Hydrophosphination using [GeCl{N(SiMe3)2}3] as a pre-catalyst.

Transformations catalyzed by germanium are scarce, with examples mainly limited to widely catalyzed processes such as polymerisation of lactide and hydroboration of carbonyls. Reported is the first example of hydrophosphination using a germanium pre-catalyst, yielding anti-Markovnikov products when diphenylphosphine is reacted with styrenes or internal alkynes at room temperature.

Peer Relationship Experiences Of Deaf And Hard-Of-Hearing Adolescents.

Deaf and hard-of-hearing adolescents (DHH) experience more peer problems and lower levels of friendships than their hearing peers. This study used a qualitative approach to identify their experiences of peer problems and factors influencing them. A sample of 30, 13-19 year-old DHH adolescents with a moderate to profound hearing loss, drawn from a population-based cohort study in which their receptive language and social-emotional skills had been assessed, underwent semi-structured interviews. Interviews were analyzed using thematic analysis. Participants reported that, overall, they had developed positive and rewarding relationships with their peers, notwithstanding their earlier experience of being bullied. Conflicts and infrequency of interaction in their friendships were mainly reported by girls. Adolescents with moderate hearing loss were identified as facing the same or even more barriers than adolescents with severe to profound hearing loss in making new friends. Implications for educational practice are discussed.

Benign Intracranial Hypertension Necessitating Ventriculoperitoneal Shunt Insertion Secondary to Growth Hormone Therapy

Presentation Constant bilateral frontal headache associated with early morning awakenings, two episodes of vomiting and blurred vision. Diagnosis Benign Intracranial Hypertension. Treatment Repeat Lumbar Punctures were performed. GH was stopped and acetazolamide commenced. Later requiring VP shunt due to refractory symptoms with full resolution of symptoms. Conclusion Surgical management involving shunt procedures are reserved for refractory cases and are highly effective at resolving intractable symptoms.

1,1-Diphosphines and divinylphosphines via base catalyzed hydrophosphination.

A catalytic hydrophosphination route to 1,1-diphosphines is yet to be reported: these narrow bite angle pro-ligands have been used to great effect as ligands in homogeneous catalysis. We herein demonstrate that terminal alkynes readily undergo double hydrophosphination with HPPh2 and catalytic potassium hexamethyldisilazane (KHMDS) to generate 1,1-diphosphines. A change to H2PPh leads to the formation of P,P-divinyl phosphines.

An assessment of Irish farmers' knowledge of the risk of spread of infection from animals to humans and their transmission prevention practices.

The aim of this study was to ascertain farmers' knowledge of the risk of spread of infection from animals to humans, and their transmission prevention practices. This was a survey of farmers who submitted material to Ireland's Regional Veterinary Laboratories in 2015. There was an 84% response rate (1044 farmers). Ninety per cent of farmers were not aware that infection can be acquired from apparently healthy animals. Over half were not aware that disease could be contracted from sick poultry or pets. Conversely, the knowledge of the risk to pregnant women of infection from birthing animals was high (88%). Four-fifths of farmers sourced drinking water from a private well, and of these, 62% tested their water less frequently than once a year. Of dairy farmers, 39% drank unpasteurised milk once a week or more frequently. Veterinarians were the most commonly cited information source for diseases on farms. The survey findings indicate that the level of farmers' knowledge and awareness of the spread of infection from animals to humans is a concern. Further education of the farming community is needed to increase awareness of both the potential biohazards present on farms and the practical measures that can be taken to mitigate the risk of zoonoses.

Waterborne outbreak of cryptosporidiosis in the South East of Ireland: weighing up the evidence.

BACKGROUND: In late Spring 2012, 12 cases of cryptosporidiosis in a town in the South East of Ireland were notified to the regional Department of Public Health. AIM: The purpose of this paper is to describe the outbreak and the investigative process which led to the conclusion that the source was a public drinking water supply. METHODS: Outbreak and incident control teams were convened to investigate and control the outbreak. RESULTS: Eleven cases were speciated as Cryptosporidium parvum. GP60 analysis demonstrated that 10 were C. parvum IIaA20G3R1, indicating that the cases were linked. The public water supply was the only common risk factor identified. Increased water sampling identified Cryptosporidium muris/andersoni in the treated water at one of two water treatment plants (Water Treatment Plant, WTP A) for the supply, and on the network. C. parvum was subsequently identified in raw water from WTP A. CONCLUSIONS: The Health Service Executive (HSE) concluded that this outbreak was "probably associated with water" produced at WTP A based on (1) descriptive epidemiological evidence suggesting water-related illness and excluding other obvious explanations; and (2) water treatment failure at WTP A. WTP A was closed to facilitate an upgrade. No boil water notice was required as a supplementary supply was available. The upgrade was completed and the incident closed in 2013.

Aminopiperidine based complexes for lactide polymerisation.

Herein we report the synthesis and characterisation of a series of salalen and salan ligands derived from 2-(aminomethyl)piperidine. Depending on the choice of starting salicylaldehyde, a bicyclic salan type ligand (1-3H2) or imino salalen type ligand (4-6H, 7-9H2) were prepared. The ligands were successfully complexed to group 4 metals and aluminium; with hafnium and zirconium octahedral complexes, M(1-3)2, were realised; whilst with aluminium tetrahedral and trigonal bipyramidal complexes, Al(1-9)Mex (x = 1,2), were isolated. The complexes have been characterised in solution via(1)H and (13)C{(1)H} NMR spectroscopy and in the solid state by X-ray crystallography. The group 4 complexes were observed to have a fac-fac arrangement of ligands and there were two isomers present when 3H2 was ligated. The imino aluminium complexes Al(7-9)Me were isolated as a mixture of diastereoisomers. The resultant complexes were trialed in the ring opening polymerisation of rac-lactide with both heterotactic and isotactic PLA being demonstrated. Tacticity was found to be dependent on the nature of the ligand and metal used; the M(1-3)2 complexes were generally found to have a heterotactic preference (Pr = 0.67-0.76) and the aluminium polymerisation outcome was dictated more by the steric influence of the ligand, particularly for Al(4/6)Me2/Al(7/9)Me.

Copper malonamide complexes and their use in azide-alkyne cycloaddition reactions.

We report a rare example of the malonamide functionality being used as a ligand in copper catalysis. We have ligated a homologous series of these O,O-chelating architectures to copper, investigated their structure and exploited them in azide-alkyne cycloaddition reactions for the step-growth synthesis of oligo(triazoles) and in the synthesis of small organic azoles.

Bone protection and anti-epileptic drugs: the effect of audit and computer messaging on supplementation prescribing practices.

OBJECTIVE: This audit assessed the impact of individualised written recommendations and a computer message, on repeat prescriptions for calcium and vitamin D supplements, for patients on long term AEDs. METHODS: 1041 adult patients with epilepsy were retrospectively followed from 2004, from the time of the introduction of the Quality and Outcomes Framework (QOF) and the publication of the National Institute of Clinical Evidence (NICE) guidelines for epilepsy, up until 2011. In 2009 a clinical notes review of 414 of the above patients, in Ellesmere Port and Neston (13 practices) was performed, suggesting supplementation, where appropriate, in a written report. A computer message was added to relevant prescriptions also recommending supplements, in the above practices plus all 26 practices in Chester and the surrounding area. The number of patients receiving repeat prescription for supplements in each area between 2004 and 2011 was analysed. RESULTS: There was a significant increase in the repeat prescriptions of supplements in 2010/11 after the interventions, the increase being most marked in Ellesmere Port and Neston where both written recommendations and computer message had occurred compared with the two areas with the computer message only. CONCLUSION: Quality audit with written recommendations, and a message added to the General Practice (GP) computer systems significantly increased the number of repeat prescriptions of calcium and vitamin D supplements in this group of patients. PRACTICE IMPLICATIONS: Where clear guidelines are established, this study demonstrates that continuing education and counselling of GPs and use of computer messaging would result in improved compliance with such guidelines.

The parathyroid hormone receptorsome and the potential for therapeutic intervention.

The parathyroid hormone 1 receptor (PTH1R) is activated by parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP), hormones that mediate mineral ion homeostasis and tissue development, respectively. These diverse actions mediated by one receptor are likely due to the formation of cell-specific receptorsome complexes with cytosolic constituents. Through the second and third intracellular loops, the PTH1R couples to several G protein subclasses, including Gs, Gq/11, Gi/o and G12/13, resulting in the activation of many pathways. The PTH1R carboxy-terminal tail directs interactions with a plethora of binding partners. The WD1 and WD7 repeats of the G protein ß subunit directly bind to a novel interaction domain located near the amino-terminal end of the PTH1R carboxy-terminal tail. This Gßγ binding site likely contributes to the promiscuous G protein coupling displayed by the PTH1R. Partially overlapping this site is an EF-hand binding domain that directs interactions with calpain, a calcium-activated protease, and calmodulin, a ubiquitous calcium sensor. A lysine-arginine-lysine motif located on the juxtamembrane region of the carboxy-terminal tail mediates interactions with ezrin, an actin-membrane cross-linking protein. The C-terminus of the PTH1R binds to the sodium-hydrogen regulatory factors (NHERFs) via a PDZ domain-mediated interaction, an association that influences signaling and membrane anchoring. Through direct interactions with ezrin and NHERF-1, a PTH1R receptorsome complex exists on apical membranes of the proximal tubule, an assembly that directs PTH-mediated regulation of phosphate transport. Targeting the PTH1R receptorsome will likely enhance therapies directed towards the treatment of osteoporosis and enhancing the hematopoietic stem cell niche.

Cochlear-implanted children from homes where English is an additional language: findings from a recent audit in one London centre.

A 5-year retrospective audit of demographic, audiological, and other records of 147 children implanted at one London centre was conducted. The aim was to detail the number of children implanted, with a specific focus on children from families with English as an additional language (EAL), and to compare these children with children from monolingual English-speaking families on a variety of characteristics known to affect paediatric cochlear implant outcomes. In all, 28% of children were from families where English is an additional language, with 15 different languages recorded. There were no differences between EAL and English-speaking children with respect to age of implantation; bilateral versus unilateral implants or hearing levels in better ear. There were differences between these groups in aetiology, in the occurrence of additional needs, and in educational placements. Information about speech and language outcomes was difficult to gather. Conclusions indicate the need for more detailed record-keeping especially about children's home languages for purposes of planning intervention and for the inclusion of children with EAL in future studies.

The rate of horizontal transmission of antibiotic resistance plasmids is increased in food preservation-stressed bacteria.

AIM: The aim of this study was to investigate the possibility that sublethal food preservation stresses (high/low temperature, osmotic and pH stress) can alter the rate of horizontal transmission of antibiotic resistance (ABR) plasmids between Escherichia coli strains and between E. coli and Salmonella serotype Typhimurium. METHODS AND RESULTS: Escherichia coli donor cultures, carrying F1 plasmid R386 and Inc I1 plasmid TP307 and E. coli and Salm. Typhimurium recipient cultures were prestressed under a range of sublethal environmental conditions (high/low temperature, osmotic and pH stress). The prestressed donor and recipient cultures were then mated and the transmission rate calculated. The study found that the horizontal transmission rate of plasmids R386 and TP307 was significantly increased (P < 0.05) when prestressed donor and recipient cells are mated under conditions of environmental stress. CONCLUSION: The results from this study indicate that, the sublethal stresses that food pathogens encounter in modern food preservation systems increase the inter- and intra-specific horizontal transmission of selected ABR plasmids. SIGNIFICANCE AND IMPACT OF THE STUDY: Increased use of bacteriostatic (sublethal), rather than bacteriocidal (lethal) food preservation systems, may be contributing to the dissemination of ABR among important food borne pathogens.

A comparison of breast muscle characteristics in three broiler great-grandparent lines.

Genetic selection of broiler chickens has led to a gross overdevelopment of the broiler breast muscle pectoralis major. This may have resulted in increased myopathy and detrimental effects on meat quality. The present study examined 3 commercial great-grandparent lines (lines A, B, and C). Lines A and B are female lines, and line C is a male line. The mean BW of line C (2.7 kg) was significantly greater than those of lines A and B (both 2.3 kg). However, the mean breast yield of both lines B and C (8.9 and 8.7%, respectively) was significantly greater than that of line A (6.9%). Line B therefore matched the meat yield of line A while maintaining a high reproductive capacity. The mean breast fillet weight of line A (169 g) was significantly lower than lines B (207 g) and C (235 g). No differences were observed between lines in either mean fiber size or amount of connective tissue. Therefore, additional fibers must provide the additional weight in the breast fillet of lines B and C, compared with A. Plasma creatine kinase activity, a commonly used marker of muscle damage, was significantly higher in line A (1368 IU/L) than in lines B (995 IU/L) and C (982 IU/L). However, qualitative evaluations of muscle pathology revealed no differences among lines. Selection for increased embryonic muscle fiber number, rather than for increased radial fiber growth, could improve growth potential and may also alleviate muscle damage.

Skeletal muscle fibre growth and growth associated myopathy in the domestic chicken (Gallus domesticus).

1. Genetic selection of broilers may have pushed muscle fibres to their maximum functional size constraints. Broiler (B), female great-grandparent (GGP) and layer (L) lines were weighed, blood sampled and killed from 5 to 25 weeks of age. 2. At 25 weeks, Pectoralis major (Pm) fibre size reached by the B (65.9 microm) and GGP (59.8 microm) were 1.5 times greater than the L (38.1 microm). In the B and GGP lines, fibre growth of the Pm markedly exceeded that of the Biceps femoris (Bf) muscle. However, in the L line, fibre growth of the Pm and Bf muscle was comparable. Connective tissue content was generally higher in the Bf than in the Pm of all lines. 3. Centralised nuclei were observed predominantly in Pm, and may regulate fibre size. Both large muscle fibres and inadequate capillary supply may induce metabolic stress in B and GGP lines due to the large diffusion distances for oxygen, metabolites and waste products. 4. Enzyme markers of muscle damage (creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransaminase (AST)) and histopathological analysis of Pm and Bf indicated greater myopathy in B and GGP vs L. 5. Regenerative processes were associated with oestrogen secretion. Reduced CK and LDH preceded egg yolk precursor production and increased calcium uptake for eggshell synthesis in all three lines. Oestrogen may stimulate muscle fibre regeneration and recovery as a myo-protective adaptation to potentially detrimental changes in calcium economy during egg production.

Role of calcium channels in carboxyl-terminal parathyroid hormone receptor signaling.

Parathyroid hormone (PTH), an 84-amino acid polypeptide, is a major systemic regulator of calcium homeostasis that activates PTH/PTHrP receptors (PTH1Rs) on target cells. Carboxyl fragments of PTH (CPTH), secreted by the parathyroids or generated by PTH proteolysis in the liver, circulate in blood at concentrations much higher than intact PTH-(1-84) but cannot activate PTH1Rs. Receptors specific for CPTH fragments (CPTHRs), distinct from PTH1Rs, are expressed by bone cells, especially osteocytes. Activation of CPTHRs was previously reported to modify intracellular calcium within chondrocytes. To further investigate the mechanism of action of CPTHRs in osteocytes, cytosolic free calcium concentration ([Ca(2+)](i)) was measured in the PTH1R-null osteocytic cell line OC59, which expresses abundant CPTHRs but no PTH1Rs. [Ca(2+)](i) was assessed by single-cell ratiometric microfluorimetry in fura-2-loaded OC59 cells. A rapid and transient increase in [Ca(2+)](i) was observed in OC59 cells in response to the CPTH fragment hPTH-(53-84) (250 nM). No [Ca(2+)](i) signal was observed in COS-7 cells, in which CPTHR binding also cannot be detected. Neither hPTH-(1-34) nor a mutant CPTH analog, [Ala(55-57)]hPTH-(53-84), that does not to bind to CPTHRs, increased [Ca(2+)](i) in OC59 cells. The [Ca(2+)](i) response to hPTH-(53-84) required the presence of extracellular calcium and was blocked by inhibitors of voltage-dependent calcium channels (VDCCs), including nifedipine (100 nM), omega-agatoxin IVA (10 nM), and omega-conotoxin GVIA (100 nM). We conclude that activation of CPTHRs in OC59 osteocytic cells leads to a rapid increase in influx of extracellular calcium, most likely through the opening of VDCCs.

Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo.

We report for the first time that primary human neutrophils can undergo persistent, directionally biased movement away from a chemokine in vitro and in vivo, termed chemorepulsion or fugetaxis. Robust neutrophil chemorepulsion in microfluidic gradients of interleukin-8 (IL-8; CXC chemokine ligand 8) was dependent on the absolute concentration of chemokine, CXC chemokine receptor 2 (CXCR2), and was associated with polarization of cytoskeletal elements and signaling molecules involved in chemotaxis and leading edge formation. Like chemoattraction, chemorepulsion was pertussis toxin-sensitive and dependent on phosphoinositide-3 kinase, RhoGTPases, and associated proteins. Perturbation of neutrophil intracytoplasmic cyclic adenosine monophosphate concentrations and the activity of protein kinase C isoforms modulated directional bias and persistence of motility and could convert a chemorepellent to a chemoattractant response. Neutrophil chemorepulsion to an IL-8 ortholog was also demonstrated and quantified in a rat model of inflammation. The finding that neutrophils undergo chemorepulsion in response to continuous chemokine gradients expands the paradigm by which neutrophil migration is understood and may reveal a novel approach to our understanding of the homeostatic regulation of inflammation.

Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome.

The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance (MR) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group. Eligibility included Stage Ib-IIb previously untreated cervical tumours >10 cm(3). Neoadjuvant chemotherapy in 22 patients (methotrexate 300 mg x m(-2) (with folinic acid rescue), bleomycin 30 mg x m(-2), cisplatin 60 mg m(-2)) was repeated twice weekly for three courses and followed by radical hysterectomy. Post-operative radiotherapy was given in 14 cases. A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonrandomised control group. MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy. Changes were compared using a paired t-test. Survival was calculated using the Kaplan-Meier method. There were no significant differences between the neoadjuvant chemotherapy and control groups in age (mean, s.d. 43.3+/-10, 44.7+/-8.5 years, respectively, P=0.63) or tumour volume (medians, quartiles 35.8, 17.8, 57.7 cm(3) vs 23.0, 15.0, 37.0 cm(3), respectively, P=0.068). The reduction in tumour volume post-chemotherapy (median, quartiles 7.5, 3.0, 19.0 cm(3)) was significant (P=0.002). The reduction in -CH(2) triglyceride approached significance (P=0.05), but other metabolites were unchanged. The 3-year survival in the chemotherapy group (49.1%) was not significantly different from the control group (46%, P=0.94). There is a significant reduction in tumour volume and -CH(2) triglyceride levels after neoadjuvant chemotherapy, but there is no survival advantage.

Patterns of admissions for children with special needs to the paediatric assessment unit.

BACKGROUND: Children with special needs present a challenge to those involved in their care. AIMS: To determine the role of the acute assessment unit for these children. METHODS: Case notes and other records were reviewed for information on referrals, admissions, readmission within 7 and 28 days, length of stay, and management of 86 children registered for special needs. The study covered five years between January 1997 and December 2001. RESULTS: Of the 86 children, 48 (58%) were boys; 62 children had cerebral palsy and 52 learning disability. There were 914 episodes, with 44% of these being self referrals and 35% from general practitioners; 35.5% of the episodes were managed in the assessment unit. The average length of stay in hospital was 5 days, ranging from <24 hours to 63 days; 37.5% of those admitted to the ward stayed for less than 24 hours. Respiratory tract infections and seizures were the main reasons for referral and admission. CONCLUSION: Children with special needs tend to have a predictable pattern of conditions requiring inpatient care. One third of the inpatients episodes did not need a prolonged stay in hospital. This latter group of children could be managed at home with support of community nurses. Integrated care pathways need to be developed to minimise disruption to their lives. Appropriate resources should be made available to achieve these goals.

Variability in human quadriceps muscles: quantitative study and review of clinical literature.

Knowledge of variations in normal human thigh musculature is important for the interpretation of various clinical and biomedical investigations. In this study, cross-sections from whole thighs of 34 cadavers were analyzed qualitatively and morphometrically. Sections were cut from right and left limbs at three levels in the region often used for muscle biopsy. Measurements were made of limb circumferences and cross-sectional areas of the three vasti and of the femur, and of the extent of overlap and fusion between the vasti on the lateral aspect of the thigh. Limb circumference proved to be a good predictor of total cross-sectional area of the quadriceps muscle. Large individual variations were found for most measurements but especially for the amount of fusion between the muscle bellies of vastus lateralis and vastus intermedius. Significant differences were found for most variables between the three levels, but there were few differences between sides except for the cross-sectional area of vastus lateralis which was greater on the right at the most distal level. These variations in size and form of thigh musculature should be considered when interpreting data obtained from muscle biopsy, imaging, biomechanical, electromyographic, and functional studies of the human thigh. Review of the literature on variability of quadriceps muscle and its clinical relevance showed a diversity of approaches but insufficient definitive data suitable for interpreting functional outcomes in response to exercise or following surgery. Further work is suggested combining current anatomical datasets with advanced imaging techniques capable of determining muscle fiber orientation and fiber type composition, and including 3D reconstruction.