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Background: The Northern Ireland Registry of Deliberate Self-Harm was established as an outcome of the Northern Ireland Suicide Prevention Strategy and Action Plan - Protect Life, beginning in the Western Health and Social Care Trust area. Aims: The study aimed to establish the incidence of hospital-treated deliberate self-harm in the Western Area of Northern Ireland, and to explore the profile of such presentations. Method: Deliberate self-harm presentations made to the three hospital emergency departments operating in the area during the period 2007-2012 were recorded. Results: There were 8,175 deliberate self-harm presentations by 4,733 individuals. Respectively, the total, male, and female age-standardized incidence rate was 342, 320, and 366 per 100,000 population. City council residents had a far higher self-harm rate. The peak rate for women was among 15-19-year-olds (837 per 100,000) and for men was among 20-24-year-olds (809 per 100,000). Risk of repetition was higher in 35-44-year-old patients if self-cutting was involved, but was most strongly associated with the number of previous self-harm presentations. Conclusion: The incidence of hospital-treated self-harm in Northern Ireland is far higher than in the Republic of Ireland and more comparable to that in England.

Purpose: To report the prevalence of gonococcal conjunctivitis (GC) presenting to a tertiary referral maternity hospital (NMH) and a tertiary referral ophthalmic hospital (RVEEH) from 2011 to 2013 and describe the demographics, clinical presentation, and antibiotic susceptibility of Neisseria gonorrhoeae ocular infections., Methods: Demographic, clinical, and microbiological data were collected from patients with laboratory confirmed GC., Results: There were 27 556 live births at NMH during the study period, and no case of neonatal GC was identified. Fourteen cases of GC were identified at RVEEH in this period, representing a prevalence of 0.19 cases per 1000 eye emergency attendees. Antibiotic susceptibility data were available on nine cases, of which, all were ceftriaxone- and ciprofloxacin sensitive. 64.3% of patients were male, with a mean age of 18 years. The mean duration of symptoms was 3 days. All patients presented with unilateral conjunctival injection and purulent discharge. Eight cases had visual impairment at presentation and their mean visual acuity was 6/15. Corneal involvement was present in 25% of patients. Uveitis was not detected. On receipt of positive culture and/or PCR results, treatment was altered in two thirds of patients. All patients were referred for full STI screening and all patients showed a full clinical recovery 1 week posttreatment., Conclusion: We observed that GC presented in young adults with a male predominance and was rare in neonates. In cases of unilateral purulent conjunctivitis, there should be a high clinical suspicion of GC, early swab for PCR and culture, and knowledge of current CDC-recommended antibiotic guidelines.

Caenorhabditis elegans can be infected by a plethora of pathogens, most of them are also pathogenic for humans. Consequently, the nematode has emerged as a powerful surrogate host to model microbial human infectious diseases in a non-vertebrate, for the study of innate immunity and host-pathogen interactions. Signaling cascades are well investigated that face bacterial or fungal pathogens. We analyzed the downstream processes of these cascades, i.e. the differential expression of effector and regulatory molecules due to a microbial challenge with a pathogenic strain of the bacterium Bacillus thuringiensis (Bt) in comparison to a non-pathogenic Bt strain. The protein abundance profile of the nematode was studied by quantitative proteomics using iTRAQ labeling and 2D-LC-MS analysis. We developed (i) a novel method for the preparation of defined C. elegans samples; (ii) a pooling strategy for fractions in 2D-LC separation schemes; and (iii) an isobaric labeling scheme reducing the number of necessary LC-MS experiments. More than 3,600 proteins were quantified, 288 of which showed altered abundances, implicating protein classes such as lectins, lysozymes, and transthyretin-like proteins to be involved in the nematode innate immune defense. A number of gene products previously only identified by transcriptomic profiling could be verified at the protein level. Moreover, several other protein classes such as proteases, proteins related to autophagy and apoptosis, structural proteins, and proteins involved in chromatin organization were detected. The results provide an overview of the physiological response towards a pathogen at protein level in the important model organism C. elegans, giving insights into highly complex host-pathogen interactions., Biological Significance: This study identified system-wide effects of Bt intoxication on C. elegans at protein level, expanding the catalogue of immune effectors potentially acting towards the pathogen, and provide verification for numerous gene products implicated in previous transcriptomic studies. The data present evidence in support of both a general defense response as well as a specific reaction against the Bt toxin within the nematode. The described findings will also contribute to a deeper understanding of host-microbe interaction in other organisms, including humans, and may provide key information that touches far reaching aspects of coevolutionary processes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Tracheobronchial variations can be found during routine bronchoscopy or computed tomography. Previous sources estimate an incidence of 1-12%; however, these variations are often asymptomatic. Symptomatic patients present typically with cough and lower respiratory tract infection. Knowledge and understanding of tracheobronchial variations have important implications for diagnosis of symptomatic patients and performing certain procedures, including bronchoscopy and endotracheal intubation. In this review, we describe the most commonly encountered variations, tracheal bronchus and accessory cardiac bronchus, along with three minor abnormalities of this region. We also review the various imaging modalities in the diagnosis and treatment of these conditions., (© 2014 Wiley Periodicals, Inc.)

All organisms live in constant contact with the microbial world. In recent years it has become evident that these microbial communities are not only responsible for the development of certain diseases, but are also an indispensable factor for homeostasis. The inherent complexity of meta-organisms hampers a straightforward elucidation of the molecular processes regulating the interactions of the host and its microbiome, as well as the influence of exogenic factors, for example, nutrition. Modern approaches such as meta-proteomics are now capable of deciphering the major processes in microbial communities, but the complete analysis of their interactions with their host is still in its infancy. In order to get easier access, the study of nonmammalian model organisms bears great potential. These organisms provide advantages such as reduced complexity, ease of cultivation in great numbers, and amenity to a range of genetic and biochemical manipulations. We highlight the potentials provided by model organism proteomics for the study of host-microbiome interactions and outline major challenges and demands for technological improvements that will be necessary for the understanding of the manifold interactions within meta-organisms., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Friedrich Trendelenburg's name is widely known today because it is associated with the Trendelenburg position. However, Trendelenburg made many other valuable contributions to the field of medicine, including a test, a gait, and a sign. A historical review of his life helps to elucidate the factors that contributed to his innovative approaches and techniques. Both Trendelenburg's mentors in his early years and the influences upon him throughout his professional career contributed to his development as a pioneer of surgery, anesthesia, and clinical diagnostics., (© 2014 Wiley Periodicals, Inc.)

Objectives: This study compared the profile of intentional drug overdoses (IDOs) presenting to emergency departments in Ireland and in the Western Trust Area of Northern Ireland between 2007 and 2012. Specifically the study aimed to compare characteristics of the patients involved, to explore the factors associated with repeated IDO and to report the prescription rates of common drug types in the population., Methods: We utilised data from two comparable registries which monitor the incidence of hospital-treated self-harm, recording data from deliberate self-harm presentations involving an IDO to all hospital emergency departments for the period 1 January 2007 to 31 December 2012., Results: Between 2007 and 2012 the registries recorded 56 494 self-harm presentations involving an IDO. The study showed that hospital-treated IDO was almost twice as common in Northern Ireland than in Ireland (278 vs 156/100 000, respectively)., Conclusions: Despite the overall difference in the rates of IDO, the profile of such presentations was remarkably similar in both countries. Minor tranquillisers were the drugs most commonly involved in IDOs. National campaigns are required to address the availability and misuse of minor tranquillisers, both prescribed and non-prescribed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

This article discusses the appearance of the "aortic nipple" in chest radiography, and reviews the embryology and anatomy of the left superior intercostal vein which causes the appearance of an "aortic nipple." This radiological sign is useful in differentiating certain thoracic pathologies, such as pneumomediastinum, pneumopericardium, and medial pneumothorax. Pneumomediastinum is an encompassing term describing the presence of air in the mediastinum, and may arise from a wide range of pathological conditions. Despite the well-described imaging of pneumomediastinum, it is sometimes difficult to differentiate from other conditions such as pneumopericardium and medial pneumothorax. A separate finding, "aortic nipple" is the radiographic term used to describe the lateral nipple-like projection from the aortic knob present in a small number of individuals. The aortic nipple corresponds to the end-on appearance of the left superior intercostal vein coursing around the aortic knob, and may be mistaken radiologically for lymphadenopathy or a neoplasm. Despite their relative independence, the aortic nipple is defined by new contours in cases of pneumomediastinum, taking on an "inverted aortic nipple" appearance. In this position, the inverted aortic nipple may facilitate radiographic discrimination of pneumomediastinum from similar conditions. This study aims to review the common clinical and radiographic features of both pneumomediastinum and the aortic nipple. The radiologic appearance of the aortic nipple occurring in unison with pneumomediastinum, and its potential role as a tool in the differentiation of pneumomediastinum from similarly presenting conditions will also be described., (Copyright © 2013 Wiley Periodicals, Inc.)

A Disintegrin and Metalloproteinase 10 (ADAM10) and ADAM17 catalyze ectodomain shedding of a number of cell surface proteins important for embryonic development and tissue homeostasis. Changes in the expression levels or dysregulated proteolytic activity of ADAM10 and ADAM17 have been shown to play important roles in multiple diseases such as inflammation, cancer, and neurodegenerative disorders. Despite the well documented substrate repertoire of ADAM10 and ADAM17, little is known about their cleavage site specificity. We optimized Q-PICS (Quantitative Proteomics for the Identification of Cleavage Sites) to elucidate the cleavage site specificity of recombinant murine ADAM10 and ADAM17. Two different yeast proteome-derived peptide libraries were used and samples were analyzed by LC-MALDI and LC-ESI MS in parallel. We show that the largest difference in the cleavage site specificities of ADAM10 and ADAM17 is at the P1' site: while both enzymes cleave N-terminal of leucine, only ADAM10 shows additional preference toward aromatic amino acids, whereas ADAM17 exhibits the highest preference for valine. Together with further amino acid preferences more adjacent to the scissile bond, our data is in good agreement with ADAM10/17 cleavage sites previously identified in native substrates. Overall, the precise identification of ADAM10 and ADAM17 cleavage site specificity provides the basis for better substrate identification in vivo and the generation of specific inhibitors or activity based probes.

Background: Information regarding the use of negative pressure wound therapy (NPWT) in the pediatric population is limited. Because of adverse outcomes in adult patients, the Food and Drug Administration issued a warning in 2011 about the use of NPWT in infants and children., Methods: We performed an institutional review board-approved, single-institution, retrospective review of pediatric patients who had undergone NPWT from 2007-2011. We collected the types of wounds for which NPWT was initiated, the NPWT outcomes, and the complications encountered., Results: The data from 290 consecutive patients were reviewed. Their average age was 9.3 y (range 12 d to 18 y), and their average weight was 46.5 kg (range 1.1-177). Of the wounds, 66% were classified as acute, 10% as chronic, and 24% as traumatic. The two most common indications were surgical wound dehiscence (n = 47) and skin grafting (n = 41). NPWT was used in 15 wounds containing surgical hardware, with 2 devices requiring eventual removal. NPWT was used for a median of 9 d per patient (two dressing changes). Complications occurred in 5 patients (1.7%). Documentation problems were noted in 44 patients. After NPWT, about one-third of the patients (n = 95 patients) were able to undergo delayed primary closure., Conclusions: NPWT is an effective adjunct in wound healing and closure in the pediatric population, with no mortality ascribed to NPWT. Also, the complication rates were low., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: There is increasing evidence linking vitamin D deficiency to both susceptibility to, and severity of, multiple sclerosis (MS). Patients with the clinically isolated syndrome represent the initial presentation of a demyelinating disorder, and those with asymptomatic lesions on magnetic resonance imaging (MRI) are at risk of progression to clinically definite MS. The aims of this study are to examine the immunologic effects of vitamin D in both healthy individuals and in patients with clinically isolated syndrome, and in the latter group the effects on disease progression assessed by MRI and clinical measures., Methods/design: This is a single-center double-blind randomized placebo-controlled clinical trial. The primary endpoint is the immunologic effects of two doses of vitamin D compared with placebo over 24 weeks in both healthy control participants and patients presenting with the clinically isolated syndrome. Healthy control participants (n = 39) and patients with clinically isolated syndrome (n = 45) will be randomized to one of three arms, namely 1) vitamin D 5,000 IU daily, 2) vitamin D 10,000 IU daily, or 3) placebo, and followed up for 24 weeks. In both patients and healthy control participants, the primary outcome will be immunologic measures of the frequency of CD4 T-cell subsets and cytokine responses in peripheral blood mononuclear cells, assessed at baseline, and after 16 and 24 weeks of treatment. Secondary endpoints, in the patients with clinically isolated syndrome, will be relapse activity, and the number of new T2 lesions and gadolinium-enhancing lesions assessed by MRI in the two vitamin D-treated groups compared with the placebo-treated group over the 24 weeks of the study., Trial Registration: EU Clinical Trials Register: EudraCT: 2012-000635-68. ClinicalTrials.gov identifier: NCT01728922.

Protein phosphorylation is an important post-translational modification that plays a regulatory role within numerous biological processes. The simultaneous identification, localization, and quantification of phosphorylated proteins is vital for understanding this dynamic control mechanism. The application of isobaric labeling strategies, for example, iTRAQ, for quantitative phosphopeptide analysis requires simultaneous monitoring of peptide backbone fragmentation, loss of phosphoryl moieties, and the cleavage of isobaric labeling reporter ions. In the present study, we have examined MS/MS fragmentation modes available in the Orbitrap Velos MS (collision induced dissociation (CID), CID plus multistage activation, and higher energy collision dissociation (HCD)), for their ability to generate ions required for simultaneous quantification and identification of iTRAQ labeled phosphopeptides in a semicomplex (12) and a complex (131) phosphopeptide mix. The required normalized collision energies for quantification and identification of iTRAQ-labeled phosphopeptides require a compromise between the optimal parameters for each aspect. Here, we were able to determine an optimized MS/MS measurement protocol that involves CID measurement in ion trap for identification followed by HCD measurement for parallel identification and quantification that satisfies the time requirements for LC-MS/MS experiments.

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Pluripotent stem cell markers can be useful for diagnostic evaluation of human tumors. The novel pluripotent marker stage-specific embryonic antigen-5 (SSEA-5) is expressed in undifferentiated human induced pluripotent cells (iPSCs), but little is known about SSEA-5 expression in other primitive tissues (e.g., human tumors). We evaluated SSEA-5 immunoreactivity patterns in human tumors, cell lines, teratomas, and iPS cells together with another pluripotent cell surface marker L1 cell adhesion molecule (L1CAM). We tested two hypotheses: (1) SSEA-5 and L1CAM would be immunoreactive and colocalized in human tumors; (2) SSEA-5 and L1CAM immunoreactivity would persist in iPSCs following retinal differentiating treatment. SSEA-5 immunofluorescence was most pronounced in primitive tumors, such as embryonal carcinoma. In tumor cell lines, SSEA-5 was highly immunoreactive in Capan-1 cells, while L1CAM was highly immunoreactive in U87MG cells. SSEA-5 and L1CAM showed colocalization in undifferentiated iPSCs, with immunopositive iPSCs remaining after 20 days of retinal differentiating treatment. This is the first demonstration of SSEA-5 immunoreactivity in human tumors and the first indication of SSEA-5 and L1CAM colocalization. SSEA-5 and L1CAM warrant further investigation as potentially useful tumor markers for histological evaluation or as markers to monitor the presence of undifferentiated cells in iPSC populations prior to therapeutic use.

Objective: The optimal treatment of necrotizing enterocolitis (NEC) is a common challenge for pediatric surgeons. Although many studies have evaluated prevention and medical therapy for NEC, few guidelines for surgical care exist. The aim of this systematic review is to review and evaluate the currently available evidence for the surgical care of patients with NEC., Methods: Data were compiled from a search of PubMed, OVID, the Cochrane Library database, and Web of Science from January 1985 until December 2011. Publications were screened, and their references were hand-searched to identify additional studies. Clinicaltrials.gov was also searched to identify ongoing or unpublished trials. The American Pediatric Surgical Association Outcomes and Clinical Trials Committee proposed six questions deemed pertinent to the surgical treatment of NEC. Recent Cochrane Reviews examined three of these topics; a literature review was performed to address the additional three specific questions., Results: The Cochrane Reviews support the use of prophylactic probiotics in preterm infants less than 2500 grams to reduce the incidence of NEC, as well as the use of human breast milk rather than formula when possible. There is no clear evidence to support delayed initiation or slow advancement of feeds. For surgical treatment of NEC with perforation, there is no clear support of peritoneal drainage versus laparotomy. Similarly, there is a lack of evidence comparing enterostomy versus primary anastomosis after resection at laparotomy. There are little data to determine the length of treatment with antibiotics to prevent recurrence of NEC., Conclusion: Based on available evidence, probiotics are advised to decrease the incidence of NEC, and human milk should be used when possible. The other reviewed questions are clinically relevant, but there is a lack of evidence-based data to support definitive recommendations. These areas of NEC treatment would benefit from future investigation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The aim of this study is to review the current evidence on the diagnosis and management of empyema. The American Pediatric Surgical Association Outcomes and Clinical Trials Committee compiled 8 questions to address. A comprehensive review was performed on each topic. Topics included the distinction between parapneumonic effusion and empyema, the optimal imaging modality in evaluating pleural space disease, when and how pleural fluid should be managed, the first treatment option and optimal timing in the management of empyema, the optimal chemical debridement agent for empyema, therapeutic options if chemical debridement fails, therapy for parenchymal abscess or necrotizing pneumonia and duration of antibiotic therapy after an intervention. The evidence was graded for each topic to provide grade of recommendation where appropriate., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Details of piriformis syndrome, including the proper diagnosis and most effective form of treatment, continue to be controversial. While the cause, diagnosis, and treatment of piriformis syndrome remain elusive, many studies have been conducted to investigate newly developed diagnostic techniques as well as various treatment options for piriformis-induced sciatica. Despite the quantity of literature, few studies have demonstrated statistically significant results that support one form of treatment over another. Thus, despite the evidence supporting the newer treatment methodologies for piriformis syndrome, research should continue. It is important not only to evaluate treatment outcomes based on associated pain relief, but also to investigate the functional and anatomical return that patients experience from these studied treatments in order to fully explore the most effective form of therapy for piriformis syndrome.

Tyrosine nitration is an important sequel of cellular signaling induced by reactive oxygen species. Cisplatin is an anti-neoplastic agent that damages the inner ear through reactive oxygen species and by the formation of DNA adducts. This study reveals a correlation between cisplatin-mediated hearing loss and nitroxidative modification of cochlear proteins and is the first to report nitration of Lmo4. Cisplatin induced a dose-dependent increase in hearing loss in Wistar rats. A 10-15-dB decrease in distortion product amplitude and massive loss of outer hair cells at the basal turn of the cochlea was observed 3 days post-treatment after a 16 mg/kg dose. Cisplatin induced nitration of cellular proteins within the organ of Corti, spiral ganglion, and stria vascularis, which are known targets of cisplatin ototoxicity. Nitration of a 76-kDa cochlear protein correlated with cisplatin dose. The nitrated protein was identified as Lmo4 (LIM domain only 4) by MALDI-TOF (matrix-assisted laser desorption/ionization time of flight) mass spectrometry and confirmed by reciprocal immunoprecipitation and immunoblotting. Co-localization of nitrotyrosine and Lmo4 was particularly high in outer hair cell nuclei after cisplatin treatment. Cochlear levels of Lmo4 were decreased in rats treated with cisplatin. In vitro studies supported the repression of Lmo4 in nitroxidative conditions and the induction of apoptosis upon repression of Lmo4. Inhibition of cochlear protein nitration prevented cisplatin-induced hearing loss. As Lmo4 is a transcriptional regulator that controls the choice between cell survival and cell death, these results support the hypothesis that nitration of Lmo4 influences cisplatin-induced ototoxicity.

Purpose: Retinoblastoma (RB), an intraocular tumor of childhood, is commonly associated with mutations in the RB1 gene. RB116 is a novel, early passage RB cell line that has not been previously characterized. In this study, we examined RB116 for the expression of RB1 and tested the hypothesis that RB116 cells would express stem cell markers as well as retinal progenitor cell markers. We compared RB116 cells with other well known RB cell lines, including Y79 and WERI-RB27., Methods: We evaluated expression of RB1 in RB116 cells by sequencing, multiplex ligation-dependent probe amplification, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), western immunoblot, and immunocytochemistry. Next, RB116 cells, along with Y79 and WERI-RB27 cells, were examined for expression of stem cell markers (ABCG2, Nanog, Oct3/4, ALDH1A1) and retinal progenitor markers (PAX6, CHX10) by quantitative immunocytochemistry. Immunocytochemical findings were accompanied by PCR analysis., Results: RB116 cells expressed RB1 at the mRNA and protein levels, with no mutations detected by either sequencing analysis, or gene dosage abnormalities detected by multiplex ligation-dependent probe amplification. The RB1 protein was immunoreactive in RB116 cells with an atypical perinuclear localization. RB116 cells also expressed stem cell markers, with 3%-5% of cells immunopositive for ABCG2, Oct3/4 and ALDH1A1, with at least 18% of cells immunoreactive to Nanog. These findings were confirmed by RT-PCR. Small percentages of RB116 cells also exhibited immunoreactivity to retinal progenitor markers PAX6 (9.8%) and CHX10 (1.2%). Expression of mRNAs for these markers was confirmed by qRT-PCR., Conclusions: RB116 cells demonstrate RB1 expression accompanied by atypical perinuclear localization. RB116 cells also express primitive stem cell and retinal progenitor cell markers. Further studies on the phenotypes of both RB1-positive and RB1-negative human RB cells may be important in assessing differentiation potential of these cells, as well as designing targeted differentiation therapies.

Proteomics is a key technique that is helping elucidate many complex biological processes. The analysis of plant-pathogen interactions using proteomics is complicated by the presence of the proteomes of two species, but is benefiting from the developing maturity and power of these techniques. More and more pathogen genomes are being sequenced, so fungal proteomics is reaching its full potential and remains the chosen technology to unravel the molecular pathways of pathogenicity and resistance. In this chapter, we suggest proteomic strategies that have proved successful on various plant-interacting fungal species. Several protein extraction methods are described. For adequate quantitative analyses of protein abundances, we recommend either separation using two-dimensional gel electrophoresis or labelling with isobaric tags followed by two-dimensional HPLC separation. Proteins of interest are then identified using mass spectrometry. Identified proteins can assist in refining genome annotations, otherwise known as proteogenomics.

Aberrant DNA methylation (DNAm) is a feature of most types of cancers. Genome-wide DNAm profiling has been performed successfully on tumor tissue DNA samples. However, the invasive procedure limits the utility of tumor tissue for epidemiological studies. While recent data indicate that cell-free circulating DNAm (cfDNAm) profiles reflect DNAm status in corresponding tumor tissues, no studies have examined the association of cfDNAm with cancer or precursors on a genome-wide scale. The objective of this pilot study was to evaluate the putative significance of genome-wide cfDNAm profiles in esophageal adenocarcinoma (EA) and Barrett esophagus (BE, EA precursor). We performed genome-wide DNAm profiling in EA tissue DNA (n = 8) and matched serum DNA (n = 8), in serum DNA of BE (n = 10), and in healthy controls (n = 10) using the Infinium HumanMethylation27 BeadChip that covers 27,578 CpG loci in 14,495 genes. We found that cfDNAm profiles were highly correlated to DNAm profiles in matched tumor tissue DNA (r = 0.92) in patients with EA. We selected the most differentially methylated loci to perform hierarchical clustering analysis. We found that 911 loci can discriminate perfectly between EA and control samples, 554 loci can separate EA from BE samples, and 46 loci can distinguish BE from control samples. These results suggest that genome-wide cfDNAm profiles are highly consistent with DNAm profiles detected in corresponding tumor tissues. Differential cfDNAm profiling may be a useful approach for the noninvasive screening of EA and EA premalignant lesions.

We identify a role for the GDI-like solubilizing factor (GSF) PDEδ in modulating signalling through Ras family G proteins by sustaining their dynamic distribution in cellular membranes. We show that the GDI-like pocket of PDEδ binds and solubilizes farnesylated Ras proteins, thereby enhancing their diffusion in the cytoplasm. This mechanism allows more effective trapping of depalmitoylated Ras proteins at the Golgi and polycationic Ras proteins at the plasma membrane to counter the entropic tendency to distribute these proteins over all intracellular membranes. Thus, PDEδ activity augments K/Hras signalling by enriching Ras at the plasma membrane; conversely, PDEδ down-modulation randomizes Ras distributions to all membranes in the cell and suppresses regulated signalling through wild-type Ras and also constitutive oncogenic Ras signalling in cancer cells. Our findings link the activity of PDEδ in determining Ras protein topography to Ras-dependent signalling.

Pediatric surgery is defined by the rare performance of complex operations in children. As a consequence, pediatric surgeons have difficulty identifying high-level evidence to help guide management decisions. The American Pediatric Surgical Association (APSA) Outcomes and Clinical Trials Committee is dedicated to helping our membership identify best practices and appropriate standards for clinical management of pediatric surgical diseases. Often, the best available evidence will be the opinions and experience of our membership, and therefore, quantifying this experience and opinion correctly is of critical importance. The APSA Outcomes and Clinical Trials Committee has therefore developed guidelines for survey development and administration for use by the APSA membership., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To report changes in perceived visual functioning after surgery for symptomatic cataract with preoperative corrected distance visual acuity [CDVA] of 0.4 logMAR or better (Snellen equivalent, 20/50) and to investigate the relationship between any observed changes and preoperative physical characteristics and psychophysical consequences of the lens opacity and any changes in psychophysical findings after the procedure., Methods: Eighty-five patients with cataract completed a validated questionnaire concerning functional vision satisfaction and a series of visual performance assessments before and 2 months after cataract surgery. The lens optical density and Lens Opacities Classification System III score of the cataract were recorded. Correlations between changes in the Rasch-analyzed questionnaire score and changes in visual performance after cataract surgery, as well as preoperative psychophysical measures, lens optical density, and Lens Opacities Classification System III score, were determined., Results: The mean (SD) questionnaire score improved from 2.15 (0.36) to 1.54 (0.41) (P < .001). The preoperative questionnaire score (r = -0.44), preoperative mesopic glare disability [GD] (at 1.5 cycles per degree [cpd] [r = 0.34] and 3.0 cpd [r = 0.27]), and preoperative photopic GD (at 1.5 cpd [r = 0.24] and 3.0 cpd [r = 0.30]) showed statistically significant correlations with perceived improvements in visual functioning after surgery (P < .05). Changes in perceived visual functioning correlated significantly with changes in mesopic GD (at 1.5 cpd [r = -0.43] and 3.0 cpd [r = -0.28]; P < .05) and photopic GD (at 1.5 cpd [r = -0.24] and 3.0 cpd [r = -0.39]; P < .05). Neither preoperative CDVA nor change in CDVA after surgery correlated significantly with perceived improvement in visual functioning after the procedure (P > .05 for both)., Conclusion: Psychophysical tests alternative to CDVA better represent improvements in self-reported visual functioning following removal of symptomatic nonadvanced cataract.

Purpose: To investigate whether psychophysical, morphological, and/or optical characteristics of symptomatic non-advanced cataract are complementary to, or more appropriate than, visual acuity (VA) for the purposes of recording visual data that reflect subjective visual difficulty in patients with cataract that exhibit relative sparing of high contrast acuity (0.4 logarithm of minimal angle of resolution (logMAR) scale or better)., Methods: Eighty-two patients with symptomatic non-advanced cataract and no other ocular pathology were asked to complete a validated questionnaire, and to perform a series of visual function assessments including: corrected distance VA (CDVA); photopic and mesopic contrast sensitivity; photopic and mesopic glare disability (GD); reading acuity and reading speed; stereoacuity; and retinal sensitivity. Optical and morphological characteristics of the cataract were evaluated by lens optical density and by the Lens Opacities Classification System III, respectively. Correlations between questionnaire score and each of these measures were calculated., Results: Statistically significant negative correlations were observed between the Rasch-scaled questionnaire score and mesopic GD (at 3 and 6 cycles per degree (cpd); r=-0.396 (P<0.01) and -0.451 (P<0.05), respectively) and between the Rasch-scaled questionnaire score and photopic GD (at 3 and 6 cpd; r=-0.328 (P<0.01) and -0.440 (P<0.01), respectively)., Conclusion: Symptomatic non-advanced cataract, in the presence of good CDVA, is associated with measurable subjective visual difficulty, best reflected in a decrease in mesopic and photopic GD (at medium spatial frequencies). CDVA does not reflect the patient's visual dissatisfaction in such cases.

Background: Bellevue Hospital Medical Center is a level 1 trauma center in New York and a major referral center for complex hand injuries and amputations. These injuries typically occur at the workplace and are thought to be highly litiginous in nature. This study was conducted to analyze the cases involving hand surgery litigation related to trauma over the last 8 years at this institution., Methods: The authors performed a retrospective chart review of all claims filed against Bellevue Hospital Medical Center after treatment for a hand injury during 2001 to 2009. Twenty-three patients in total were identified and reviewed for age, mechanism/type of injury, complications, decision to replant, average time after injury to post claim, and whether settlement was obtained., Results: One of 23 patients who filed suit against Bellevue Hospital Medical Center received a successful settlement involving an incident surrounding the loss of a nonreplantable part. Of 168 patients in whom 219 replantations/revascularizations were performed, five patients filed claims, all surrounding a failed attempt. In total, there were seven complications: five failed replants, one failed thenar flap, and one patient who needed a revision completion amputation., Conclusions: The majority of the patients who filed claims did so because of the decision not to replant. Only 2.98 percent (five of 168) of all attempted revascularization/replantation patients filed claims against the authors' institution; all claims were notably dropped. The legal system appears to support physicians and institutions that treat these complex injuries. Better patient understanding of the decision-making process and complications involving treatment of traumatic hand injuries may decrease the number of future lawsuits.

The provision of quality mental health services in rural areas continues to be an ongoing challenge for nurses and the patients they serve. The use of computer mediated communication to construct collaborative learning environments similar to those suggested in Wenger's community of practice framework has the potential to mitigate a number of the difficulties faced by rural health care providers. The author presents a brief discussion of social learning theories, the communities of practice framework, and related concepts. Examples of current online communities of practice used as a means for knowledge construction in various professional disciplines are presented in building the case for the fit between online communities of practice and the needs of nurses in rural mental health. Nurses providing mental health care in rural areas have documented needs for interdisciplinary teamwork, access to a collaborative learning environment, and ongoing contact with expert resources. The construction of online communities of practice could potentially address a multitude of concerns identified by nurses practicing mental health care in rural areas.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder, typically presenting in the second and third decade. We report the case of an elderly gentleman with significant vascular risk factors, presenting with slowly progressive, bilateral, visual loss with high signal lesions in the pericallosal and periventricular deep white matter on MRI brain studies. Possible diagnoses included late-onset MS, ischaemic optic neuropathies, a mitochondrial disorder or an overlap syndrome such as Harding's disease.

Purpose: To quantify the effect on refractive outcomes after cataract surgery of personalization of Haigis intraocular lens (IOL) constants for a given surgeon-IOL combination., Setting: Institute of Eye Surgery and Institute of Vision Research, Whitfield Clinic, Butlerstown North, Waterford, Ireland., Methods: Personalization of Haigis IOL constants was performed using a series of 248 suitable eyes after biometry by partial coherence interferometry (IOLMaster) and IOL prediction based on optimized IOL constants derived from pooled data from the User Group for Laser Interference Biometry web site. A mean error of prediction and a mean absolute error were then calculated using the personalized IOL constants and compared with those derived using optimized IOL constants, allowing evaluation and quantification of the maximum realizable refractive benefits (if any) of personalization., Results: There was no statistically significant difference between personalized and optimized Haigis IOL constants in absolute error or the proportion of eyes within +/-1.00 diopters (D), +/-0.50 D, or +/-0.25 D of the target postoperative refraction in all eyes, short eyes (axial length [AL] <22 mm; n = 19), average eyes (AL > or =22 mm and <24.5 mm; n = 149), or long eyes (AL >24.5 mm; n = 46) (all P>.05, McNemar test). Ten eyes with a short AL had a smaller absolute error (by > or =0.30 D) in association with personalized IOL constants., Conclusion: Personalized Haigis IOL constants showed marginal, but statistically nonsignificant, refractive advantages over optimized Haigis IOL constants, but only in eyes with a short AL. FINANCIAL DISCLAIMER: No author has a financial or proprietary interest in any material or method mentioned., (Copyright 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

The synthesis of two asymmetric dinuclear complexes with the formula [M(bpy)(2)(bpt)Ru(tpy)Cl](2+), where M = Ru (1a), Os(2a); bpy = 2,2'-bipyridyl; Hbpt = 3,5-bis(pyridin-2-yl)1,2,4-triazole and tpy = 2,2',6',2''-terpyridine, is reported. The compounds obtained are characterized by mass spectrometry, (1)H NMR, UV/vis/NIR absorption, luminescence, and resonance Raman spectroscopy. Deuterium isotope labeling facilitates assignment of the (1)H NMR and resonance Raman spectra. The interaction between the two metal centers, mediated by the bridging 1,2,4-triazolato moiety in the mixed valent state, is assigned as type II based on the observation of metal to metal charge transfer absorption bands at 7090 and 5990 cm(-1) for 1a and 2a, respectively. The extent of localization of the emissive excited state was determined by transient resonance Raman and emission spectroscopy. Both 1a and 2a show phosphorescence at the same wavelengths; however, whereas for compound 1a the emission is based on the Ru(tpy)Cl- center, for 2a the emissive state is localized on the Os(bpy)(2)- unit. This indicates that also in the excited state there is efficient interaction between the two metal centers.

Age-related macular degeneration (AMD) is the most common form of visual impairment, in people over 65, in the Western world. AMD is a multifactorial disease with genetic and environmental factors influencing disease progression. Cigarette smoking is the most significant environmental influence with an estimated increase in risk of 2- to 4-fold. Smoke-induced damage in AMD is mediated through direct oxidation, depletion of antioxidant protection, immune system activation and atherosclerotic vascular changes. Moreover, cigarette smoke induces angiogenesis promoting choroidal neovascularisation and progression to neovascular AMD. Further investigation into the effects of cigarette smoke through in vitro and in vivo experimentation will provide a greater insight into the pathogenesis of age-related macular degeneration.

A series of binuclear ruthenium and osmium complexes [(bipy)(2)Ru(qpy)Ru(bipy)(2)](4+) (1), [(bipy)(2)Os(qpy)Os(bipy)(2)](4+) (2), [(bipy)(2)Ru(pytr-bipy)Ru(bipy)(2)](3+) (3), [(bipy)(2)Ru(pytr-bipy)Os(bipy)(2)](3+) (4), [(bipy)(2)Os(pytr-bipy)Ru(bipy)(2)](3+)(5) and [(bipy)(2)Os(bpbt)Os(bipy)(2)](2+) (6) {bipy = 2,2'-bipyridyl; qpy = 2,2':5',5'':2'',2'''-quaterpyridyl; pytr-bipy = 3-(2,2'-bipyrid-6-yl)-5-(pyrid-2-yl)-1,2,4-triazolato, and bpbt = 5,5'-bis-(pyrid-2''-yl)-3,3'-bis-1,2,4-triazolato} are reported. Analysis of the electrochemical data focuses on structural factors and on determining the extent of electronic communication between the metal centres in the mixed valence oxidation state. Intervalence charge transfer (IT) bands could be identified in the spectra of the complexes 4 and 6 only. Analysis of their spectroelectrochemical data leads to the conclusion that the IT is superexchange mediated through the HOMO of the bridging ligand.

The synthesis and characterisation of a series of dinuclear ruthenium and osmium polypyridyl metal complexes based on the bridging ligands [5-(5'-bipyridin-2',2''-yl)-3-(pyridin-2-yl)]-1,2,4-triazole (Hpytr-bipy), 2,2'-bis(pyridin-2''yl)-5,5'-bis(pyridin-3''-yl) (bipy-bipy) and 5,5'-bis(pyridin-2''-yl)-3,3'-bis(1,2,4-triazole) (Hpytr-Hpytr) are reported. The dinuclear complexes have been synthesised via a Ni(0) catalysed cross-coupling reaction from brominated precursors. With this approach a mixture of three products is obtained, which are separated by chromatographic methods. The compounds obtained are characterised by elemental analysis, (1)H NMR, absorption and emission spectroscopy. The synthetic approach developed offers a new route to asymmetric multinuclear supramolecular structures that is complimentary to the complexes as ligands/complexes as metal approaches.

Aim: To evaluate the roles of plain X-ray and computed tomography (CT) orbital imaging in cases and suspected cases of intraocular foreign body (IOFB)., Methods: Retrospective review of clinical and radiological data relating to 204 consecutive cases and suspected cases of IOFB.SettingRoyal Victoria Eye and Ear Hospital, Dublin, Ireland., Results: Plain X-rays were performed in the absence of clinically evident ocular penetration in 177 (87%) cases, and no IOFB was demonstrated in any of these radiographs. Twenty-seven (13%) plain X-ray radiographs were obtained in the presence of clinically evident ocular penetration, and an IOFB was clinically visible in 19 (70%) of these cases. CT scans were undertaken in 21 (10%) of the 204 patients. Of these CT images, 9 (43%) and 12 (57%) were undertaken in the absence and presence of clinically evident ocular penetration, respectively. None (0%) and all (100%) of the CT scans obtained in the absence and presence of clinically evident ocular penetration demonstrated an IOFB, respectively., Conclusion: Plain X-ray and CT orbital imaging are non-contributory in the absence of clinically evident ocular penetration. In the presence of clinically evident ocular penetration, and where an IOFB is clinically visible, plain X-ray orbital radiography may have a role in excluding multiple IOFBs. In the presence of clinically evident ocular penetration, but where an IOFB is not clinically visible, CT orbital imaging remains the investigation of choice, and the role of pre-CT plain X-ray orbital radiography, as recommended by the guidelines of the Royal College of Radiologists, merits re-evaluation.

Aims: Experience with anti-tumour necrosis factor alpha medications in ophthalmology has been mainly in the treatment of resistant uveitis and scleritis. There have been a few case reports and one case series detailing the use of infliximab in the treatment of orbital inflammatory disease, but there is still limited experience with these agents in a variety of orbital inflammatory conditions. We describe successful suppression of inflammation with infliximab in the Idiopathic orbital inflammation, thyroid associated orbital inflammation and chronic relapsing inflammatory optic neuropathy., Methods: This is a retrospective observational case series of five cases of orbital and ocular inflammation., Results: We describe effects of infliximab in the treatment of three cases of orbital inflammation and two cases of chronic relapsing inflammatory optic neuropathy, all of which were unresponsive to alternative immune modulators. The patients received relief of symptoms and signs of inflammation in all five cases. However, this relief was not absolute as symptoms returned around week 5 post-inflammation., Conclusion: This report highlights the expanding role of the biological agents in ophthalmology. Although not the answer in treatment, they offer a valuable alternative to steroids in cases of refractory inflammation.

Aims: To investigate the role of the major histocompatibility complex in Irish patients with optic neuritis (ON) and determine whether HLA-DRB1 genotypes are a risk factor for the development of multiple sclerosis (MS) in such patients., Method: All patients were Caucasian, had Irish ancestry and had MRI of brain and optic nerves within 2-3 weeks of presentation. Patients were referred to a neurologist if MRI findings were consistent with a diagnosis of MS. HLA-DRB1 allele and phenotype frequencies for 78 patients with a clinical diagnosis of acute ON were compared with those for 250 healthy bone marrow donors., Results: An ON/MS positive patient was 3.4 times more likely than an ON/MS negative patient to be DRB1*15 positive. No difference in age profile was detected between ON/MS positive and ON/MS negative patients or between the ON male and female subgroups. No gender or HLA-DRB1 association was identified for ON/MS negative patients. Female gender was significantly increased among ON/MS positive patients with a p value of 0.0053., Conclusions: DRB1*15 is a significant predisposing factor for ON. This ON patient cohort has also provided an opportunity to evaluate the relationship of HLA genotype with the risk of MS development. The findings of this study indicate that Irish individuals presenting with ON and who are HLA DRB1*15 positive have a higher risk than HLA DRB1*15 negative patients of presenting with MRI findings indicative of MS. This study has also demonstrated that female gender is a risk factor for developing MS in the Irish population.

The effects of rigor temperature and electrical stimulation on venison quality were assessed using venison longissimus dorsi muscle. In the first trial, effect of rigor temperature (0, 15, 25, 30, 35 and 42°C) and time post-mortem (at rigor, 3, 7 and 14 days) on drip and cooking losses, % expressible water (water holding capacity, WHC), sarcomere length, protein solubility, meat tenderness and colour were investigated. In the second trial, the effects of rigor temperature (15 and 35°C), electric stimulation (stimulated or not stimulated) and time (at rigor, 3 and 6 weeks post-mortem) on tenderness and colour were further investigated. Results of the first trial showed no clearly established trends of the effect of rigor temperature and time on the cooking and drip losses and protein solubility except venison muscles that went into rigor at 42°C tended to have higher drip loss and lower protein solubilities compared to muscles that went into rigor at the other temperatures. Venison water holding capacity (WHC) decreased with the increase in rigor temperature (P<0.001) and venison became more tender with time post-mortem. Venison colour improved with increasing rigor temperature. During display, samples that went into rigor at 15, 25 and 35°C had the lowest and those at 0 and 42°C had the highest rate of change of redness (a(∗)) value with time. In the second trial, tenderness was improved by stimulation (P=0.01). Redness (a(∗)) values were affected by rigor temperature (P<0.01) and post-mortem time (P<0.001) but not by electrical stimulation. It is concluded that venison tenderness can be improved via the manipulation of rigor temperature to obtain acceptable level of tenderness early post-mortem with less damaging effect on colour stability.

We present a density functional theory (DFT) study of an osmium polypyridyl complex adsorbed on Au(111). The osmium polypyridyl complex [Os(bpy)2(P0P)Cl]n+ [bpy is 2,2'-bipyridine, P0P is 4,4'-bipyridine, n = 1 for osmium(II), and n = 2 for osmium(III)] is bound to the surface through the free nitrogen of the P0P ligand. The calculations illuminate electronic properties relevant to recent comprehensive characterization of this class of osmium complexes by electrochemistry and electrochemical scanning tunneling microscopy. The optimized structures for the compounds are in close agreement with crystallographic structures reported in the literature. Oxidation of the complex has little effect on these structural features, but there is a substantial reordering of the electronic energy levels with corresponding changes in the electron density. Significantly, the highest occupied molecular orbital shifts from the metal center to the P0P ligand. The surface is modeled by a cluster of 28 gold atoms and gives a good description of the effect of immobilization on the electronic properties of the complexes. The results show that the coupling between the immobilized complex and the gold surface involves electronic polarization at the adsorbate/substrate interface rather than the formation of a covalent bond. However, the cluster is too small to fully represent bulk gold with the result that, contrary to what is experimentally observed, the DFT calculation predicts that the gold surface is more easily oxidized than the osmium(II) complex.

The accumulation of metmyoglobin (MetMb) at the surface of meat during storage contributes significantly to its discolouration. Under appropriate conditions it may be possible to utilise residual meat MetMb reducing activity to maintain fresh colour. Venison meat colour stability is poorer compared with other species. Hence, we evaluated the capacity of completely discoloured venison (n=12 animals) to reduce MetMb under anaerobic conditions in order to decipher more clearly the role MetMb reducing activity may play. The reducing capacity of venison (1 day, 3, and 6 weeks post-mortem), electrical stimulation, surface location (top and bottom) and rigor temperature (15 and 35°C) on MetMb were evaluated. Surface MetMb decreased (P<0.001) during storage while deoxymyoglobin increased (P<0.001) demonstrating MetMb reduction. Metmyoglobin reduction was greater (P<0.001) in venison which entered rigor at 15°C, the reduction at the bottom surface of the steaks was greater (P<0.001) compared with the top surface, and electrical stimulation had no affect (P>0.05). These data demonstrate that metmyoglobin reducing activity occurs anaerobically in completely discoloured venison following storage display. The practical application for this finding needs to be determined.

Background: Statewide trauma registries have proliferated in the last decade, suggesting that information could be aggregated to provide an accurate depiction of serious injury in the United States., Objectives: To determine whether variability exists in the composition and content of statewide trauma registries, specifically addressing case-acquisition, case-definition (inclusion criteria), and registry-coding conventions., Methods: A cross-sectional, two-part survey was administered to managers of all statewide trauma registries. State trauma registrars also provided inclusion and exclusion criteria from their state registry and abstracted a clinical vignette designed to identify coding inconsistencies., Results: Thirty-two states maintain a centralized registry, but requirements for data submission vary significantly. Inclusion and exclusion criteria also vary, particularly for nontraumatic injuries. Coding conventions adopted by states for vague or missing information are dissimilar. When abstractions of the clinical vignette are compared, only 19% and 47% of states provided similar quantity or content for injury e-coding and diagnostic coding, respectively. Injury severity scores (based on diagnostic coding) demonstrated a range from 2 to 18., Conclusions: Statewide trauma registries are prevalent but vary significantly in composition and content. Standardizing inclusion criteria, variable definitions, and coding conventions would greatly enhance the usability of an aggregated, national trauma registry.

Background: Current dogma suggests that the diagnosis of rectal injury can be made after physical examination and proctoscopy (PR). However, anecdotal evidence suggests that these modalities lack specificity when applied to children and that computed tomography (CT) scanning may be superior. A direct comparison between CT scanning and PR has not been performed. We therefore sought to compare CT with PR in the diagnosis of rectal injury by analyzing our large institutional experience., Methods: To assess institutional outcome, the charts of all children younger than 18 years admitted to our level I trauma center (1999-2004) were prospectively collected and retrospectively assessed. Demographics, diagnostic accuracy (PR vs CT), and outcome (length of stay, days in the intensive care unit [ICU], Injury Severity Score, and missed injury) were assessed., Results: There were 24 injuries (63% boys, 71% blunt, 100% survival), and diagnostic modality included the following: PR, 37.5%; CT, 37.5%; laparotomy alone, 8%. Length of stay (PR 5.7 +/- 6.2 vs CT 13.7 +/- 22.2, NS) were similar between groups. Of the missed rectal injuries, 66% of patients undergoing PR had missed injuries that were ultimately detected by CT whereas 33% of the patients undergoing CT scan had a missed injury., Conclusion: CT is at least as accurate as PR in diagnosing pediatric rectal injury. Consideration of early scanning as opposed to PR may improve diagnosis and outcome in these patients.

The underlying concepts for calculating the power of a statistical test elude most investigators. Understanding them helps to know how the various factors contributing to statistical power factor into study design when calculating the required number of subjects to enter into a study. Most journals and funding agencies now require a justification for the number of subjects enrolled into a study and investigators must present the principals of powers calculations used to justify these numbers. For these reasons, knowing how statistical power is determined is essential for researchers in the modern era. The number of subjects required for study entry, depends on the following four concepts: 1) The magnitude of the hypothesized effect (i.e., how far apart the two sample means are expected to differ by); 2) the underlying variability of the outcomes measured (standard deviation); 3) the level of significance desired (e.g., alpha = 0.05); 4) the amount of power desired (typically 0.8). If the sample standard deviations are small or the means are expected to be very different then smaller numbers of subjects are required to ensure avoidance of type 1 and 2 errors. This review provides the derivation of the sample size equation for continuous variables when the statistical analysis will be the Student's t-test. We also provide graphical illustrations of how and why these equations are derived.

Purpose: Controversy exists regarding the criteria for placement of infants on extracorporeal membrane oxygenation (ECMO) at low birth weights. The authors hypothesized that ECMO is effective and safe in babies under 2 kg and sought to examine outcome and survival rate in these infants., Methods: All patients less than 30 days old in the Extracorporeal Life Support Organization (ELSO) registry (n = 14,305) were divided into those less than 2 kg (n = 663) and more than 2 kg (n = 13,642). Multiple regression analysis determined factors that predicted survival rate and the lowest safe weight for ECMO., Results: Overall survival rate was 76% and was lower in infants less than 2 kg (> or =2 kg, 77% v <2 kg, 53%, P <.0001). Survival rate was significantly lower for patients with diaphragmatic hernia (CDH), bleeding, and intracranial hemorrhage (ICH) by regression. The incidence of ICH in babies less than 2.0 kg was 6% versus 4% in those more than 2.0 kg (P <.05). Regression analysis determined that the lowest weight at which a survival rate of 40% could be achieved was 1.6 kg., Conclusions: Cannulation for ECMO may be safe and effective in babies under 2.0 kg and potentially as low as 1.6 kg. Judicious anticoagulation might limit bleeding, which occurred in a minority of these patients.

Purpose: Controversy persists regarding the factors influencing survival in patients with congenital diaphragmatic hernia (CDH), in particular, the role of timing of surgery. The authors therefore sought to determine such factors and to assess the relative role of timing of surgery on outcome., Methods: All CDH newborns 1991 through 2002 (n = 111) were divided into those undergoing repair before ("early" n = 35), or after ("late" n = 76) 48 hours. A multivariate analysis was performed to determine the relative impact of various factors on survival rate., Results: Overall survival rate was 64%. There was no effect on survival of heart rate, temperature, systolic blood pressure, age, extracorporeal membrane oxygenation use, mesh use, infections, or intracranial hemorrhage, and there was no difference between early (68%) or late (62%) repair (P =.2). Initial pCO2 greater than 50, pO2 less than 40, cardiac defects, or renal failure significantly decreased survival rate., Conclusions: Significant factors influencing survival rate in patients with CDH include cardiac defects, renal failure, and the initial blood gases and not the timing of surgery. CDH repair should be based on the optimization of clinical parameters as opposed to a specific time period to improve outcome.

Using a perceptual technique it is shown that patients with chronic external ophthalmoplegia have shortened vestibular responses. It is postulated that this is secondary to the retinal image slip experienced by these patients during head movements and a useful compensatory mechanism to suppress motion-induced sickness and spatial disorientation.