ISPCAN child abuse screening tool children's version (ICAST-C): Instrument development and multi-national pilot testing

Objective To develop a child victimization survey among a diverse group of child protection experts and examine the performance of the instrument through a set of international pilot studies. Methods The initial draft of the instrument was developed after input from scientists and practitioners representing 40 countries. Volunteers from the larger group of scientists participating in the Delphi review of the ICAST P and R reviewed the ICAST C by email in 2 rounds resulting in a final instrument. The ICAST C was then translated and back translated into six languages and field tested in four countries using a convenience sample of 571 children 12–17 years of age selected from schools and classrooms to which the investigators had easy access. Results The final ICAST C Home has 38 items and the ICAST C Institution has 44 items. These items serve as screeners and positive endorsements are followed by queries for frequency and perpetrator. Half of respondents were boys (49%). Endorsement for various forms of victimization ranged from 0 to 51%. Many children report violence exposure (51%), physical victimization (55%), psychological victimization (66%), sexual victimization (18%), and neglect in their homes (37%) in the last year. High rates of physical victimization (57%), psychological victimization (59%), and sexual victimization (22%) were also reported in schools in the last year. Internal consistency was moderate to high (alpha between .685 and .855) and missing data low (less than 1.5% for all but one item). Conclusions In pilot testing, the ICAST C identifies high rates of child victimization in all domains. Rates of missing data are low, and internal consistency is moderate to high. Pilot testing demonstrated the feasibility of using child self-report as one strategy to assess child victimization. Practice implications The ICAST C is a multi-national, multi-lingual, consensus-based survey instrument. It is available in six languages for international research to estimate child victimization. Assessing the prevalence of child victimization is critical in understanding the scope of the problem, setting national and local priorities, and garnering support for program and policy development aimed at child protection.

Design and flight testing of an integrated solar powered UAV and WSN for greenhouse gas monitoring emissions in agricultural farms

There is an increased interest in measuring the amount of greenhouse gases produced by farming practices . This paper describes an integrated solar powered Unmanned Air Vehicles (UAV) and Wireless Sensor Network (WSN) gas sensing system for greenhouse gas emissions in agricultural lands. The system uses a generic gas sensing system for CH4 and CO2 concentrations using metal oxide (MoX) and non-dispersive infrared sensors, and a new solar cell encapsulation method to power the unmanned aerial system (UAS)as well as a data management platform to store, analyze and share the information with operators and external users. The system was successfully field tested at ground and low altitudes, collecting, storing and transmitting data in real time to a central node for analysis and 3D mapping. The system can be used in a wide range of outdoor applications at a relatively low operational cost. In particular, agricultural environments are increasingly subject to emissions mitigation policies. Accurate measurements of CH4 and CO2 with its temporal and spatial variability can provide farm managers key information to plan agricultural practices. A video of the bench and flight test performed can be seen in the following link: https://www.youtube.com/watch?v=Bwas7stYIxQ

Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6

In humans, congenital spinal defects occur with an incidence of 0.5-1 per 1000 live births. One of the most severe syndromes with such defects is spondylocostal dysostosis (SCD). Over the past decade, the genetic basis of several forms of autosomal recessive SCD cases has been solved with the identification of four causative genes (DLL3, MESP2, LFNG and HES7). Autosomal dominant forms of SCD have also been reported, but to date no genetic etiology has been described for these. Here, we have used exome capture and next-generation sequencing to identify a stoploss mutation in TBX6 that segregates with disease in two generations of one family. We show that this mutation has a deleterious effect on the transcriptional activation activity of the TBX6 protein, likely due to haploinsufficiency. In mouse, Tbx6 is essential for the patterning of the vertebral precursor tissues, somites; thus, mutation of TBX6 is likely to be causative of SCD in this family. This is the first identification of the genetic cause of an autosomal dominant form of SCD, and also demonstrates the potential of exome sequencing to identify genetic causes of dominant diseases even in small families with few affected individuals.

Novel ANKH amino terminus mutation (Pro5Ser) associated with early-onset calcium pyrophosphate disease with associated phosphaturia

This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father.

A mouse model for spondyloepiphyseal dysplasia congenita with secondary osteoarthritis due to a Col2a1 mutation

Progeny of mice treated with the mutagen N-ethyl-N-nitrosourea (ENU) revealed a mouse, designated Longpockets (Lpk), with short humeri, abnormal vertebrae, and disorganized growth plates, features consistent with spondyloepiphyseal dysplasia congenita (SEDC). The Lpk phenotype was inherited as an autosomal dominant trait. Lpk/+ mice were viable and fertile and Lpk/Lpk mice died perinatally. Lpk was mapped to chromosome 15 and mutational analysis of likely candidates from the interval revealed a Col2a1 missense Ser1386Pro mutation. Transient transfection of wild-type and Ser1386Pro mutant Col2a1 c-Myc constructs in COS-7 cells and CH8 chondrocytes demonstrated abnormal processing and endoplasmic reticulum retention of the mutant protein. Histology revealed growth plate disorganization in 14-day-old Lpk/+ mice and embryonic cartilage from Lpk/+ and Lpk/Lpk mice had reduced safranin-O and type-II collagen staining in the extracellular matrix. The wild-type and Lpk/+ embryos had vertical columns of proliferating chondrocytes, whereas those in Lpk/Lpk mice were perpendicular to the direction of bone growth. Electron microscopy of cartilage from 18.5 dpc wild-type, Lpk/+, and Lpk/Lpk embryos revealed fewer and less elaborate collagen fibrils in the mutants, with enlarged vacuoles in the endoplasmic reticulum that contained amorphous inclusions. Micro-computed tomography (CT) scans of 12-week-old Lpk/+ mice revealed them to have decreased bone mineral density, and total bone volume, with erosions and osteophytes at the joints. Thus, an ENU mouse model with a Ser1386Pro mutation of the Col2a1 C-propeptide domain that results in abnormal collagen processing and phenotypic features consistent with SEDC and secondary osteoarthritis has been established.

A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G→A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.

Mutation of perinatal myosin heavy chain

Veugelers et al. (July 29 issue)1 report on patients with the trismus–pseudocamptodactyly syndrome as having a “Carney complex variant.” Among more than 500 patients with the Carney complex in our database, there are none with the trismus–pseudocamptodactyly syndrome.2,3...

The cross-talk of LDL-cholesterol with cell migration: Insights from the Niemann Pick Type C1 mutation

Cholesterol is considered indispensible for the recruitment and functioning of integrins in focal adhesions for cell migration. However, the physiological cholesterol pools that control integrin trafficking and focal adhesion assembly remain unclear. Using Niemann Pick Type C1 (NPC) mutant cells, which accumulate Low Density lipoprotein (LDL)-derived cholesterol in late endosomes (LE), several recent studies indicate that LDL-cholesterol has multiple roles in regulating focal adhesion dynamics. Firstly, targeting of endocytosed LDL-cholesterol from LE to focal adhesions controls their formation at the leading edge of migrating cells. Other newly emerging literature suggests that this may be coupled to vesicular transport of integrins, Src kinase and metalloproteases from the LE compartment to focal adhesions. Secondly, our recent work identified LDL-cholesterol as a key factor that determines the distribution and ability of several Soluble NSF Attachment Protein (SNAP) Receptor (SNARE) proteins, key players in vesicle transport, to control integrin trafficking to the cell surface and extracellular matrix (ECM) secretion. Collectively, dietary, genetic and pathological changes in cholesterol metabolism may link with efficiency and speed of integrin and ECM cell surface delivery in metastatic cancer cells. This commentary will summarize how direct and indirect pathways enable LDL-cholesterol to modulate cell motility.

Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line

This study aimed to investigate the effects of arsenic trioxide (As2O3) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 μmol/L As2O3in vitro, and the primary APL cells were treated with 2.0 μmol/L As2O3in vitro and 0.16 mg kg-1 d-1 As2O3in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use, but the mutation spots were remarkably increased after As2O3 treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: rNB4-As2O3=0.973818, and rAPL-As2O3=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.

Initial prototype testing of Ray's Night Out: A new mobile app targeting risky drinking in young people

Background Risky single occasion drinking (RSOD; 4 or more drinks in <6 h) more than doubles the risk of injury in young people (15 - 25 years). The potential role of smartphone apps in reducing RSOD in young people is yet to be explored. Objective: To describe the initial prototype testing of ‘Ray's Night Out’, a new iPhone app targeting RSOD in young people. Method Quantitative and qualitative methods were used to evaluate the quality, perceived utility, and acceptability of the app among nine young people (19e23 years). Results Participants reported Ray's Night Out had good to excellent levels of functionality and visual appeal, acceptable to good levels of entertainment, interest and information, and acceptable levels of customization and interactivity. Young people thought the app had high levels of youth appeal, would prompt users to think about their alcohol use limits, but was unlikely to motivate a change in alcohol use in its current form. Qualitative data provided several suggestions for improving the app. Conclusion Following revision, Ray's Night Out could provide an effective intervention for RSOD in non help-seeking young people. A randomized controlled trial is currently underway to test the final prototype of the app.

Novel Mass Spectrometric Analysis Methods for Anabolic Androgenic Steroids in Sports Drug Testing

The feasibility of different modern analytical techniques for the mass spectrometric detection of anabolic androgenic steroids (AAS) in human urine was examined in order to enhance the prevalent analytics and to find reasonable strategies for effective sports drug testing. A comparative study of the sensitivity and specificity between gas chromatography (GC) combined with low (LRMS) and high resolution mass spectrometry (HRMS) in screening of AAS was carried out with four metabolites of methandienone. Measurements were done in selected ion monitoring mode with HRMS using a mass resolution of 5000. With HRMS the detection limits were considerably lower than with LRMS, enabling detection of steroids at low 0.2-0.5 ng/ml levels. However, also with HRMS, the biological background hampered the detection of some steroids. The applicability of liquid-phase microextraction (LPME) was studied with metabolites of fluoxymesterone, 4-chlorodehydromethyltestosterone, stanozolol and danazol. Factors affecting the extraction process were studied and a novel LPME method with in-fiber silylation was developed and validated for GC/MS analysis of the danazol metabolite. The method allowed precise, selective and sensitive analysis of the metabolite and enabled simultaneous filtration, extraction, enrichment and derivatization of the analyte from urine without any other steps in sample preparation. Liquid chromatographic/tandem mass spectrometric (LC/MS/MS) methods utilizing electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) were developed and applied for detection of oxandrolone and metabolites of stanozolol and 4-chlorodehydromethyltestosterone in urine. All methods exhibited high sensitivity and specificity. ESI showed, however, the best applicability, and a LC/ESI-MS/MS method for routine screening of nine 17-alkyl-substituted AAS was thus developed enabling fast and precise measurement of all analytes with detection limits below 2 ng/ml. The potential of chemometrics to resolve complex GC/MS data was demonstrated with samples prepared for AAS screening. Acquired full scan spectral data (m/z 40-700) were processed by the OSCAR algorithm (Optimization by Stepwise Constraints of Alternating Regression). The deconvolution process was able to dig out from a GC/MS run more than the double number of components as compared with the number of visible chromatographic peaks. Severely overlapping components, as well as components hidden in the chromatographic background could be isolated successfully. All studied techniques proved to be useful analytical tools to improve detection of AAS in urine. Superiority of different procedures is, however, compound-dependent and different techniques complement each other.

From Polymorph Screening to Dissolution Testing - Solid Phase Analysis during Pharmaceutical Development and Manufacturing

Solid materials can exist in different physical structures without a change in chemical composition. This phenomenon, known as polymorphism, has several implications on pharmaceutical development and manufacturing. Various solid forms of a drug can possess different physical and chemical properties, which may affect processing characteristics and stability, as well as the performance of a drug in the human body. Therefore, knowledge and control of the solid forms is fundamental to maintain safety and high quality of pharmaceuticals. During manufacture, harsh conditions can give rise to unexpected solid phase transformations and therefore change the behavior of the drug. Traditionally, pharmaceutical production has relied on time-consuming off-line analysis of production batches and finished products. This has led to poor understanding of processes and drug products. Therefore, new powerful methods that enable real time monitoring of pharmaceuticals during manufacturing processes are greatly needed. The aim of this thesis was to apply spectroscopic techniques to solid phase analysis within different stages of drug development and manufacturing, and thus, provide a molecular level insight into the behavior of active pharmaceutical ingredients (APIs) during processing. Applications to polymorph screening and different unit operations were developed and studied. A new approach to dissolution testing, which involves simultaneous measurement of drug concentration in the dissolution medium and in-situ solid phase analysis of the dissolving sample, was introduced and studied. Solid phase analysis was successfully performed during different stages, enabling a molecular level insight into the occurring phenomena. Near-infrared (NIR) spectroscopy was utilized in screening of polymorphs and processing-induced transformations (PITs). Polymorph screening was also studied with NIR and Raman spectroscopy in tandem. Quantitative solid phase analysis during fluidized bed drying was performed with in-line NIR and Raman spectroscopy and partial least squares (PLS) regression, and different dehydration mechanisms were studied using in-situ spectroscopy and partial least squares discriminant analysis (PLS-DA). In-situ solid phase analysis with Raman spectroscopy during dissolution testing enabled analysis of dissolution as a whole, and provided a scientific explanation for changes in the dissolution rate. It was concluded that the methods applied and studied provide better process understanding and knowledge of the drug products, and therefore, a way to achieve better quality.

Getting value out of your sensory testing - the difference from control test

Non-parametric difference tests such as triangle and duo-trio tests traditionally are used to establish differences or similarities between products. However they only supply the researcher with partial answers and often further testing is required to establish the nature, size and direction of differences. This paper looks at the advantages of the difference from control (DFC) test (also known as degree of difference test) and discusses appropriate applications of the test. The scope and principle of the test, panel composition and analysis of results are presented with the aid of suitable examples. Two of the major uses of the DFC test are in quality control and shelf-life testing. The role DFC takes in these areas and the use of other tests to complement the testing is discussed. Controls or standards are important in both these areas and the use of standard products, mental and written standards and blind controls are highlighted. The DFC test has applications in products where the duo-trio and triangle tests cannot be used because of the normal heterogeneity of the product. While the DFC test is a simple difference test it can be structured to give the researcher more valuable data and scope to make informed decisions about their product.

A Comparison of Methods for Describing Irregular Animal Growth and Testing for Treatment Effects

In many designed experiments with animals liveweight is recorded several times during the trial. Such data are commonly referred to as repeated measures data. An aim of such experiments is generally to compare the growth patterns for the applied treatments. This paper discusses some of the methods of analysing repeated measures data and illustrates the use of cubic smoothing splines to describe irregular cattle growth data. Animal production for a consuming world : proceedings of 9th Congress of the Asian-Australasian Association of Animal Production Societies [AAAP] and 23rd Biennial Conference of the Australian Society of Animal Production [ASAP] and 17th Annual Symposium of the University of Sydney, Dairy Research Foundation, [DRF]. 2-7 July 2000, Sydney, Australia.

Direct shear testing on unsaturated silty soils to investigate the effects of drying and wetting on shear strength parameters at low suction

A modified conventional direct shear device was used to measure unsaturated shear strength of two silty soils at low suction values (0 ~ 50 kPa) that were achieved by following drying and wetting paths of soil water characteristic curves (SWCCs). The results revealed that the internal friction angle of the soils was not significantly affected by either the suction or the drying wetting SWCCs. The apparent cohesion of soil increased with a decreasing rate as suction increased. Shear stress-shear displacement curves obtained from soil specimens subjected to the same net normal stress and different suction values showed a higher initial stiffness and a greater peak stress as suction increased. A soil in wetting exhibited slightly higher peak shear stress and more contractive volume change behavior than that of soil in drying at the same net normal stress and suction.