Secondary traumatisation, burn-out and functional impairment: findings from a study of Danish child protection workers.

Background: Child-protection workers are at elevated risk for secondary traumatization. However, research in the area of secondary traumatization has been hampered by two major obstacles: the use of measures that have unclear or inadequate psychometric properties and equivocal findings on the degree of associated functional impairment. Objective: To assess the relationship between secondary traumatization and burnout using exploratory structural equation modelling (ESEM) and to assess the relationship between secondary traumatization and functional impairment. Methods: A survey of Danish child-protection workers was conducted through the Danish Children Centres (N = 667). Secondary traumatization was measured using the Professional Quality of Life-5 (ProQoL-5) and burnout using the Oldenburg Burnout Inventory. Results: A three-factor ESEM model provided the best fit to the data, reflecting factors consistent with the structure of secondary traumatization and burnout. The factors were differentially related to trauma-related and organizational variables in ways consistent with existing evidence. All factors were significantly related to functional impairment. Conclusion: The findings supported the discriminant validity of secondary traumatization and burnout while highlighting methodological issues around the current use of sum-score approaches to investigating secondary traumatization. The current study supported the clinical relevance of secondary traumatization by linking it explicitly to social and cognitive functional impairment.

Antecedentes: los trabajadores de protección infantil tienen un riesgo elevado de traumatización secundaria. Sin embargo, la investigación en el área de la traumatización secundaria se ha visto obstaculizada por dos trabas principales: el uso de variables que tienen propiedades psicométricas poco claras o inadecuadas y hallazgos equívocos sobre el grado de deterioro funcional asociado.Objetivo: evaluar la relación entre la traumatización secundaria y el agotamiento utilizando el modelo exploratorio de ecuaciones estructurales (ESEM, por sus siglas en inglés) y evaluar la relación entre la traumatización secundaria y el deterioro funcional.Metodología: se realizó una encuesta a los trabajadores daneses de protección infantil a través de los Centros de Niños Daneses (N = 667). La traumatización secundaria se midió utilizando la Calidad de vida profesional-5 (ProQoL-5) y el agotamiento fue evaluado utilizando el Inventario de Agotamiento de Oldenburg.Resultados: Un modelo ESEM de tres factores proporcionó el mejor ajuste a los datos, reflejando factores consistentes con la estructura de la traumatización secundaria y el agotamiento. Los factores se relacionaron de manera diferencial con las variables relacionadas con el trauma y la organización, de manera consistente con la evidencia existente. Todos los factores estaban significativamente relacionados con el deterioro funcional.Conclusión: Los hallazgos respaldaron la validez discriminante de la traumatización secundaria y el agotamiento, al tiempo que resaltaron los problemas metodológicos en torno al uso actual de los enfoques de suma de puntajes para investigar la traumatización secundaria. El presente estudio apoyó la relevancia clínica de la traumatización secundaria al vincularla explícitamente con el deterioro funcional social y cognitivo.

Enhanced oral delivery of celecoxib via the development of a supersaturable amorphous formulation utilising mesoporous silica and co-loaded HPMCAS.

Stabilization of amorphous formulations via mesoporous silica has gained considerable attention for oral delivery of poorly soluble drugs. The release of the drug from the silica is expected to generate supersaturation which is often associated with subsequent precipitation. The aim of the study was hence to develop a novel supersaturable amorphous formulation through the co-loading of a BCS class II drug Celecoxib (CXB) with a precipitation inhibitor hydroxypropyl methylcellulose acetate succinate (HPMCAS) onto the silica. The addition of HPMCAS did not hamper the adsorption but on the contrary promoted the complete solid state conversion of the drug as proved by DSC analysis. In an in vitro pH shift assay, the CXB-HPMCAS co-loaded silica achieved a 5-fold solubility increase over the crystalline CXB and over the CXB-loaded silica blended with HPMCAS which did not show any enhancement. The drug co-loaded silica was then suspended in an aqueous vehicle facilitating the dosing to animals. The CXB-HPMCAS co-loaded silica suspension achieved 15-fold solubility increase in vitro over the crystalline counterpart which translated in 1.35-fold Cmax increase in vivo after oral dosing in rats. This approach represents a novel formulation strategy to maximize in vivo exposure of poorly soluble drugs critical for discovery studies.

First-generation linkage map of the warningly colored butterfly Heliconius erato.

We report the first genetic linkage map of Heliconius erato, a species that shows remarkable variation in its warningly colored wing patterns. We use crosses between H. erato and its sister species, H. himera, to place two major color pattern genes, D and Cr, on a linkage map containing AFLP, allozyme, microsatellite and single-copy nuclear loci. We identified all 21 linkage groups in an initial genetic screen of 22 progeny from an F1 female x male H. himera family. Of the 229 markers, 87 used to identify linkage groups were also informative in 35 progeny from a sibling backcross (H. himera female x F1 male). With these, and an additional 33 markers informative in the second family, we constructed recombinational maps for 19 of the 21 linkage groups. These maps varied in length from 18.1 to 431.1 centimorgans (cM) and yielded an estimated total length of 2400 cM. The average distance between markers was 23 cM, and eight of the 19 linkage groups, including the sex chromosome (Z) and the chromosome containing the Cr locus, contained two or more codominant anchor loci. Of the three potential candidate genes mapped here, Cubitus interruptus (Ci), Decapentaplegic (Dpp) and Wingless (Wg), only Ci was linked, although loosely, to a known Heliconius color pattern locus. This work is an important first step for constructing a denser genetic map of the H. erato color pattern radiation and for a comparative genomic study of the architecture of mimicry in Heliconius butterflies.

Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo.

BACKGROUND: Terahertz radiation lies between the infrared and microwave regions of the electromagnetic spectrum and can be used to excite large amplitude vibrational modes of molecules and probe the weak interactions between them. Terahertz pulsed imaging (TPI) is a noninvasive imaging technique that utilises this radiation. OBJECTIVES: To determine whether TPI could differentiate between basal cell carcinoma (BCC) and normal tissue and to test whether it can help facilitate delineation of tumour margins prior to surgery. METHODS: A portable TPI system was used in the clinic to image 18 BCCs ex vivo and five in vivo. RESULTS: The diseased tissue showed a change in terahertz properties compared with normal tissue, manifested through a broadening of the reflected terahertz pulse. Regions of disease identified in the terahertz image correlated well with histology. CONCLUSIONS: This study has confirmed the potential of TPI to identify the extent of BCC in vivo and to delineate tumour margins. Further clinical study of TPI as a surgical tool is now required.

Historical demography of Mullerian mimicry in the neotropical Heliconius butterflies.

We compare the historical demographies of two Müllerian comimetic butterfly species: Heliconius erato and Heliconius melpomene. These species show an extensive parallel geographic divergence in their aposematic wing phenotypes. Recent studies suggest that this coincident mosaic results from simultaneous demographic processes shaped by extrinsic forces over Pleistocene climate fluctuations. However, DNA sequence variation at two rapidly evolving unlinked nuclear loci, Mannose phosphate isomerase (Mpi) and Triose phosphate isomerase (Tpi), show that the comimetic species have quite different quaternary demographies. In H. erato, despite ongoing lineage sorting across the Andes, nuclear genealogical estimates showed little geographical structure, suggesting high historical gene flow. Coalescent-based demographic analysis revealed population growth since the Pliocene period. Although these patterns suggest vicariant population subdivision associated with the Andean orogeny, they are not consistent with hypotheses of Pleistocene population fragmentation facilitating allopatric wing phenotype radiation in H. erato. In contrast, nuclear genetic diversity, theta, in H. melpomene was reduced relative to its comimic and revealed three phylogeographical clades. The pattern of coalescent events within regional clades was most consistent with population growth in relatively isolated populations after a recent period of restricted population size. These different demographic histories suggest that the wing-pattern radiations were not coincident in the two species. Instead, larger effective population size (N(e)) in H. erato, together with profound population change in H. melpomene, supports an earlier hypothesis that H. erato diversified first as the model species of this remarkable mimetic association.

Visual impairment in childhood: insights from a community-based survey.

BACKGROUND: The concept of visual impairment (VI) in childhood has changed over the last 30 years. There has been a decrease in the number of children with an isolated visual problem and an increase in the numbers with VI and coexisting neurological disability. This study aimed to produce a profile of VI in childhood with a view to informing future services and to raise awareness of the need for comprehensive assessment including developmental remediation and educational advice. METHODS: Children with a VI were identified from multiple sources including hospital- and community-based paediatricians and statutory blind registers. RESULTS: Seventy-six children with a VI were identified giving a childhood prevalence of 1.61 per 1000. Thirty-two per cent had a normal pattern of development. Global delays/severe learning difficulty were found in 43%. Only 21% of the children had an isolated VI. Additional medical problems were present in 79% of which cerebral palsy, occurring in 33%, was the most common. Nine per cent of the children were classified as totally blind. Cortical visual impairment was diagnosed in 45%. Twenty-two per cent of the children were registered blind or partially sighted. CONCLUSIONS: Most cases of VI in children did not appear on the statutory blind or partially sighted registers, thus these have limited value for service development. The implications for practice highlight the need for early assessment and advice from a co-ordinated team to optimize visual potential in childhood.

The Child Protection Register: a tool in the accident and emergency department?

AIMS: To determine the number of children on the Child Protection Register (CPR) attending the accident and emergency (A&E) department and the referral source, diagnostic category, and frequency distribution for such attendances. To determine whether lack of knowledge that a child is on the CPR results in failure to suspect non-accidental injury (NAI) if the standard indicators of NAI have been sought. METHODS: Access to the CPR was obtained. Records of each child attending the A&E departments of the United Hospitals Trust between June 1994 and May 2000 were reviewed. RESULTS: Over the six years 191 children were on the CPR. Seventy nine (41%) attended A&E departments on 206 occasions. Frequency of attendance ranged to 18 with a mean of 2.6. Self referral was the commonest source of referral (81%) followed by general practitioners (13%), 999 calls (5%), and a small number from schools (1%). Most presentations involved trauma-upper limb (21%), lower limb (14%), and head injury (8%). Almost all cases of trauma were adjudged to be consistent with the history and NAI not suspected. Common childhood illnesses accounted for the remainder of presentations. Only six children were identified as being on the CPR at the time of presentation. Concerns were raised in two other cases and concerns should have been raised in three other children. Social Services were alerted on five occasions directly by the parents themselves. CONCLUSIONS: It is concluded that in the absence of knowledge of the status of a child on the CPR attending the A&E department, that screening for the standard indicators of NAI is adequate to detect most cases of NAI.

The relation between melanocortin 1 receptor genotype and experimentally assessed ultraviolet radiation sensitivity.

Pigmentary phenotype is a key determinant of an individual's response to ultraviolet radiation with the presence of phaeomelanin thought to be of particular importance. Reports of minimal erythema testing, however, have failed to show a consistent difference between skin type I and other skin types. The melanocortin 1 receptor is a key genetic determinant of the cutaneous response to ultraviolet radiation. In this study we investigate the relation between experimentally induced erythemal response to ultraviolet radiation and the melanocortin 1 receptor genotype. Phototesting was performed in 20 redheads and 20 nonredheaded subjects, the majority of whom were also screened for the presence of melanocortin 1 receptor variants. The majority of redheads sequenced (89%) had two melanocortin 1 receptor variants previously found to be associated with red hair compared to none of the controls. There was no significant difference between the groups in minimal erythema dose: the median minimal erythema dose in redheads was 44 mJ per cm2 (interquartile range 34-56) and in the nonredheaded group was 40 mJ per cm2 (interquartile range 40-56). Objective measurements of ultraviolet-B-induced erythema were performed using reflectance instrument measurements of erythema intensity and dose-response curves constructed for each subject. The slope of the dose-response curve in the redheaded group was statistically greater than in the nonredheaded group (median in redheads 4.08 vs 3.56 for controls, 95% confidence interval for the difference between the medians being 0.01-1.23, p = 0.043). In addition the ratio D0.05:D0.025 was significantly lower for the redheaded group (median in redheads 1.22, interquartile range 1.18-1.26; median in nonreds 1.28, interquartile range 1.23-1.32; p < 0.05). Thus, although the minimal erythema dose values were not different, subjects with red hair develop greater intensity of erythema than nonredheaded individuals when doses greater than the minimal erythema dose are given. Importantly, when analyzed by genotype alone rather than phenotype, the slope of the erythema dose-response differed between those persons who were homozygous or heterozygous mutants and wildtype/pseudo-wildtype (p = 0.026).

Microsatellite variation in the yellowhammer Emberiza citrinella: population structure of a declining farmland bird.

In recent years, there has been much concern in the UK about population declines of widespread species in agricultural habitats. Conservation-orientated research on declining birds has focused on vital rates of survival and productivity. However, the environmental factors which may influence movements between populations of widespread species is poorly understood. Population genetic structure is an indirect description of dispersal between groups of individuals. To attempt to develop an understanding of genetic structuring in a widespread, but declining, farmland bird, we therefore investigated the yellowhammer, Emberiza citrinella, population in England and Wales using microsatellite data. Our first aim was to investigate whether there was genetic substructuring in the population. A second aim was to investigate if there was a relationship between genetic distances and various environmental variables. Finally, we analysed the microsatellite data for evidence of loss of genetic variation due to population decline. Our data showed a slight but significant structure within the yellowhammer population. This therefore cannot be considered a panmictic population. Our example from South Cumbria implies that high-altitude barriers may have a slight influence on population structure. However, on the whole, genetic distances between sample sites were not significantly correlated with geographical distances, degrees of population connectivity, high altitudes, or differences in precipitation between sites. Finally, we detected departures from mutation-drift equilibrium (excess heterozygosity), which is indicative of a loss of genetic variation through recent decline.

Pseudo-Kaposi's sarcoma: the association of arterio-venous malformations with skin lesions resembling Kaposi's sarcoma.

A patient is described with skin lesions resembling Kaposi's sarcoma (KS). Arteriography revealed multiple arteriovenous malformations in the affected limb. This condition has been termed pseudo-Kaposi's sarcoma. Although reports of this condition have appeared in dermatological journals, as yet we are unaware of any account in the radiological literature. This paper presents a case and reviews the literature. In suspected cases of KS in which the history or clinical features are atypical, this unusual condition should be considered and a search made for the diagnostic vascular lesions.

Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation.

Variants of the melanocortin 1 receptor (MC1R) gene are common in individuals with red hair and fair skin, but the relative contribution to these pigmentary traits in heterozygotes, homozygotes and compound heterozygotes for variants at this locus from the multiple alleles present in Caucasian populations is unclear. We have investigated 174 individuals from 11 large kindreds with a preponderance of red hair and an additional 99 unrelated redheads, for MC1R variants and have confirmed that red hair is usually inherited as a recessive characteristic with the R151C, R160W, D294H, R142H, 86insA and 537insC alleles at this locus. The V60L variant, which is common in the population may act as a partially penetrant recessive allele. These individuals plus 167 randomly ascertained Caucasians demonstrate that heterozygotes for two alleles, R151C and 537insC, have a significantly elevated risk of red hair. The shade of red hair frequently differs in heterozygotes from that in homozygotes/compound heterozygotes and there is also evidence for a heterozygote effect on beard hair colour, skin type and freckling. The data provide evidence for a dosage effect of MC1R variants on hair as well as skin colour.

Enriched eggs as a source of N-3 polyunsaturated fatty acids for humans.

Dietary intake of omega-3 fatty acids (n-3 PUFA) decreases the risk of heart disease, inhibits the growth of prostate and breast cancer, delays the loss of immunological functions, and is required for normal fetal brain and visual development. The US has not established a recommended daily intake for n-3 PUFA. However, Canada has established the Canadian Recommended Nutrient Intake (CRNI) at 0.5% of energy. Dietary sources of n-3 PUFA include fish, chicken, eggs, canola oil, and soybean oil. Food consumption studies in the US indicate that the majority of Americans do not meet the CRNI for n-3 PUFA. Mean n-3 PUFA consumption was 78% of the CRNI for Midwestern women during pregnancy. In Midwestern women at risk for breast cancer, the mean n-3 PUFA consumption is approximately 50% of the CRNI. Increased consumption of n-3 PUFA requires identification of a food source that the public would eat in sufficient amounts to meet recommended intake. N-3 PUFA-enriched eggs can be produced by modifying hens diets. When 70 g/kg of cod liver oil, canola oil, or linseed oil are added to a commercial control diet, the n-3 PUFA are increased from 1.2% of egg yolk fatty acids to 6.3, 4.6, and 7.8%, respectively. Feeding flaxseed increases linolenic acid in the egg yolk about 30-fold, and docosahexaenoic acid (DHA) increases nearly fourfold. When individuals are fed four n-3 PUFA-enriched eggs a day for 4 wk, plasma total cholesterol levels and low-density lipoprotein cholesterol (LDL-C) do not increase significantly. Plasma triglycerides (TG) are decreased by addition of n-3 PUFA-enriched eggs to the diet. N-3 PUFA may influence LDL particle size, causing a shift toward a less atherogenic particle. Blood platelet aggregation is significantly decreased in participants consuming n-3 PUFA-enriched eggs. Overall results of studies to date demonstrate positive effects and no negative effects from consumption of n-3-enriched eggs. Three n-3 PUFA-enriched eggs provide approximately the same amount of n-3 PUFA as one meal with fish. It is recommended that n-3 PUFA-enriched eggs be used as one source of n-3 PUFA to increase individual consumption to meet the current Canadian recommendations.

Severe skin rash in two consecutive patients treated with 2-chlorodeoxyadenosine for hairy cell leukaemia at a single institution.

Although hairy cell leukaemia was first described 40 years ago, it is only in the last decade that newer therapeutic agents have enabled effective treatment. The purine nucleoside analogue, 2-chlorodeoxyadenosine (2-CdA) is currently considered as first-line therapy with a very high rate of complete remission. Although adverse events with 2-CdA are increasingly recognized, severe cutaneous reactions have been reported rarely. We describe two consecutive patients treated with 2-CdA for hairy cell leukaemia who both suffered extremely severe cutaneous reactions, one of which was life-threatening.

Evidence for variable selective pressures at MC1R.

It is widely assumed that genes that influence variation in skin and hair pigmentation are under selection. To date, the melanocortin 1 receptor (MC1R) is the only gene identified that explains substantial phenotypic variance in human pigmentation. Here we investigate MC1R polymorphism in several populations, for evidence of selection. We conclude that MC1R is under strong functional constraint in Africa, where any diversion from eumelanin production (black pigmentation) appears to be evolutionarily deleterious. Although many of the MC1R amino acid variants observed in non-African populations do affect MC1R function and contribute to high levels of MC1R diversity in Europeans, we found no evidence, in either the magnitude or the patterns of diversity, for its enhancement by selection; rather, our analyses show that levels of MC1R polymorphism simply reflect neutral expectations under relaxation of strong functional constraint outside Africa.

Low frequency of genetic change in p53 immunopositive clones in human epidermis.

Sun-exposed skin of Caucasians harbors thousands of p53-mutated clones, which are clinically invisible. Using whole mount immunostaining for p53 or Ki67 antigens, p53 sequencing, and loss of heterozygosity analysis, we have further characterised these clones. Loss of heterozygosity for the alleles examined is uncommon with the exception of 9q, which occurred in 28.3% of the samples. P53 clones are more common and larger in individuals with basal cell carcinoma than in control subjects (p < 0.03). Loss of heterozygosity is also more common in clones from individuals with basal cell carcinoma than in clones from subjects without a history of basal cell carcinoma, as would be expected if both relate to ultraviolet radiation exposure. p53 sequencing of clones is in keeping with the mutagenic role of ultraviolet radiation. Surprisingly, skin found to harbor p53 clones showed no clusters of Ki67 positive cells, unlike the situation for actinic keratoses or basal cell carcinomas. These results show that in human skin p53 mutation is not directly associated with genomic instability or abnormal cell cycling; that the p53 immunopositive clones are either genetically distinct or precursors to other squamous cell lesions of skin; and that p53 immunopositive clones are early lesions, in that gross disturbance of proliferation has not already occurred.