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A Smith

Publications and source records attributed to A Smith.

At least 19 recordsLinked to original sources
PubMed2023

Exploiting Real-Time Genomic Surveillance Data To Assess 4CMenB Meningococcal Vaccine Performance in Scotland, 2015 to 2022.

The United Kingdom implemented the first national infant immunization schedule for the meningococcal vaccine 4CMenB (Bexsero) in September 2015, targeting serogroup B invasive meningococcal disease (IMD). Bexsero contains four variable subcapsular proteins, and postimplementation IMD surveillance was necessary, as nonhomologous protein variants can evade Bexsero-elicited protection. We investigated postimplementation IMD cases reported in Scotland from 1 September 2015 to 30 June 2022. Patient demographics and vaccination status were combined with genotypic data from the causative meningococci, which were used to assess vaccine coverage with the meningococcal deduced vaccine antigen reactivity (MenDeVAR) index. Eighty-two serogroup B IMD cases occurred in children >5 years of age, 48 (58.5%) of which were in unvaccinated children and 34 (41%) of which were in children who had received ≥1 Bexsero dose. Fifteen of the 34 vaccinated children had received one dose, 17 had received two doses, and two had received three doses. For 39 cases, meningococcal sequence data were available, enabling MenDeVAR index deductions of vaccine-preventable (M-VP) and non-vaccine-preventable (M-NVP) meningococci. Notably, none of the 19 of the children immunized ≥2 times had IMD caused by M-VP meningococci, with 2 cases of NVP meningococci, and no deduction possible for 17. Among the 15 children partially vaccinated according to schedule (1 dose), 7 were infected by M-VP meningococci and 2 with M-NVP meningococci, with 6 for which deductions were not possible. Of the unvaccinated children with IMD, 40/48 were ineligible for vaccination and 20/48 had IMD caused by M-VP meningococci, with deductions not being possible for 14 meningococci. IMPORTANCE This study demonstrates the value of postimplementation genomic surveillance of vaccine-preventable pathogens in providing information on real-world vaccine performance. The data are consistent with 2 and 3 doses of Bexsero, delivered according to schedule, providing good protection against invasive disease caused by meningococci deduced from genomic data to be vaccine preventable. Single doses provide poorer protection to infants. In practical terms, these data can provide public health reassurance when vaccinated individuals develop IMD with non-vaccine-preventable variants. They further indicate that additional testing is needed on variants for which no immunological data exist to improve estimates of protection, although these data suggest that the uncharacterized variants are unlikely to be covered by Bexsero. Finally, the confirmation that incomplete or absent doses in infancy lead to reduced protection supports public health and general practitioners in promoting vaccination according to schedule.

Infant↗
PubMed2007

CT assessment of anastomotic bowel leak.

AIM: To evaluate the predictors of clinically important gastrointestinal anastomotic leaks using multidetector computed tomography (CT). SUBJECTS AND METHODS: Ninety-nine patients, 73 with clinical suspicion of anastomotic bowel leak and 26 non-bowel surgery controls underwent CT to investigate postoperative sepsis. Fifty patients had undergone large bowel and 23 small bowel anastomoses. The time interval from surgery was 3-30 days (mean 10+/-5.9 SD) for the anastomotic group and 3-40 days (mean 14+/-11 SD) for the control group (p=0.3). Two radiologists blinded to the final results reviewed the CT examinations in consensus and recorded the presence of peri-anastomotic air, fluid or combination of the two; distant loculated fluid or combination of fluid and air; free air or fluid; and intestinal contrast leak. Final diagnosis of clinically important anastomotic leak (CIAL) was confirmed at surgery or by chart review of predetermined clinical and laboratory criteria. RESULTS: The prevalence of CIAL in the group undergoing CT was 31.5% (23/73). The CT examinations with documented leak were performed 5-28 (mean; 11.4+/-6 SD) days after surgery. Nine patients required repeat operation, 10 percutaneous abscess drainage, two percutaneous drainage followed by surgery, and two prolonged antibiotic treatment and total parenteral nutrition (TPN). Of the CT features examined, only peri-anastomotic loculated fluid containing air was more frequently seen in the CIAL group as opposed to the no leak group (p=0.04). There was no intestinal contrast leakage in this cohort. Free air was present up to 9 days and loculated air up to 26 days without CIAL. CONCLUSION: Most postoperative CT features overlap between patients with and without CIAL. The only feature seen statistically more frequently with CIAL is peri-anastomotic loculated fluid containing air.

Abscess↗
PubMed2006

A painless method of ultrasonically assisted debridement of chronic leg ulcers: a pilot study.

OBJECTIVES: Devitalized tissue in a recalcitrant leg ulcer is common and may impede healing. The aim of this study was to evaluate the use of a non-invasive low frequency ultrasound device to debride chronic leg ulcers as an adjunct to compression bandages therapy. METHODS: 19 patients with leg ulceration of at least 6 months were recruited. Low frequency ultrasound at 25kHz was delivered by a portable Sonaca--180 via a handheld probe, using normal saline as the irrigation/coupling medium. The ultrasound was applied for 10-20 seconds per probe head area onto the ulcer. Each leg underwent treatment at an interval of 2-3 weeks with compression bandages reapplied at the end of the treatment. Serial colour photographs were taken to evaluate the response at each visit. RESULTS: Each patient received on average 5.7 treatments each ranged from 5-20 minutes depending on the ulcer size. Symptomatic relief (pain and odour reduction) was achieved in 6 patients. 7 patients achieved complete ulcer healing (mean ulcer size=4.72+/-SD 1.872cm(2)) but no response was observed in 8 patients. There were no major complications of the treatment which was relatively painless. CONCLUSIONS: The application of low frequency ultrasound debridement may heal some recalcitrant ulcers when standard compression regimens have failed. It is cheap and does not require admission. The role of simple wound cleansing requires further investigation.

Adolescent↗
PubMed2006

Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening.

BACKGROUND: The identification of BRCA1 and BRCA2 mutations in familial breast cancer kindreds allows genetic testing of at-risk relatives. Those who test negative are usually reassured and additional breast cancer surveillance is discontinued. However, we postulated that in high-risk families, such as those seen in clinical genetics centres, the risk of breast cancer might be influenced not only by the BRCA1/BRCA2 mutation but also by modifier genes. One manifestation of this would be the presence of phenocopies in BRCA1/BRCA2 kindreds. METHODS: 277 families with pathogenic BRCA1/BRCA2 mutations were reviewed and 28 breast cancer phenocopies identified. The relative risk of breast cancer in those testing negative was assessed using incidence rates from our cancer registry based on local population. RESULTS: Phenocopies constituted up to 24% of tests on women with breast cancer after the identification of the mutation in the proband. The standardised incidence ratio for women who tested negative for the BRCA1/BRCA2 family mutation was 5.3 for all relatives, 5.0 for all first-degree relatives (FDRs) and 3.2 (95% confidence interval 2.0 to 4.9) for FDRs in whose family all other cases of breast and ovarian cancer could be explained by the identified mutation. 13 of 107 (12.1%) FDRs with breast cancer and no unexplained family history tested negative. CONCLUSION: In high-risk families, women who test negative for the familial BRCA1/BRCA2 mutation have an increased risk of breast cancer consistent with genetic modifiers. In light of this, such women should still be considered for continued surveillance.

Adult↗
PubMed2006

Risk of hospitalization during influenza season among a cohort of patients with congestive heart failure.

It is uncertain whether hospitalization among patients with congestive heart failure (CHF) increases during the influenza season. This retrospective cohort study used influenza surveillance data from the United States (1986-1987 to 1990-1991), clinical information from the Studies of Left Ventricular Dysfunction (SOLVD) database, and daily temperature data from the National Climatic Data Center to assess the effect of influenza season on hospitalizations in this cohort of patients. The overall hospitalization rate was higher during influenza seasons compared to non-influenza seasons [relative risk (RR) 1.08, 95% confidence interval (CI) 1.01-1.16]. Multivariable Cox modelling revealed an adjusted hazard ratio (HR) of 1.11 for hospitalization during the influenza season (95% CI 1.03-1.20, P=0.005). Overall death rates were also higher during influenza seasons than non-influenza seasons (RR 1.09, 95% CI 0.97-1.21), but the corresponding adjusted HR for death was not significant (HR 1.01, 95% CI 0.98-1.24, P=0.11). Patients with CHF have a greater risk of hospitalization during the influenza season than in the non-influenza season, supporting the current belief that patients with CHF should be regarded as a high-risk group.

Cohort Studies↗
PubMed2006

Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth and scleroblasts differentiation and function.

The zebrafish caudal fin provides a simple model to study molecular mechanisms of dermal bone regeneration. We previously showed that misexpression of Bone morphogenetic protein 2b (Bmp2b) induces ectopic bone formation within the regenerate. Here we show that in addition to bmp2b and bmp4 another family member, bmp6, is involved in fin regeneration. We further investigated the function of BMP signaling by ectopically expressing the BMP signaling inhibitor Chordin which caused: (1) inhibition of regenerate outgrowth due to a decrease of blastema cell proliferation and downregulation of msxb and msxC expression and (2) reduced bone matrix deposition resulting from a defect in the maturation and function of bone-secreting cells. We then identified targets of BMP signaling involved in regeneration of the bone of the fin rays. runx2a/b and their target col10a1 were downregulated following BMP signaling inhibition. Unexpectedly, the sox9a/b transcription factors responsible for chondrocyte differentiation were detected in the non-cartilaginous fin rays, sox9a and sox9b were not only differentially expressed but also differentially regulated since sox9a, but not sox9b, was downregulated in the absence of BMP signaling. Finally, this analysis revealed the surprising finding of the expression, in the fin regenerate, of several factors which are normally the signatures of chondrogenic elements during endochondral bone formation although fin rays form through dermal ossification, without a cartilage intermediate.

Animals↗
PubMed2006

A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis.

BACKGROUND: Thyroid dysgenesis is the most frequent cause of congenital hypothyroidism (CH), and its genetic basis is largely unknown. Hitherto, two mutations in the human thyroid transcription factor 2 (TTF-2) gene have been described in unrelated cases of CH with cleft palate, spiky hair, variable choanal atresia, and complete thyroid agenesis. Here, we describe a novel TTF-2 mutation in a female child resulting in syndromic CH in the absence of thyroid agenesis. RESULTS: The index case is homozygous for an arginine to cysteine mutation (R102C) of a highly conserved residue within the forkhead, DNA binding domain of TTF-2. Her consanguineous, heterozygous parents are unaffected, and the mutation was not detected in 100 control chromosomes. Consonant with its location, the R102C mutant TTF-2 protein showed loss of DNA binding and was transcriptionally inactive. CH in the proposita was associated with cleft palate, spiky hair, and bilateral choanal atresia. However, radiological studies showed the presence of thyroid tissue in a eutopic location. CONCLUSION: Our findings indicate that human thyroid development can occur despite loss of TTF-2 function and suggest that TTF-2 gene defects should also be considered in cases of syndromic CH without total athyreosis.

Amino Acid Sequence↗
PubMed2006

A role for vector-independent transmission in rodent trypanosome infection?

Within host-pathogen systems where vector-borne transmission is the primary route of infection, little or no attention has been paid to the relative importance of secondary or alternative routes of transmission. Here, by contrast, we report the results from a controlled longitudinal field-scale experiment in which the prevalence of fleas (Siphonaptera) was manipulated and the occurrence and distribution of a flea-borne protozoan (Trypanosoma (Herpetosoma) microti) in a natural field vole (Microtus agrestis) population was monitored over a 2-year period. A non-systemic insecticide was applied to individual voles within two treatment grids and the prevalences of fleas and of T. microti were monitored on these and on two control grids. Blood samples were taken from all voles and PCR-based methods used to determine infection status. Insecticidal treatment was highly effective at reducing overall flea prevalence and recaptured animals (treated ca. 4 weeks previously) were very rarely infested (ca. 3%, compared with 50-70+% normally). On the other hand, the probability of trypanosome infection was reduced in treated animals on experimental grids to only around one-third of that normally observed. This suggests that direct, as opposed to flea-borne, transmission may not only occur, it may also be of epidemiological importance. The possibility that the importance of such transmission routes may have been underestimated in 'vector-borne' infections more generally is discussed.

Animals↗
PubMed2006

Multiple vaccine and pyridostigmine interactions: effects on EEG and sleep in the common marmoset.

Following active service during the 1990/1991 Gulf conflict, a number of UK and US veterans presented with a diverse range of symptoms, collectively known as Gulf Veterans' Illnesses (GVI). The administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (PB), given to Armed Forces personnel during the Gulf conflict has been implicated as a possible factor in the aetiology of these illnesses. The possibility that long-term health effects may result from the administration of these vaccines (anthrax, pertussis, plague, yellow fever, polio, typhoid, tetanus, hepatitis B, meningococcal meningitis and cholera) and/or PB, have been investigated using a non-human primate model, the common marmoset. This paper reports the results from two aspects of the study, brain electrical activity (EEG, collected during performance of a touchscreen mediated discrimination task) and sleep. There were no marked long-term changes in EEG or sleep patterns that could be attributed to vaccines and/or PB administration. The changes that were detected were predominantly time related and independent of treatment. Where statistical differences were detected between treatments, the magnitudes of the difference were relatively minor and therefore not regarded as having long term biological significance.

Animals↗
PubMed2006

Outbreaks of waterborne infectious intestinal disease in England and Wales, 1992-2003.

We reviewed the epidemiological and microbiological characteristics of 89 reported outbreaks of waterborne infectious intestinal disease affecting 4321 people in England and Wales over the period 1992-2003. Public water supplies were implicated in 24 outbreaks (27%), private water supplies in 25 (28%), swimming pools in 35 (39%) and other sources in five outbreaks (6%). Cryptosporidium was implicated in 69% of outbreaks, Campylobacter sp. in 14%, Giardia in 2%, E. coli O157 in 3% and Astrovirus in 1%. From 2000, there was a consistent decline in the number of outbreaks of waterborne disease associated with public water supplies. The incidence rate of outbreaks in recipients of private water supplies may be as high as 35 times the rate in those receiving public water supplies (1830 vs. 53 per million population). Private water suppliers need to be aware of the importance of adequate treatment and the prevention of faecal contamination of storage water. Swimming-pool operators need to ensure chlorination and in particular adequate filtration measures are in place.

Communicable Diseases↗
PubMed2006

Charmonium Decays of Y(4260), psi(4160), and psi(4040).

Using data collected with the CLEO detector operating at the CESR e+e- collider at sqrt[s]=3.97-4.26 GeV, we investigate 15 charmonium decay modes of the psi(4040), psi(4160), and Y(4260) resonances. We confirm, at 11 sigma significance, the BABAR Y(4260)-->pi+pi- J/psi discovery, make the first observation of Y(4260)--> pi(0)pi(0) J/psi (5.1 sigma), and find the first evidence for Y(4260)-->K+K- J/psi(3.7 sigma). We measure e+e- cross sections at sqrt[s]=4.26 GeV as sigma(pi+pi- J/psi)=58(+12)(-10)+/-4 pb, sigma(pi(0)pi(0) J/psi)=23(+12)(-8)+/-1 pb, and sigma(K+K- J/psi)=9(+9)(-5)+/-1 pb, in which the uncertainties are statistical and systematic, respectively. Upper limits are placed on other decay rates from all three resonances.

Journal Article↗
PubMed2006

Experimental limits on weak annihilation contributions to decays.

We present the first experimental limits on high-q2 contributions to charmless semileptonic decays of the form expected from the weak annihilation (WA) decay mechanism. Such contributions could bias determinations of /Vub/ from inclusive measurements of B-->Xulupsilon. Using a wide range of models based on available theoretical input we set a limit of GammaWA/Gammab-->u<7.4% (90% confidence level) on the WA fraction, and assess the impact on previous inclusive determinations of /Vub/.

Journal Article↗
PubMed2006

Dielectron widths of the Gamma(1S,2S,3S) resonances.

We determine the dielectron widths of the Gamma(1S), Gamma(2S), and Gamma(3S) resonances with better than 2% precision by integrating the cross section of e+e- -->Gamma over the e+e- center-of-mass energy. Using e+e- energy scans of the Gamma resonances at the Cornell Electron Storage Ring and measuring Gamma production with the CLEO detector, we find dielectron widths of 1.252+/-0.004(sigma(stat))+/-0.019(sigma(syst)) keV, 0.581+/-0.004+/-0.009 keV, and 0.413+/-0.004+/-0.006 keV for the Gamma(1S), Gamma(2S), and Gamma(3S), respectively.

Journal Article↗
PubMed2006

Measurement of sigma(e+e- -->psi(3770)-->hadrons) at Ec.m.=3773 MeV.

We measure the cross section for e+e- -->psi(3770) -->hadrons at Ec.m.=3773 MeV to be (6.38+/-0.08(+0.41)(-0.30) nb using the CLEO detector at the CESR e+e- collider. The difference between this and the e+e- -->psi(3770) -->DD cross section at the same energy is found to be (-0.01+/-0.08(+0.41)(-0.30) nb. With the observed total cross section, we extract Gamma(ee)(psi(3770))=(0.204+/-0.003(+0.041)(-0.027) keV. Uncertainties shown are statistical and systematic, respectively.

Journal Article↗
PubMed2006

Observation of psi(3770) --> pi pi J/psi and measurement of Gamma ee[psi(2S)].

We observe signals for the decays psi(3770) --> XJ/psi from data acquired with the CLEO detector operating at the CESR e+ e- collider with square root of s = 3773 MeV. We measure the following branching fractions Beta(psi(3770) --> XJ/psi and significances: (189 +/- 20 +/- 20) x 10(-5) (11.6sigma) for X = pi+ pi-, (80 +/- 25 +/- 16) x 10(-5) (3.4sigma) for X = pi0 pi0, and (87 +/- 33 +/- 22) x 10(-5) (3.5sigma) for X = eta, where the errors are statistical and systematic, respectively. The radiative return process e+ e- --> gamma psi(2S) populates the same event sample and is used to measure Gamma ee[psi(2S)] = (2.54 +/- 0.03 +/- 0.11) keV.

Journal Article↗