Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic.

BACKGROUND: Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease 2019 (COVID-19) pandemic. Progression of cancers during delay will impact on patients' long-term survival. PATIENTS AND METHODS: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of 3 and 6 months and periods of disruption of 1 and 2 years. Using health care resource costing, we contextualise attributable lives saved and life-years gained (LYGs) from cancer surgery to equivalent volumes of COVID-19 hospitalisations. RESULTS: Per year, 94 912 resections for major cancers result in 80 406 long-term survivors and 1 717 051 LYGs. Per-patient delay of 3/6 months would cause attributable death of 4755/10 760 of these individuals with loss of 92 214/208 275 life-years, respectively. For cancer surgery, average LYGs per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of 3/6 months (an average loss of 0.97/2.19 LYGs per patient), respectively. Taking into account health care resource units (HCRUs), surgery results on average per patient in 2.25 resource-adjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of 3/6 months. For 94 912 hospital COVID-19 admissions, there are 482 022 LYGs requiring 1 052 949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs. CONCLUSIONS: Modest delays in surgery for cancer incur significant impact on survival. Delay of 3/6 months in surgery for incident cancers would mitigate 19%/43% of LYGs, respectively, by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59%, respectively, when considering RALYGs. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.

Electron transport and room temperature single-electron charging in 10 nm scale PtC nanostructures formed by electron beam induced deposition.

Nanostructures of platinum-carbon nanocomposite material have been formed by electron-beam induced deposition. These consist of nanodots and nanowires with a minimum size ∼20 nm, integrated within ∼100 nm nanogap n-type silicon-on-insulator transistor structures. The nanodot transistors use ∼20 nm Pt/C nanodots, tunnel-coupled to Pt/C nanowire electrodes, bridging the Si nanogaps. Room-temperature single-electron transistor operation has been measured, and single-electron current oscillations and 'Coulomb diamonds' observed. In nanowire transistors, the temperature dependence from 290 to 8 K suggests that the current is a combination of thermally activated and tunnelling transport of carriers across potential barriers along the current path, and that the Pt/C is p-type at low temperature.

Pathologic characterization of genotypes XIV and XVII Newcastle disease viruses and efficacy of classical vaccination on specific pathogen-free birds.

To characterize the clinicopathologic features of recently described genotypes of Newcastle disease virus (NDV), 1 representative strain of genotype XIV and 2 of genotype XVII, all isolated from West Africa, were used to infect groups of ten 4-week-old specific pathogen-free chickens. The pathobiology of these 3 strains was compared to a South African NDV strain classified within genotype VII. All chickens infected with the 4 viruses died or were euthanized by day 4 postinfection due to the severity of clinical signs. Gross and histologic lesions in all infected chickens included extensive necrosis of lymphoid tissues (thymus, spleen, bursa of Fabricius, cecal tonsils, gut-associated lymphoid tissue), gastrointestinal necrosis and hemorrhages, and severe hemorrhagic conjunctivitis. Immunohistochemical staining revealed systemic viral distribution, and the most intense staining was in the lymphoid organs. Results demonstrate that the 3 West African strains from the previously uncharacterized genotypes XIV and XVII are typical velogenic viscerotropic NDV strains with lesions similar to the South African strain. Under experimental conditions, QV4 and LaSota NDV vaccine strains successfully protected chickens from morbidity and mortality against the genotype VII and one genotype XVII NDV strain, with no significant differences in the amount of virus shed when 2 vaccine schemes were compared.

Combined effects of endogenous sex hormone levels and mammographic density on postmenopausal breast cancer risk: results from the Breakthrough Generations Study.

BACKGROUND: Mammographic density and sex hormone levels are strong risk factors for breast cancer, but it is unclear whether they represent the same aetiological entity or are independent risk factors. METHODS: Within the Breakthrough Generations Study cohort, we conducted a case-control study of 265 postmenopausal breast cancer cases and 343 controls with prediagnostic mammograms and blood samples. Plasma was assayed for oestradiol, testosterone and sex hormone-binding globulin (SHBG) concentrations and mammographic density assessed by Cumulus. RESULTS: Oestradiol and testosterone were negatively and SHBG positively associated with percentage density and absolute dense area, but after adjusting for body mass index the associations remained significant only for SHBG. Breast cancer risk was independently and significantly positively associated with percentage density (P=0.002), oestradiol (P=0.002) and testosterone (P=0.007) levels. Women in the highest tertile of both density and sex hormone level were at greatest risk, with an odds ratio of 7.81 (95% confidence interval (CI): 2.89-21.1) for oestradiol and 4.57 (95% CI: 1.75-11.9) for testosterone and high density compared with those who were in the lowest tertiles. The cumulative risk of breast cancer in the highest oestradiol and density tertiles, representing 8% of controls, was estimated as 12.8% at ages 50-69 years and 19.4% at ages 20-79 years, and in the lowest tertiles was 1.7% and 4.3%, respectively. Associations of breast cancer risk with tertiles of mammographic dense area were less strong than for percentage density. CONCLUSIONS: Endogenous sex hormone levels and mammographic density are independent risk factors for postmenopausal breast cancer, which in combination can identify women who might benefit from increased frequency of screening and chemoprophylaxis.

Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive factors.

BACKGROUND: Women treated with supradiaphragmatic radiotherapy (sRT) for Hodgkin lymphoma (HL) at young ages have a substantially increased breast cancer risk. Little is known about how menarcheal and reproductive factors modify this risk. METHODS: We examined the effects of menarcheal age, pregnancy, and menopausal age on breast cancer risk following sRT in case-control data from questionnaires completed by 2497 women from a cohort of 5002 treated with sRT for HL at ages <36 during 1956-2003. RESULTS: Two-hundred and sixty women had been diagnosed with breast cancer. Breast cancer risk was significantly increased in patients treated within 6 months of menarche (odds ratio (OR) 5.52, 95% confidence interval (CI) (1.97-15.46)), and increased significantly with proximity of sRT to menarche (Ptrend<0.001). It was greatest when sRT was close to a late menarche, but based on small numbers and needing reexamination elsewhere. Risk was not significantly affected by full-term pregnancies before or after treatment. Risk was significantly reduced by early menopause (OR 0.55, 95% CI (0.35-0.85)), and increased with number of premenopausal years after treatment (Ptrend=0.003). CONCLUSION: In summary, this paper shows for the first time that sRT close to menarche substantially increases breast cancer risk. Careful consideration should be given to follow-up of these women, and to measures that might reduce their future breast cancer risk.

Tooth and cranial disparity in the fossil relatives of Sphenodon (Rhynchocephalia) dispute the persistent 'living fossil' label.

The tuatara (Sphenodon punctatus) is the only living representative of Rhynchocephalia, a group of small vertebrates that originated about 250 million years ago. The tuatara has been referred to as a living fossil; however, the group to which it belongs included a much greater diversity of forms in the Mesozoic. We explore the morphological diversity of Rhynchocephalia and stem lepidosaur relatives (Sphenodon plus 13 fossil relatives) by employing a combination of geometric morphometrics and comparative methods. Geometric morphometrics is used to explore cranium size and shape at interspecific scale, while comparative methods are employed to test association between skull shape and size and tooth number after taking phylogeny into account. Two phylogenetic topologies have been considered to generate a phylomorphospace and quantify the phylogenetic signal in skull shape data, the ancestral state reconstruction as well as morphological disparity using disparity through time plots (DTT). Rhynchocephalia exhibit a significant phylogenetic signal in skull shape that compares well with that computed for other extinct vertebrate groups. A consistent form of allometry has little impact on skull shape evolution while the number of teeth significantly correlates with skull shape also after taking phylogeny into account. The ancestral state reconstruction demonstrates a dramatic shape difference between the skull of Sphenodon and its much larger Cretaceous relative Priosphenodon. Additionally, DTT demonstrates that skull shape disparity is higher between rather than within clades while the opposite applies to skull size and number of teeth. These results were not altered by the use of competing phylogenic hypotheses. Rhynchocephalia evolved as a morphologically diverse group with a dramatic radiation in the Late Triassic and Early Jurassic about 200 million years ago. Differences in size are not marked between species whereas changes in number of teeth are associated with co-ordinated shape changes in the skull to accommodate larger masticatory muscles. These results show that the tuatara is not the product of evolutionary stasis but that it represents the only survivor of a diverse Mesozoic radiation whose subsequent decline remains to be explained.

The Breakthrough Generations Study: design of a long-term UK cohort study to investigate breast cancer aetiology.

BACKGROUND: The rationale, design, recruitment and follow-up methods are described for the Breakthrough Generations Study, a UK cohort study started in 2003, targeted at investigation of breast cancer aetiology. METHODS: Cohort members have been recruited by a participant referral method intended to assemble economically a large general population cohort from whom detailed questionnaire information and blood samples can be obtained repeatedly over decades, with high completeness of follow-up and inclusion of large numbers of related individuals. 'First-generation' recruits were women contacted directly, or who volunteered directly, to join the study. They nominated female friends and family, whom we contacted, and those who joined ('second generation') nominated others, reiterated for up to 28 generations. RESULTS: The method has successfully been used during 2003-2011 to recruit 112,049 motivated participants with a broad geographic and socioeconomic distribution, aged 16-102 years, who have completed detailed questionnaires; 92% of the participants gave blood samples at recruitment. When eligible, 2½ years after recruitment, >98% completed the first follow-up questionnaire. Thirty percent are first-degree relatives of other study members. CONCLUSION: The 'generational' recruitment method has enabled recruitment of a large cohort who appear to have the commitment to enable long-term continuing data and sample collection, to investigate the effects of changing endogenous and exogenous factors on cancer risk.

Evidence that disease-induced population decline changes genetic structure and alters dispersal patterns in the Tasmanian devil.

Infectious disease has been shown to be a major cause of population declines in wild animals. However, there remains little empirical evidence on the genetic consequences of disease-mediated population declines, or how such perturbations might affect demographic processes such as dispersal. Devil facial tumour disease (DFTD) has resulted in the rapid decline of the Tasmanian devil, Sarcophilus harrisii, and threatens to cause extinction. Using 10 microsatellite DNA markers, we compared genetic diversity and structure before and after DFTD outbreaks in three Tasmanian devil populations to assess the genetic consequences of disease-induced population decline. We also used both genetic and demographic data to investigate dispersal patterns in Tasmanian devils along the east coast of Tasmania. We observed a significant increase in inbreeding (F(IS) pre/post-disease -0.030/0.012, P<0.05; relatedness pre/post-disease 0.011/0.038, P=0.06) in devil populations after just 2-3 generations of disease arrival, but no detectable change in genetic diversity. Furthermore, although there was no subdivision apparent among pre-disease populations (θ=0.005, 95% confidence interval (CI) -0.003 to 0.017), we found significant genetic differentiation among populations post-disease (θ=0.020, 0.010-0.027), apparently driven by a combination of selection and altered dispersal patterns of females in disease-affected populations. We also show that dispersal is male-biased in devils and that dispersal distances follow a typical leptokurtic distribution. Our results show that disease can result in genetic and demographic changes in host populations over few generations and short time scales. Ongoing management of Tasmanian devils must now attempt to maintain genetic variability in this species through actions designed to reverse the detrimental effects of inbreeding and subdivision in disease-affected populations.

Structure and compositional characteristics of caniniform dental enamel in the tuatara Sphenodon punctatus (Lepidosauria: Rhynchocephalia).

OBJECTIVE: The evolution of dental tissues in relation to tooth function is poorly understood in non-mammalian vertebrates. We studied the dentition of Sphenodon punctatus, the sole remaining member of the order Rhynchocephalia in this light. METHODS: We examined 6 anterior maxillary caniniform teeth from adult Sphenodon by scanning electron microscopy, nano-indentation and Raman spectroscopy. RESULTS: The elastic modulus (E) for tuatara enamel was 73.17 (sd, 3.25) GPa and 19.52 +/- 0.76 Gpa for dentine. Hardness (H) values for enamel and dentine were 4.00 (sd, 0.22) and 0.63 +/- 0.02 Gpa respectively. The enamel was thin (100 gm or less), prismless and consisted of grouped parallel crystallites. Incremental lines occurred at intervals of about 0.5 to 1 rm. There were tubular structures along the enamel dentine junction running from the dentine into the inner enamel, at different angles. These were widened at their base with a smooth, possibly inorganic lining. Enamel elastic modulus and hardness were lower than those for mammals. CONCLUSIONS: The presence of enamel tubules in the basal part of the enamel along the EDJ remains speculative, with possible functions being added enamel/dentinal adhesion or a role in mechanosensation.

Determinants of age at menarche in the UK: analyses from the Breakthrough Generations Study.

BACKGROUND: Early menarche increases breast cancer risk but, aside from weight, information on its determinants is limited. METHODS: Age at menarche data were collected retrospectively by questionnaire from 81,606 women aged 16-98, resident in the UK and participating in the Breakthrough Generations Study. RESULTS: Menarche occurred earlier in women who had a low birthweight (P(trend)<0.001), were singletons (P<0.001), had prenatal exposure to pre-eclampsia (P<0.001) or maternal smoking (P=0.01), were not breastfed (P(trend)=0.03), were non-white (P<0.001), were heavy (P(trend)<0.001) or tall (P(trend)<0.001) compared with their peers at age 7 and exercised little as a child (P(trend)<0.001). Menarcheal age increased with number of siblings (P<0.001) independently of birth order, and had an inverse association with birth order after adjustment for sibship size (P<0.001). In a multivariate model, birthweight, ethnicity, weight, height, exercise, sibship size and birth order remained significant, and maternal age at birth became significant (positive association, P<0.001). CONCLUSION: Age at menarche was influenced by both pre- and post-natal factors, and these factors may affect breast cancer risk through this route.

A clinical trial assessing the safety and efficacy of the CB1R inverse agonist taranabant in obese and overweight patients: low-dose study.

OBJECTIVE: To evaluate the weight loss efficacy, safety and tolerability of taranabant, a CB1R inverse agonist, in obese and overweight patients. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SUBJECTS: Patients >or=18 years old, BMI 27-43 kg m(-2), were randomized to placebo (n=209) or taranabant 0.5 mg (n=207), 1 mg (n=208) or 2 mg given orally once daily (n=417) for 52 weeks. MEASUREMENTS: Key efficacy measurements included body weight (BW), waist circumference (WC), lipid endpoints and glycemic endpoints. RESULTS: Based on a last observation carried forward analysis of the all-patients-treated population, mean change in BW for taranabant 0.5, 1, and 2 mg and placebo was -5.4, -5.3, -6.7 and -1.7 kg, respectively (P<0.001 for all doses vs placebo). The proportions of patients who lost at least 5 and 10% of their baseline BW at week 52 were significantly higher for all taranabant doses vs placebo (P<0.001 for all doses). Reductions in WC, percentage of body fat, and triglycerides were significant for taranabant 2 mg and in triglycerides for taranabant 1 mg vs placebo. There was no effect of taranabant vs placebo on other lipid or glucose-related endpoints. Incidences of adverse experiences classified in the gastrointestinal (diarrhea and nausea), nervous system (dizziness/dizziness postural), psychiatric-related (irritability and anger/aggression) and vascular (flushing/hot flush) organ systems were higher and statistically significant in the taranabant 2-mg group compared with the placebo group. Irritability was higher and statistically significant in all taranabant groups compared with the placebo group. CONCLUSION: All three doses of taranabant-induced clinically meaningful and statistically significant weight loss. Incidences of adverse experiences in organ systems known to express CB1R were higher in taranabant groups.

Trends in weights, heights, BMI and comparison of their differences in urban and rural areas for Iranian children and adolescents 2-18-year-old between 1990-1991 and 1999.

BACKGROUND: Secular trends in height and weight are interesting because in middle- and low-income countries they are a marker for changes in population health. The present study aims to evaluate the secular trend in height and weight and body mass index (BMI) of Iranian children and adolescents aged 2-18 years old between 1990-1991 and 1999 and compare the magnitude of urban-rural differences during this period for the first time in an Asian country. METHODS: Data from two national health surveys in 1990-1991 and 1999, of 22,349 and 25,196 weight and height measures of Iranian children and adolescents were used to study the trend and compare its difference in urban and rural children. Logarithmic transformation of weight, height and BMI was modelled as a polynomial in age for urban and rural boys and girls in each survey separately. The trend in urban and rural growth indexes (weight, height and BMI) and also the comparisons of urban-rural differences between two national surveys were tested in logarithmic scale using a weighted form of Z statistic for comparison of two means adjusted for age groups. RESULTS: Urban and rural boys and girls became taller and heavier (P≤ 0.02) with no change of BMI (P > 0.05) during the period. There was not any significant difference between the magnitudes of urban-rural difference between two surveys (P≥ 0.61). CONCLUSION: Although generally positive weight and height trend was observed among urban and rural residents, the magnitude of their differences was not changed.

Cutaneous overexpression of NT-3 increases sensory and sympathetic neuron number and enhances touch dome and hair follicle innervation.

Target-derived influences of nerve growth factor on neuronal survival and differentiation are well documented, though effects of other neurotrophins are less clear. To examine the influence of NT-3 neurotrophin overexpression in a target tissue of sensory and sympathetic neurons, transgenic mice were isolated that overexpress NT-3 in the epidermis. Overexpression of NT-3 led to a 42% increase in the number of dorsal root ganglia sensory neurons, a 70% increase in the number of trigeminal sensory neurons, and a 32% increase in sympathetic neurons. Elevated NT-3 also caused enlargement of touch dome mechanoreceptor units, sensory end organs innervated by slowly adapting type 1 (SA1) neurons. The enlarged touch dome units of the transgenics had an increased number of associated Merkel cells, cells at which SA1s terminate. An additional alteration of skin innervation in NT-3 transgenics was an increased density of myelinated circular endings associated with the piloneural complex. The enhancement of innervation to the skin was accompanied by a doubling in the number of sensory neurons expressing trkC. In addition, measures of nerve fibers in cross-sectional profiles of cutaneous saphenous nerves of transgenics showed a 60% increase in myelinated fibers. These results indicate that in vivo overexpression of NT-3 by the epidermis enhances the number of sensory and sympathetic neurons and the development of selected sensory endings of the skin.

Estrogen and spermatogenesis.

Although it has been known for many years that estrogen administration has deleterious effects on male fertility, data from transgenic mice deficient in estrogen receptors or aromatase point to an essential physiological role for estrogen in male fertility. This review summarizes the current knowledge on the localization of estrogen receptors and aromatase in the testis in an effort to understand the likely sites of estrogen action. The review also discusses the many studies that have used models employing the administration of estrogenic substances to show that male fertility is responsive to estrogen, thus providing a mechanism by which inappropriate exposure to estrogenic substances may cause adverse effects on spermatogenesis and male fertility. The reproductive phenotypes of mice deficient in estrogen receptors alpha and/or beta and aromatase are also compared to evaluate the physiological role of estrogen in male fertility. The review focuses on the effects of estrogen administration or deprivation, primarily in rodents, on the hypothalamo-pituitary-testis axis, testicular function (including Leydig cell, Sertoli cell, and germ cell development and function), and in the development and function of the efferent ductules and epididymis. The requirement for estrogen in normal male sexual behavior is also reviewed, along with the somewhat limited data on the fertility of men who lack either the capacity to produce or respond to estrogen. This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered "male hormones."

Challenges in the diagnosis of leptospirosis outwith endemic settings: a Scottish single centre experience.

Background Leptospirosis is a zoonotic infection occurring worldwide but endemic in tropical countries. This study describes diagnostic testing for leptospirosis at our institution in Scotland over a 10-year period. Method We identified patients with blood samples referred to the Public Health England reference laboratory for leptospirosis testing between 2006 and 2016. Results A total of 480 samples were sent for IgM ELISA testing with 26 positive results from 14 patients. Two patients met criteria for 'confirmed' leptospirosis (microscopic agglutination test > 1:320 in one case and a positive PCR in the other) and the remaining 12 were 'probable' on the basis of IgM ELISA positivity, though 9 did not have microscopic agglutination testing performed. Nine infections were imported, mostly from Asia and with a history of fresh water exposure. Three co-infections (respiratory syncytial virus, influenza B and Campylobacter sp.) were identified. Conclusions Practical issues with microscopic agglutination testing (insufficient blood sent to reference laboratory) and PCR (travellers returning > 7 days after illness onset) represent challenges to the laboratory confirmation of a clinical diagnosis of leptospirosis. Co-infection and infectious/auto-immune causes of false positive serology should be evaluated.

Estrogen and adiposity--utilizing models of aromatase deficiency to explore the relationship.

Estrogen has an important role to play in energy homeostasis in both men and mice. Lack of estrogen results in the development of a metabolic syndrome in humans and rodents, including excess adiposity, hepatic steatosis (in male but not female aromatase knockout (ArKO) mice) and insulin resistance. Estrogen replacement results in a prompt reversal of the energy imbalance symptoms associated with estrogen deficiency. A corollary to the perturbed energy balance observed in the ArKO mouse is the death by apoptosis of dopaminergic neurons in the hypothalamic arcuate nucleus of male ArKO mice, an area of the brain pivotal to the regulation of energy uptake, storage, and mobilisation. An extension of our work exploring the relationship between estrogen and adiposity has been to examine the role played by androgens in energy balance. We have demonstrated that an increased androgen to estrogen ratio can promote visceral fat accumulation in the rodent by inhibiting AMPK activation and stimulating lipogenesis. Therefore, understanding the regulation of energy homeostasis is becoming an increasingly fascinating challenge, as the number of contributors, their communications, and the complexity of their interactions, involved in the preservation of this equilibrium continues to increase. Models of aromatase deficiency, both naturally occurring and engineered, will continue to provide valuable insights into energy homeostasis.

In-vitro profile of a new beta-lactam, ceftobiprole, with activity against methicillin-resistant Staphylococcus aureus.

Ceftobiprole is a novel, broad-spectrum cephalosporin with in-vitro activity against common Gram-positive and Gram-negative organisms. It forms a stable inhibitory complex with Staphylococcus aureus penicillin-binding protein (PBP) 2' (2a), resulting in enhanced activity against methicillin-resistant S. aureus (MRSA). In recent studies of methicillin-susceptible S. aureus, the ceftobiprole MIC(90) value was most frequently < or =1.0 mg/L (MIC range < or =0.25-1.0 mg/L). For MRSA, MIC(90) values were generally 2.0 mg/L (MIC range < or =0.06-4.0 mg/L). MICs for all streptococcal species, except penicillin-resistant Streptococcus viridans but including penicillin-resistant Streptococcus pneumoniae, ranged from < or =0.008 to 2.0 mg/L. Ceftobiprole is active against Enterococcus faecalis (MIC(90) = 4 mg/L), but not generally active against Enterococcus faecium (MIC(90) > 16 mg/L). Ceftobiprole displayed bactericidal activity against Gram-negative pathogens comparable to that of cefepime, ceftazidime or piperacillin-tazobactam in early studies. However, recent data show activity against Pseudomonas aeruginosa similar to that of cefepime but less than that of ceftazidime. Ceftobiprole, like cefepime, is stable in the presence of most class A non-extended spectrum beta-lactamases and inducible class C beta-lactamases. Ceftobiprole is a poor inducer of AmpC beta-lactamase and a poor substrate for hydrolysis by AmpC beta-lactamase. Studies of ceftobiprole in several animal models have demonstrated potent in-vivo efficacy against infections caused by MRSA, including strains intermediately resistant to vancomycin. It was also efficacious in murine infections caused by Gram-negative bacteria with MIC values < or =2 mg/L. The broad spectrum of activity demonstrated by ceftobiprole in vitro and in vivo suggests that it may have potential for empirical treatment of suspected Gram-negative and Gram-positive infections, including those caused by MRSA.

Plexiform neurofibroma with dual nerve origin within the palm: a case report.

We describe a unique case of a 44-year-old gentleman who presented to our hand department with a history of a lump within his right palm that spanned several decades. Its gradual increase in size together with pain on palpation merited further investigation and subsequent surgical excision. Extensive tumour emanating from both ulnar and median nerves was resected, the histopathological diagnosis of which was plexiform neurofibroma. We believe this is the first description of an isolated plexiform neurofibroma of the hand with dual nerve origin.

Sleep and rest regulation in young and old oestrogen-deficient female mice.

The effect of circulating oestrogen deficiency on sleep regulation and locomotor activity was investigated in aromatase cytochrome P450 deficient mice (ArKO) and wild-type (WT) controls. Sleep was recorded in 3-month old mice during a 24-h baseline day, 6-h sleep deprivation (SD) and 18-h recovery, and activity was recorded at the age of 3, 9 and 12 months. In mice deficient of oestrogen, the total amount of sleep per 24 h was the same as in WT controls. However, in ArKO mice, sleep was enhanced in the dark period at the expense of sleep in the light phase, and was more fragmented than sleep in WT mice. This redistribution of sleep resulted in a damped amplitude of slow-wave activity (SWA; power between 0.75-4.0 Hz) in non-rapid eye movement sleep across 24 h. After SD, the rebound of sleep and SWA was similar between the genotypes, suggesting that oestrogen deficiency does not affect the mechanisms maintaining the homeostatic balance between the amount of sleep and its intensity. Motor activity decreased with age in both genotypes and was lower in ArKO mice compared to WT at all three ages. After SD, the amount of rest in 3-month old WT mice increased above baseline and was more consolidated. Both effects were less pronounced in ArKO mice, reflecting the baseline differences between the genotypes. The results indicate that despite the pronounced redistribution of sleep and motor activity in oestrogen deficient mice, the basic homeostatic mechanisms of sleep regulation in ArKO mice remain intact.

Geographically-based evaluation of multidrug resistance trends among Streptococcus pneumoniae in the USA: findings of the FAST surveillance initiative (2003-2004).

Surveillance initiatives to track Streptococcus pneumoniae resistance trends are important for understanding the current in vitro effectiveness of available antimicrobial agents. The antimicrobial susceptibility profiles of S. pneumoniae (n=1479 isolates) collected from 17 geographical areas across the USA (2003-2004) were analysed; 36.8% of isolates were resistant to one or more agents (24.4% were multidrug-resistant, i.e. resistant to two or more antimicrobial classes). Multidrug resistance involved resistance to beta-lactams, macrolides, tetracycline and trimethoprim/sulphamethoxazole, but rarely fluoroquinolones (>96% of multidrug-resistant isolates were fluoroquinolone-susceptible). Multidrug resistance rates were prominent regardless of the geographical region surveyed. As this trend continues, the empirical therapeutic options for S. pneumoniae infections will diminish and there will be an ongoing need to evaluate the effectiveness of potent fluoroquinolones such as gemifloxacin.