatinine. The highest urinary MbOCA concentrations were in samples from workers casting and moulding. The 90th percentile of the urine MbOCA results was 8.6 micromol MbOCA per mol creatinine. Urine samples were also analysed for the diamine metabolites of toluene diisocyanate and hexamethylene diisocyanate and 33% had detectable levels with 22 and 13% of results, respectively, above the BMGV for isocyanates (1 micromol isocyanate-derived diamine per mol creatinine). The maximum urinary concentration of toluene diamine and hexane diamine were 15.6 and 10.1 micromol mol(-1) creatinine, respectively. CONCLUSIONS: The survey found that the measures used to control exposure to MbOCA could be improved. Although air levels of MbOCA were generally low, there was evidence of spread of surface contamination and poor maintenance of controls such as local exhaust ventilation. A BMGV based on the 90th percentile of data from workplaces with good control would be less than the 90% value of 8.6 micromol mol(-1) creatinine found in this study and suggests that the current BMGV of 15 micromol mol(-1) creatinine is no longer acting as a stimulus to reduce exposure. The metabolites of isocyanates found in urine samples in this study could arise from inhalation exposure to isocyanates or from dermal exposure to either isocyanates or their diamine breakdown product and need further investigation.

Complex temporal patterns of spontaneous initiation and termination of reentry in a loop of cardiac tissue.

A two-component model is developed consisting of a discrete loop of cardiac cells that circulates action potentials as well as a pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and the pacer's action are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability (T-bistability) of reentrant circulation and in some cases, also phase-resetting interactions with the pacer.