Was "variations of reproductive development" considered?
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Disorders of Sex Development↗
Biomedical subjects
M Simmonds
Publications and source records attributed to M Simmonds.
Interventions for the prevention and management of neck/upper extremity musculoskeletal conditions: a systematic review.
Considered from medical, social or economic perspectives, the cost of musculoskeletal injuries experienced in the workplace is substantial, and there is a need to identify the most efficacious interventions for their effective prevention, management and rehabilitation. Previous reviews have highlighted the limited number of studies that focus on upper extremity intervention programmes. The aim of this study was to evaluate the findings of primary, secondary and/or tertiary intervention studies for neck/upper extremity conditions undertaken between 1999 and 2004 and to compare these results with those of previous reviews. Relevant studies were retrieved through the use of a systematic approach to literature searching and evaluated using a standardised tool. Evidence was then classified according to a "pattern of evidence" approach. Studies were categorised into subgroups depending on the type of intervention: mechanical exposure interventions; production systems/organisational culture interventions and modifier interventions. 31 intervention studies met the inclusion criteria. The findings provided evidence to support the use of some mechanical and modifier interventions as approaches for preventing and managing neck/upper extremity musculoskeletal conditions and fibromyalgia. Evidence to support the benefits of production systems/organisational culture interventions was found to be lacking. This review identified no single-dimensional or multi-dimensional strategy for intervention that was considered effective across occupational settings. There is limited information to support the establishment of evidence-based guidelines applicable to a number of industrial sectors.
Cost-Benefit Analysis↗
The genome of the social amoeba Dictyostelium discoideum.
The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
ATP-Binding Cassette Transporters↗
Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.
We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.
Acute Disease↗
Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.
Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.
Animals↗
The genome sequence of Schizosaccharomyces pombe.
We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.
Base Sequence↗
Predictors of outcome of mammography in the National Health Service Breast Screening Programme.
BACKGROUND: Little is known about the factors influencing the risk of recall for assessment, invasive diagnostic procedures, and early rescreening after screening mammography. METHODS: From June 1996 to March 1998 women attending screening at 10 National Health Service Breast Screening Programme (NHSBSP) centres completed a self administered questionnaire and were followed up for their screening outcome. RESULTS: 1969 (3.3%) out of 60 443 women aged 50-64 who had never used hormone replacement therapy (HRT) were recalled for assessment but were not diagnosed with breast cancer (defined here as false positive recall). After adjustment for the variation between centres, false positive recall was decreased significantly among women who were likely to have had a previous NHSBSP mammogram (odds ratio (OR) 0.49, 95% confidence interval (95% CI) 0.38 to 0.63 for likely versus unlikely), who were postmenopausal (OR 0.65, 95% CI 0.56 to 0.76 for postmenopausal v premenopausal) and increased significantly for women reporting previous breast surgery (OR 1.64, 95% CI 1.42 to 1.89). Although false positive recall decreased significantly with parity and increasing body mass index, these effects were not large and no significant variation was found with age, education, family history of breast cancer, oral contraceptive use, sterilisation, exercise, smoking, or alcohol consumption. Altogether 655 (1.1%) women had an invasive diagnostic procedure; no personal characteristics were predictive of this outcome, 286(0.5%) were referred for early rescreening, and this was increased significantly by nulliparity and a family history of breast cancer. INTERPRETATION: Premenopausal women, those without a previous NHSBSP mammogram, and women with previous breast surgery have an increased risk of false positive recall by the NHSBSP.
Age Factors↗
Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.
Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.
Chromosome Mapping↗
Genome sequence of Yersinia pestis, the causative agent of plague.
The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.
Animals↗
VN training scheme.
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Animal Technicians↗
Massive gene decay in the leprosy bacillus.
Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.
Animals↗
Visual loss due to progressive multifocal leukoencephalopathy in a congenital immunodeficiency disorder.
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Adult↗
Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer pain.
This open-label study evaluated the long-term safety and tolerability of oral transmucosal fentanyl citrate (OTFC) in ambulatory cancer patients with breakthrough pain undergoing cancer care at 32 university- or community-based practices. Patients had participated in a previous short-term titration trial of OTFC, were experiencing at least one episode per day of breakthrough pain, and had achieved relief of their breakthrough pain with an opioid. Patients received OTFC units at a starting dosage strength determined in the short-term trial (200-1600 microg). Outcome measures included number of successfully treated breakthrough pains, global satisfaction rating (0 = poor through 4 = excellent), and side effects. In total, 41,766 units of OTFC were used to treat 38,595 episodes of breakthrough pain in 155 patients. Number of treatment days ranged from 1 to 423 (mean, 91 days). Patients averaged 2.9 breakthrough pain episodes per day. About 92% of episodes were successfully treated with OTFC and there was no trend toward decreased effectiveness over time. Most patients (61%) did not require dose escalation during treatment. Global satisfaction ratings were consistently above 3, indicating very good to excellent relief. Common adverse events associated with OTFC were somnolence (9%), constipation (8%), nausea (8%), dizziness (8%), and vomiting (5%). Six patients (4%) discontinued therapy due to an OTFC-related adverse event. There were no reports of abuse and no concerns about the safety of the drug raised by patients or families. OTFC was used safely and effectively during long-term treatment of breakthrough pain in cancer patients at home.
Administration, Oral↗
EGF-responsive neural stem cells are a transient population in the developing mouse spinal cord.
The adult mouse forebrain, which exhibits substantial ongoing cell genesis, contains self-renewing multipotent neural stem cells that respond to epidermal growth factor (EGF), but the adult spinal cord, which exhibits limited cell genesis, does not. Spinal cord development is a process characterized by defined periods of cell histogenesis. Thus, in the present study we asked whether EGF-responsive neural stem cells are present within the spinal cord during development. At embryonic day (E) 11, subsequent to the onset of neurogenesis, only fibroblast growth factor (FGF) receptors and FGF-2 (requiring heparan sulphate)-responsive stem cells are present in the spinal cord. Between E12 and 14, at the peak of spinal cord neurogenesis and the onset of gliogenesis, EGF receptors appear along with clonally derived highly expandable EGF-responsive neural stem cells. Following the cessation of cell histogenesis, the adult spinal cord is largely devoid of both EGF receptors and EGF-responsive stem cells. On the other hand, the FGF receptor1c subtype and multipotent FGF-2-responsive neural stem cells are present in early development and in the adult. The order of appearance of spinal cord neural stem cells and in vitro lineage analysis suggests that a more primitive FGF-2-responsive stem cell produces the EGF-responsive stem cell. These findings suggest that EGF-responsive neural stem cells appear transiently in the spinal cord, during the peak period of cell histogenesis, but are no longer present in the relatively quiescent adult structure.
Animals↗
Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene sequences.
Salmonella enterica serotype Typhi differs from nontyphoidal Salmonella serotypes by its strict host adaptation to humans and higher primates. Since fimbriae have been implicated in host adaptation, we investigated whether the serotype Typhi genome contains fimbrial operons which are unique to this pathogen or restricted to typhoidal Salmonella serotypes. This study established for the first time the total number of fimbrial operons present in an individual Salmonella serotype. The serotype Typhi CT18 genome, which has been sequenced by the Typhi Sequencing Group at the Sanger Centre, contained a type IV fimbrial operon, an orthologue of the agf operon, and 12 putative fimbrial operons of the chaperone-usher assembly class. In addition to sef, fim, saf, and tcf, which had been described previously in serotype Typhi, we identified eight new putative chaperone-usher-dependent fimbrial operons, which were termed bcf, sta, stb, ste, std, stc, stg, and sth. Hybridization analysis performed with 16 strains of Salmonella reference collection C and 22 strains of Salmonella reference collection B showed that all eight putative fimbrial operons of serotype Typhi were also present in a number of nontyphoidal Salmonella serotypes. Thus, a simple correlation between host range and the presence of a single fimbrial operon seems at present unlikely. However, the serotype Typhi genome differed from that of all other Salmonella serotypes investigated in that it contained a unique combination of putative fimbrial operons.
Base Sequence↗
Effective selective head cooling during posthypoxic hypothermia in newborn piglets.
Selective head cooling has been proposed as a neuroprotective intervention after hypoxia-ischemia in which the brain is cooled without subjecting the rest of the body to significant hypothermia, thus minimizing adverse systemic effects. There are little data showing it is possible to cool the brain more than the body. We have therefore applied selective head cooling to our hypoxia-ischemia piglet model to establish whether it is possible. Nine piglets were anesthetized, and brain temperature was measured at the surface and in the superficial (0.2 cm) and deep (1.7-2.0 cm) gray matter. Rectal (6-cm depth), skin, and scalp temperatures (T) were recorded continuously. Lowering T-rectal from normothermia (39 degrees C) to hypothermia (33.5-33.8 degrees C) using a head cap perfused with cold (6-24 degrees C) water was undertaken for up to 6 h. To assess the impact of the 45-min hypoxia-ischemia insult on the effectiveness of selective head cooling, four piglets were cooled both before and after the insult, and four, only afterward. During selective head cooling, it was possible to achieve a lower T-deep brain than T-rectal in all animals both before and after hypoxia. However, this was only possible when overhead body heating was used. The T-rectal to T-deep brain gradient was significantly smaller after the insult (median, 5.3 degrees C; range, 4.2-8.5 degrees C versus 3.0 degrees C; 1.7-7.4 degrees C; p = 0.008). During rewarming to normothermia, the gradient was maintained at 4.5 degrees C. We report for the first time a study, which by direct measurement of deep intracerebral temperatures, validates the cooling cap as an effective method of selective brain cooling in a newborn animal hypoxia-ischemia model.
Animals↗
Assessment of stranded cetaceans.
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Animals↗
Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491.
Neisseria meningitidis causes bacterial meningitis and is therefore responsible for considerable morbidity and mortality in both the developed and the developing world. Meningococci are opportunistic pathogens that colonize the nasopharynges and oropharynges of asymptomatic carriers. For reasons that are still mostly unknown, they occasionally gain access to the blood, and subsequently to the cerebrospinal fluid, to cause septicaemia and meningitis. N. meningitidis strains are divided into a number of serogroups on the basis of the immunochemistry of their capsular polysaccharides; serogroup A strains are responsible for major epidemics and pandemics of meningococcal disease, and therefore most of the morbidity and mortality associated with this disease. Here we have determined the complete genome sequence of a serogroup A strain of Neisseria meningitidis, Z2491. The sequence is 2,184,406 base pairs in length, with an overall G+C content of 51.8%, and contains 2,121 predicted coding sequences. The most notable feature of the genome is the presence of many hundreds of repetitive elements, ranging from short repeats, positioned either singly or in large multiple arrays, to insertion sequences and gene duplications of one kilobase or more. Many of these repeats appear to be involved in genome fluidity and antigenic variation in this important human pathogen.
Antigenic Variation↗