An Investigation of the Relationship Between the Second-to-Fourth Digit Ratio and Sagittal Synostosis.

BACKGROUND: The most common presentation of nonsyndromic craniosynostosis is that of the sagittal suture. Amongst this subgroup there is a significant male preponderance. Although the etiology is largely unknown, androgen exposure in utero has been suggested as a contributing factor. The second-to-fourth digit ratio (2D:4D) is a sexually dimorphic trait, reflective of the levels of androgen and estrogen exposure in utero, with a lower 2D:4D ratio associated with higher androgen exposure.This study aimed to examine the difference in 2D:4D ratio between participants with sagittal synostosis (SS) and gender- matched controls, hypothesizing that alterations in androgen exposure would be reflected in participants' 2D:4D ratio. METHOD: Participants with nonsyndromic SS and gender-matched controls were prospectively recruited from outpatients clinics. Photographs were taken of the right hand, and 3 independent researchers measured the length of the fingers and 2D:4D ratio, with the mean 2D:4D ratio then calculated. RESULTS: Fifty-six participants were recruited to both groups, with 35 males and 21 females in each. The mean age of the study and control groups were 5.6 and 6.3 years, respectively. There was no difference in the 2D:4D ratio between groups overall ( P = 0.126). However, males with SS had a significantly higher 2D:4D ratio in comparison to male controls (0.969 ± 0.379 versus 0.950 ± 0.354, P = 0.038). CONCLUSIONS: Our results suggest that 1 single hormonal pathway is not responsible for suture fusion. Subsequently we consider that an imbalance between testosterone and estrogen signaling may contribute to the development of sagittal craniosynostosis.

Equestrian Injury Presentations to a Regional Trauma Centre in Ireland.

Background: The Irish Equestrian industry provides over 12,500 full time job equivalents contributing in excess of €454 million to the Irish economy annually. For such an important industry there is a paucity of information relating to equestrian injuries. Aims: The aim of this study was to determine the demographics, characteristics, and outcomes of equestrian related injuries presenting to the emergency department of a regional trauma centre in Ireland over the course of one year. Methods: Retrospective analysis of all 30,700 presentations to the emergency department (ED) of the Midland Regional Hospital (MRH) Tullamore in 2013 was performed to identify equestrian related presentations. Patient demographics, mechanism of injury, radiology results, management, and follow-up data were collected and analysed using Microsoft Excel software. Results: A total of 149 equestrian related presentations were identified during the study period. There were significantly more females involved in equestrian injuries than males (58% versus 42%). Falling from a horse contributed to significantly more presentations and admissions than any other cause. 36% of presentations were associated with a radiological abnormality. Types of injuries identified included skeletal fractures (27.5%), joint dislocation/subluxation (5%), concussion (12.5%), and splenic laceration/intraperitoneal haemorrhage (1%). Admission or transfer to tertiary care was required for 18% of equestrian injuries. Only 43% of presentations were discharged back to primary care from the emergency department. Conclusion: This study identifies a high incidence of morbidities associated with equestrian presentations. In addition we recognised populations at risk of specific injuries and described high-risk mechanisms of injury.

A retrospective review of farm injuries presenting to an Irish hospital emergency department in 2013.

BACKGROUND: The agricultural and equestrian businesses are an important source of employment in the Midlands. This is a retrospective study examining the demographics, characteristics, and outcomes of agricultural and equestrian related injuries presenting to the Midland Regional Hospital, Tullamore, Co. Offaly. There were a total of 30,700 attendances to the Emergency Department for 2013. AIMS: This study is an epidemiological review of agricultural injuries, their mechanisms, and consequences presenting to a rural regional hospital over a 1 year period. METHODS: Every presentation to the Accident and Emergency Department at the Midlands Regional Hospital in 2013 was assessed retrospectively to determine if an injury had been sustained in an agricultural environment. Patient demographics, month of occurrence, mechanism of injury, radiology results, management, and follow-up data were collected and analysed using Microsoft Excel. RESULTS: There were 144 agricultural-related presentations to the Accident and Emergency Department. 23% of the agricultural injuries were identified as having a radiological abnormality. There were significantly more males involved in agricultural injuries than females (97 vs 3%). 16% of presentations required admission or transfer to tertiary specialist care and 8% required surgical intervention. Farming machinery accidents contributed to more admissions than any other cause in the agricultural category and resulted in more surgical interventions. CONCLUSION: Our study has identified high-risk mechanisms of injury, which should alert clinicians to the potential for significant injury. In addition, our findings could be used to help policy makers promote safety and awareness through public health policies that target high-risk practices with appropriate training and legislation.

A role for the outer retina in development of the intrinsic pupillary light reflex in mice.

Mice do not require the brain in order to maintain constricted pupils. However, little is known about this intrinsic pupillary light reflex (iPLR) beyond a requirement for melanopsin in the iris and an intact retinal ciliary marginal zone (CMZ). Here, we study the mouse iPLR in vitro and examine a potential role for outer retina (rods and cones) in this response. In wild-type mice the iPLR was absent at postnatal day 17 (P17), developing progressively from P21-P49. However, the iPLR only achieved ∼ 30% of the wild-type constriction in adult mice with severe outer retinal degeneration (rd and rdcl). Paradoxically, the iPLR increased significantly in retinal degenerate mice >1.5 years of age. This was accompanied by an increase in baseline pupil tone in the dark to levels indistinguishable from those in adult wild types. This rejuvenated iPLR response was slowed by atropine application, suggesting the involvement of cholinergic neurotransmission. We could find no evidence of an increase in melanopsin expression by quantitative PCR in the iris and ciliary body of aged retinal degenerates and a detailed anatomical analysis revealed a significant decline in melanopsin-positive intrinsically photosensitive retinal ganglion cells (ipRGCs) in rdcl mice >1.5 years. Adult mice lacking rod function (Gnat1(-/-)) also had a weak iPLR, while mice lacking functional cones (Cpfl5) maintained a robust response. We also identify an important role for pigmentation in the development of the mouse iPLR, with only a weak and transient response present in albino animals. Our results show that the iPLR in mice develops unexpectedly late and are consistent with a role for rods and pigmentation in the development of this response in mice. The enhancement of the iPLR in aged degenerate mice was extremely surprising but may have relevance to behavioral observations in mice and patients with retinitis pigmentosa.

The heat-shock response co-inducer arimoclomol protects against retinal degeneration in rhodopsin retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited diseases that cause blindness due to the progressive death of rod and cone photoreceptors in the retina. There are currently no effective treatments for RP. Inherited mutations in rhodopsin, the light-sensing protein of rod photoreceptor cells, are the most common cause of autosomal-dominant RP. The majority of mutations in rhodopsin, including the common P23H substitution, lead to protein misfolding, which is a feature in many neurodegenerative disorders. Previous studies have shown that upregulating molecular chaperone expression can delay disease progression in models of neurodegeneration. Here, we have explored the potential of the heat-shock protein co-inducer arimoclomol to ameliorate rhodopsin RP. In a cell model of P23H rod opsin RP, arimoclomol reduced P23H rod opsin aggregation and improved viability of mutant rhodopsin-expressing cells. In P23H rhodopsin transgenic rat models, pharmacological potentiation of the stress response with arimoclomol improved electroretinogram responses and prolonged photoreceptor survival, as assessed by measuring outer nuclear layer thickness in the retina. Furthermore, treated animal retinae showed improved photoreceptor outer segment structure and reduced rhodopsin aggregation compared with vehicle-treated controls. The heat-shock response (HSR) was activated in P23H retinae, and this was enhanced with arimoclomol treatment. Furthermore, the unfolded protein response (UPR), which is induced in P23H transgenic rats, was also enhanced in the retinae of arimoclomol-treated animals, suggesting that arimoclomol can potentiate the UPR as well as the HSR. These data suggest that pharmacological enhancement of cellular stress responses may be a potential treatment for rhodopsin RP and that arimoclomol could benefit diseases where ER stress is a factor.

Feasibility and acceptability of gentamicin in the Uniject prefilled injection system for community-based treatment of possible neonatal sepsis: the experience of female community health volunteers in Nepal.

OBJECTIVE: Explore feasibility and acceptability of gentamicin in the Uniject prefilled injection system, in combination with oral cotrimoxazole-p and an appropriate newborn weighing scale, for treatment of possible neonatal sepsis when administered in the community by female community health volunteers. STUDY DESIGN: In a community-based program in Nepal, 45 volunteers recorded 422 live births. Among these, 82 infants were identified as having possible severe bacterial infection. In all, 67 of these infants were treated with gentamicin in Uniject and 15 were referred to the health facility. Mixed methods were used to collect data about Uniject performance, acceptability and safety. RESULT: Volunteers successfully treated 67 infants with gentamicin in Uniject. Gentamicin in Uniject performed well and was acceptable. CONCLUSION: Gentamicin in Uniject, in combination with cotrimoxazole-p and an appropriate newborn weighing scale, is a feasible and acceptable option for treatment of possible neonatal sepsis in the community by female community health volunteers.

Risk factors for the occurrence of Escherichia coli virulence genes eae, stx1 and stx2 in wild bird populations.

Shiga toxin-producing Escherichia coli (STEC) can cause serious disease in human beings. Ruminants are considered to be the main reservoir of human STEC infections. However, STEC have also been isolated from other domestic animals, wild mammals and birds. We describe a cross-sectional study of wild birds in northern England to determine the prevalence of E. coli-containing genes that encode Shiga toxins (stx1 and stx2) and intimin (eae), important virulence determinants of STEC associated with human disease. Multivariable logistic regression analysis identified unique risk factors for the occurrence of each virulence gene in wild bird populations. The results of our study indicate that while wild birds are unlikely to be direct sources of STEC infections, they do represent a potential reservoir of virulence genes. This, coupled with their ability to act as long-distance vectors of STEC, means that wild birds have the potential to influence the spread and evolution of STEC.

New and underutilised technologies to reduce maternal mortality and morbidity: what progress have we made since Bellagio 2003?

In 2003, maternal health experts met in Bellagio, to consider new and underutilised technologies vital to pregnancy-related health services in low-resource settings. Five years later, we examine what progress has been made and what new opportunities may be on the horizon. Based on a review of literature and consultation with experts, we consider technologies addressing the five leading causes of maternal mortality: postpartum haemorrhage, eclampsia, obstructed labour, puerperal sepsis, and unsafe abortion (pregnancy termination and miscarriage). In addition, we consider technologies related to obstetric fistula, which has received more attention in recent years.

Women's participation in a cervical cancer screening program in northern Peru.

Cervical cancer is often the most common cancer among women in developing countries, yet current screening efforts have not been effective in reducing incidence and mortality rates in these settings. In an effort to increase knowledge about screening participation in low-resource settings, this study sought to identify key factors affecting women's participation in a cervical screening program in north central Peru. We studied women who were exposed to various health promotion educational activities and compared a total of 156 women who sought screening between July 2001 and October 2003 with 155 women who did not. Results from logistic regression identified four significant predictors of screening: higher relative wealth, knowing other screened women, seeking care from a health facility when sick and satisfaction with services at the health facility. When we restricted our analysis to women who had experienced screening in the past, two additional predictors emerged: having a husband who was supportive of screening participation and attending an awareness-raising session. These results have important programmatic value for tailoring outreach efforts for women and indicate that different strategies may be required to best reach women who have never been screened.

Preferences and practices: use of neonatal resuscitation devices in low-resource settings.

BACKGROUND: Birth asphyxia, when a baby does not breathe at birth, is estimated to account for 23% of the approximately four million neonatal deaths that occur annually. Correct use of neonatal resuscitators is critical to lower neonatal mortality rates due to birth asphyxia. METHODS: In order to understand the context of use of resuscitators including use scenarios, training, device readiness and design features and preferences, PATH conducted an anonymous web-based survey among neonatal health experts. Twenty-eight percent (22/80) of experts completed the survey. RESULTS: In general, the bag and mask devices were used by more practitioners and in more places than the tube and mask design; the tube and mask device was not well known. Features of the bag and mask device that mattered most were ease of use, mask size and device function. Features of the tube and mask device that mattered most were ease of use and availability. Device readiness at delivery and use of devices after long periods of inactivity were also concerns. CONCLUSIONS: There was a clear preference for the bag and mask device over the tube and mask device due to its ease of use. Programmatic implications include the need to improve health workers' confidence in the ability of the device to be cleaned and to remain in safe working order over time. These issues should be reviewed during periodic refresher training courses.

Validation of accuracy and community acceptance of the BIRTHweigh III scale for categorizing newborn weight in rural India.

OBJECTIVE: To determine the accuracy and acceptability of a handheld scale prototype designed for nonliterate users to classify newborns into three weight categories (>or=2,500 g; 2,000 to 2,499 g; and <2,000 g). STUDY DESIGN: Weights of 1,100 newborns in Uttar Pradesh, India, were measured on the test scale and validated against a gold standard. Mothers, family members and community health stakeholders were interviewed to assess the acceptability of the test scale. RESULT: The test scale was highly sensitive and specific at classifying newborn weight (normal weight: 95.3 and 96.3%, respectively; low birth weight: 90.4 and 99.2%, respectively; very low birth weight: 91.7 and 98.4%, respectively). It was the overall agreement of the community that the test scale was more practical and easier to interpret than the gold standard. CONCLUSION: The BIRTHweigh III scale accurately identifies low birth weight and very low birth weight newborns to target weight-specific interventions. The scale is extremely practical and useful for resource-poor settings, especially those with low levels of literacy.

Constant illumination causes spatially discrete dopamine depletion in the normal and degenerate retina.

A fully competent retinal dopamine system underpins normal visual function. Although this system is known to be compromised both prior to and during retinal degeneration, the spatial dynamics of dopamine turnover within the degenerate retina are at present unknown. Here, using immunohistochemistry for dopamine in combination with quantitative optical density measurements, we reveal a global decline in retinal dopamine levels in the light adapted RCS dystrophic rat, which is restricted to plexiform layers in the dark. Pharmacological blockade of dopamine production with the drug alpha-methyl-p-tyrosine (AMPT) allows the direct visualisation of dopamine depletion in normal and degenerate retina in response to constant illumination. In normal retinae this effect is spatially discrete, being undetectable in perikarya and specific to amacrine cell fibres in sublamina 1 of the inner plexiform layer. A similar response was observed in the retinae of dystrophic rats but with a reduction in amplitude of approximately 50%. It is suggested that the pattern of dopamine depletion observed in rat retina may reflect an AMPT-resistant pool of perikaryal dopamine and/or a reduction in extrasynaptic release of this neurotransmitter in response to illumination in vivo. We conclude that the visualisation of dopamine depletion reported here represents a release of this neurotransmitter in the response to light. Turnover of dopamine in the dystrophic retina is discussed in the context of surviving photoreceptors, including the intrinsically photosensitive melanopsin ganglion cells of the inner retina.

A low cost, colour coded, hand held spring scale accurately categorises birth weight in low resource settings.

AIMS: To determine the accuracy of a low cost, spring calibrated, hand held scale in classifying newborns into three weight categories (> or =2500 g, 2000-2499 g, <2000 g). METHODS: The test device was compared to a gold standard digital baby scale with precision to 2 g. In Sarlahi district, Nepal, 1890 newborns were eligible for the study. Measurements were collected for both the test device and the digital scale from 1820 (96.3%) newborns. RESULTS: The overall low birth weight (LBW) prevalence rate for the gold standard digital scale was 28.1% (511/1820). Sensitivity (93.7%) and specificity (97.6%) of the test device was high compared to LBW classifications based on digital weight measurements. Classification of infants into the <2000 g category was 5.0% and 4.7% for the gold standard and test device, respectively. Sensitivity and specificity of the test device in identifying infants <2000 g was 87.8% and 99.6%, respectively. Positive predictive values were high (>91%) for both weight categories CONCLUSIONS: This low cost, simple-to-use device classified infants into weight categories with a high degree of consistency and accuracy that exceeds that of surrogate measures. This new device is useful for identifying and targeting life saving interventions for LBW, high risk infants in settings where infants are born in the home and conventional weighing scales are unavailable.

Differentiation of an auditory neuronal cell line suitable for cell transplantation.

The auditory neuroblast cell line US/VOT-N33 (N33), which is conditionally immortal, was studied as an in vitro model for the differentiation of spiral ganglion neurons (SGNs) and as a candidate for cell transplantation in rodents. It expresses numerous molecular markers characteristic of auditory neuroblasts, including the transcription factors GATA3, NeuroD, Brn3a and Islet1, as well as the neuronal cytoskeletal protein beta3-tubulin. It displays active migratory behaviour in vitro and in vivo. In the presence of the fibroblast growth factors FGF1 or FGF2 it differentiates bipolar morphologies similar to those of native SGNs. In coculture with neonatal cochlear tissue it is repelled from epithelial surfaces but not from native SGNs, alongside which it extends parallel neuronal processes. When injected into the retina in vivo, EGFP-labelled N33 cells were traced for 1-2 weeks and migrated rapidly within the subretinal space. Cells that found their way into the retinal ganglion cell layer extended multiple processes but did not express beta3-tubulin. The ability of N33 to migrate, to differentiate, to localize with native SGNs in vitro and to survive in vivo suggests that they provide an effective model for SGN differentiation and for cell transplantation into the ear.

Involving the community in cervical cancer prevention programs.

Underutilization of cervical cancer prevention services by women in the high-risk age group of 30-60 years can be attributed to health service factors (such as poor availability, poor accessibility, and poor quality of care provided), to women's lack of information, and to cultural and behavioral barriers. The Alliance for Cervical Cancer Prevention (ACCP) partners have been working to identify effective ways to increase women's voluntary participation in prevention programs by testing strategies of community involvement in developing countries. The ACCP experiences include developing community partnerships to listen to and learn from the community, thereby enhancing appropriateness of services; developing culturally appropriate messages and educational materials; making access to high-quality screening services easier; and identifying effective ways to encourage women and their partners to complete diagnosis and treatment regimens. Cervical cancer prevention programs that use these strategies are more likely to increase demand, ensure follow-through for treatment, and ultimately reduce disease burden.

Retinotopy within rat primary visual cortex using optical imaging.

The purpose of this study was to determine the retinotopic organization of rat primary visual cortex (area 17) using optical imaging technology. Stimulating discrete regions of visual space resulted in localised changes in the remitted light during optical imaging of visual cortex in rat. From these localised changes, our results confirm previous electrophysiological studies on the location, size and organization of rat primary visual cortex. Small differences in the cortical magnification factor (CMF) were found between visual field areas with the highest CMF confined to the upper nasal region. No significant CMF differences were found within the horizontal and vertical visual field axes. No secondary visual areas were activated either anterior or medial to area 17 with the pattern stimuli used in the current study. However, there was evidence of activity to upper nasal stimulation on the posterior lateral extrastriate area. The location of area 17 from optical imaging activity was confirmed anatomically using conventional immunohistochemical techniques. This study shows the retinotopic organization of rat primary visual cortex and serves as a precursor before examining animal models of retinal degeneration and the effectiveness of potential therapies to stem retinal disease.

Identification of the odour and chemical composition of alumina refinery air emissions.

Alcoa World Alumina Australia has undertaken comprehensive air emissions monitoring aimed at characterising and quantifying the complete range of emissions to the atmosphere from Bayer refining of alumina at its Western Australian refineries. To the best of our knowledge, this project represents the most complete air emissions inventory of a Bayer refinery conducted in the worldwide alumina industry. It adds considerably to knowledge of air emission factors available for use in emissions estimation required under national pollutant release and transfer registers (NPRTs), such as the Toxic Releases Inventory, USA, and the National Pollutant Inventory, Australia. It also allows the preliminary identification of the key chemical components responsible for characteristic alumina refinery odours and the contribution of these components to the quality, or hedonic tone, of the odours. The strength and acceptability of refinery odours to employees and neighbours appears to be dependent upon where and in what proportion the odorous gases have been emitted from the refineries. This paper presents the results of the programme and develops a basis for classifying the odour properties of the key emission sources in the alumina-refining process.

Oxytocin in prefilled Uniject injection devices for managing third-stage labor in Indonesia.

We assessed the use and acceptability of an injection device (Uniject) prefilled with oxytocin, as part of active management of third-stage labor (AMTL) by Indonesian midwives attending home births. We interviewed 140 village midwives (bidan di desa) and 2220 mothers whose deliveries they attended during the intervention period. We completed baseline and post-intervention assessments to determine their experiences and views of oxytocin Uniject use. Delivery logs and supervisory reports were reviewed. The assessment was done in three rural districts and one municipality in Lombok. Injection practices and oxytocin availability did not change dramatically, although dose accuracy, use of sterile injection equipment, and proper disposal improved when the Uniject device was used. Midwives had little difficulty using the Uniject device properly; they overwhelmingly preferred it to standard needles and syringes. Postpartum hemorrhage rates did not change substantially. Oxytocin via Uniject holds promise for safer, more convenient use of oxytocin by trained midwives attending home deliveries, thereby potentially reducing the incidence of postpartum hemorrhage.

Long-term preservation of cortically dependent visual function in RCS rats by transplantation.

Cell transplantation is one way of limiting the progress of retinal degeneration in animal models of blinding diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Here we transplanted a human retinal pigment epithelial (RPE) cell line into the subretinal space of one such model, the Royal College of Surgeons (RCS) rat, and showed, using head tracking to moving stripes and pattern discrimination in conjunction with single-unit cortical physiology, that cortically mediated vision can be preserved with this treatment.

Basal increase in c-Fos-like expression in superior colliculus of Royal College of Surgeons dystrophic rats can be abolished by intraocular injection of tetrodotoxin.

In normal rats maintained in the dark, very few cells in the primary visual centers, including the superior colliculus, show Fos-like immunoreactivity. By contrast, in rats presented with flashing lights many Fos-like immunoreactivity cells are observed distributed throughout the visual centers. In the dystrophic Royal College of Surgeons rat, in which there is major loss of photoreceptors over the first 3 months of life, similar numbers of Fos-like immunoreactivity cells are seen on light presentation, but in marked contrast, cell densities in the rats maintained in the dark are many times higher than in non-dystrophic rats maintained under similar conditions. Here we show that this elevated dark response can be abolished by intravitreal injection of the sodium channel blocker tetrodotoxin, indicating that this effect results from changed retinal activity, rather than being centrally generated. We suggest that since Fos-like immunoreactivity is not usually elicited by steady state conditions, the elevated levels in the superior colliculus in these animals reflect the return of waves of activity, first seen in development coursing across the retina, but lost with photoreceptor maturation.