PubMed Health⌕ Search

Biomedical subjects

M Allen

Publications and source records attributed to M Allen.

At least 19 recordsLinked to original sources

Decoding the ancient Greek astronomical calculator known as the Antikythera Mechanism.

The Antikythera Mechanism is a unique Greek geared device, constructed around the end of the second century bc. It is known that it calculated and displayed celestial information, particularly cycles such as the phases of the moon and a luni-solar calendar. Calendars were important to ancient societies for timing agricultural activity and fixing religious festivals. Eclipses and planetary motions were often interpreted as omens, while the calm regularity of the astronomical cycles must have been philosophically attractive in an uncertain and violent world. Named after its place of discovery in 1901 in a Roman shipwreck, the Antikythera Mechanism is technically more complex than any known device for at least a millennium afterwards. Its specific functions have remained controversial because its gears and the inscriptions upon its faces are only fragmentary. Here we report surface imaging and high-resolution X-ray tomography of the surviving fragments, enabling us to reconstruct the gear function and double the number of deciphered inscriptions. The mechanism predicted lunar and solar eclipses on the basis of Babylonian arithmetic-progression cycles. The inscriptions support suggestions of mechanical display of planetary positions, now lost. In the second century bc, Hipparchos developed a theory to explain the irregularities of the Moon's motion across the sky caused by its elliptic orbit. We find a mechanical realization of this theory in the gearing of the mechanism, revealing an unexpected degree of technical sophistication for the period.

Journal Article↗

Quantification of mtDNA mixtures in forensic evidence material using pyrosequencing.

Analysis of mtDNA variation using Sanger sequencing does not allow accurate quantification of the components of mtDNA mixtures. An alternative method to determine the specific mixture ratios in samples displaying hetero-plasma, consisting of DNA contributions from several individuals, or containing contamination would therefore be valuable. A novel quantification system for mtDNA mixture analysis has been developed based on pyrosequencing technology, in which the linear relationship between incorporated nucleotides and released light allows quantification of the components of a sample. Within five polymerase chain reaction fragments, seven variable positions in the mtDNA control and coding region were evaluated using this quantification analysis. For all single nucleotide polymorphisms quantified in this study, a linear relationship was observed between the measured and expected mixture ratios. This mtDNA quantification assay is an easy to use, fast and accurate quantification system, with the ability to resolve and interpret major and minor mtDNA components in forensic mixture samples.

DNA Fingerprinting↗

Nuclear and mitochondrial DNA quantification of various forensic materials.

Due to the different types and quality of forensic evidence materials, their DNA content can vary substantially, and particularly low quantities can impact the results in an identification analysis. In this study, the quantity of mitochondrial and nuclear DNA was determined in a variety of materials using a previously described real-time PCR method. DNA quantification in the roots and distal sections of plucked and shed head hairs revealed large variations in DNA content particularly between the root and the shaft of plucked hairs. Also large intra- and inter-individual variations were found among hairs. In addition, DNA content was estimated in samples collected from fingerprints and accessories. The quantification of DNA on various items also displayed large variations, with some materials containing large amounts of nuclear DNA while no detectable nuclear DNA and only limited amounts of mitochondrial DNA were seen in others. Using this sensitive real-time PCR quantification assay, a better understanding was obtained regarding DNA content and variation in commonly analysed forensic evidence materials and this may guide the forensic scientist as to the best molecular biology approach for analysing various forensic evidence materials.

DNA Fingerprinting↗

Pacemakers and implantable cardioverter defibrillators.

An increasing number of patients are now treated cardiac pacemakers and implantable cardioverter defibrillators and the technology of these is constantly changing. It is vital to have a good understanding of how they function and what the real risks are. Understanding how the device should work when functioning normally, and the possible effects of electromagnetic interference, is paramount to their safe management in the peri-operative period. Knowing when a device should be disabled or reprogrammed requires careful consideration. Information from the patient's pacemaker clinic should be sought whenever possible and can be invaluable. In addition, the Medicines Healthcare products Regulatory Agency have published the first set of UK guidelines on the management of implantable devices in the presence of surgical diathermy and this will undoubtedly provide a firm foundation on which anaesthetists can base much of their practice.

Defibrillators, Implantable↗

Management of twin-twin transfusion syndrome in pregnancies with iatrogenic detachment of membranes following therapeutic amniocentesis and the role of interim amniopatch.

OBJECTIVE: Detachment of membranes may occur after therapeutic amniocentesis for twin-twin transfusion syndrome (TTTS). Subsequent amniocenteses or endoscopic fetal therapy may be hindered or made altogether impossible by this complication. The purpose of this study was to describe our experience in the assessment and management of TTTS patients with iatrogenic detached membranes (IDM). METHODS: Patients with IDM referred for fetal surgery for TTTS were considered ineligible for standard surgery and were offered different alternatives, including expectant management, serial amniocentesis, or an attempt at surgery with or without prior amniopatch. Pregnancy outcomes were compared between surgical and non-surgical patients. RESULTS: Nine hundred and forty-four patients with a diagnosis of TTTS were referred between July 1997 and December 2004, of whom 322 (34.1%) had a prior therapeutic amniocentesis. Twenty-six of the 322 patients (8%) had IDM. Ten patients opted to be managed with subsequent amniocenteses, two of which had an amniopatch. One patient had voluntary interruption of pregnancy. Fifteen patients underwent surgery, 10 of whom underwent an amniopatch. Overall, resealing of membranes occurred in 8/12 (66%) patients treated with an amniopatch. Survival of at least one fetus was greater in patients treated surgically with or without an amniopatch (12/15, 80% vs. 4/11, 36%, P = 0.04). CONCLUSION: Membrane detachment is an important complication of therapeutic amniocentesis in the treatment of TTTS. Although successful treatment of IDM can be achieved with an interim amniopatch, this alternative is not without risks. Therapeutic amniocenteses should be discouraged in patients considering endoscopic fetal surgery for TTTS.

Amniocentesis↗

Statistical processing of large image sequences.

The dynamic estimation of large-scale stochastic image sequences, as frequently encountered in remote sensing, is important in a variety of scientific applications. However, the size of such images makes conventional dynamic estimation methods, for example, the Kalman and related filters, impractical. In this paper, we present an approach that emulates the Kalman filter, but with considerably reduced computational and storage requirements. Our approach is illustrated in the context of a 512 x 512 image sequence of ocean surface temperature. The static estimation step, the primary contribution here, uses a mixture of stationary models to accurately mimic the effect of a nonstationary prior, simplifying both computational complexity and modeling. Our approach provides an efficient, stable, positive-definite model which is consistent with the given correlation structure. Thus, the methods of this paper may find application in modeling and single-frame estimation.

Algorithms↗

Alternative splicing of IL-24 in melanocytes by deletion of exons 3 and 5.

Two novel interleukin-24 (IL-24) splice variants were identified in normal human melanocytes by sequencing cloned polymerase chain reaction (PCR) products that are not expressed in metastatic melanoma. These gene products have been generated by differential skipping of exons 3 (IL-24 delE3) and 5 (IL-24 delE5). IL-24 delE3 has limited sequence identity to the IL-24-interacting protein mda-7s, and IL-24 delE5 is homologous to IL-24.

Alternative Splicing↗

Diabetes care provision and glycaemic control in Northern Ireland: a UK regional audit.

AIMS: To assess the care received, compared to national guidelines, and to investigate factors associated with glycaemic control in children and adolescents with type 1 diabetes attending clinics in Northern Ireland. METHODS: An audit of the care provided to all patients attending 11 paediatric diabetes clinics commenced in 2002. A research nurse interviewed 914 patients completing a questionnaire recording characteristics, social circumstances, and aspects of diabetes management, including the monitoring of complications and access to members of the diabetes team. Glycaemic control was measured by glycosylated haemoglobin (HbA1c), determined at a DCCT aligned central laboratory. RESULTS: The average HbA1c concentration was 8.8% (SD 1.5%), with 20% of patients achieving recommended HbA1c levels of less than 7.5%. In the year prior to the audit, 76% of patients were reviewed by a diabetes specialist nurse and 42% were tested for microalbuminuria. After adjustment for confounding factors, better glycaemic control was identified, particularly in patients who had attended exactly four diabetes clinics in the previous year, were members of the patient association Diabetes UK, and lived with both natural parents. CONCLUSIONS: In Northern Ireland only a minority of patients achieved recommended HbA1c levels. Furthermore, children and adolescents with diabetes were reviewed by fewer specialists and were less intensively monitored for microvascular complications than recommended. There was evidence of better control in children who were members of Diabetes UK, suggesting that parental attitude and involvement could lead to benefits.

Adolescent↗

Internationalization of higher education: potentials and pitfalls for nursing education.

BACKGROUND: Internationalization, an integral part of strategic planning initiatives in universities around the world, is occurring within the context of globalization. As we move toward greater internationalization in nursing education, we must understand the ideologies that currently underpin globalization and their fit with the vision and mission of nursing. AIM: To outline the current debates surrounding internationalization and globalization and their potential consequences for universities. METHODS: The historical and current interest in internationalization and globalization are reviewed briefly in order to set the context for this discussion. CONCLUSIONS: What emerges from an analysis of current internationalization directions is the complexity of the relationship between internationalization and the conflicting ideologies underpinning globalization. Nursing can play a key role within universities to ensure that varying viewpoints are debated and the implications of varying internationalization decisions are understood.

Cultural Diversity↗

Spatial uniformity of laser-accelerated ultrahigh-current MeV electron propagation in metals and insulators.

The evolution of laser-generated MeV, MA electron beams propagating through conductors and insulators has been studied by comparing measurement and modeling of the distribution of MeV protons that are sheath accelerated by the propagated electrons. We find that electron flow through metals is uniform and can be laser imprinted, whereas propagation through insulators induces spatial disruption of the fast electrons. Agreement is found with material dependent modeling.

Journal Article↗

Isochoric heating of solid-density matter with an ultrafast proton beam.

A new technique is described for the isochoric heating (i.e., heating at constant volume) of matter to high energy-density plasma states (>10(5) J/g) on a picosecond time scale (10(-12)sec). An intense, collimated, ultrashort-pulse beam of protons--generated by a high-intensity laser pulse--is used to isochorically heat a solid density material to a temperature of several eV. The duration of heating is shorter than the time scale for significant hydrodynamic expansion to occur; hence the material is heated to a solid density warm dense plasma state. Using spherically shaped laser targets, a focused proton beam is produced and used to heat a smaller volume to over 20 eV. The technique described of ultrafast proton heating provides a unique method for creating isochorically heated high-energy density plasma states.

Journal Article↗

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials.

This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freund's caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection.

AIDS Vaccines↗

Analysis of the time course and prognostic factors determining toxicity due to infused fluorouracil.

This study used a prospectively managed clinical database in order to identify 1470 patients with gastrointestinal cancers receiving protracted venous infusion (PVI) fluorouracil (5FU). It aimed to determine the time course of toxicity due to PVI 5FU and to analyse factors predicting toxicity. The initial development of stomatitis occurred more rapidly than diarrhoea or palmar plantar erythema (PPE). The percentage of patients with National Cancer Institute Common Toxicity Criteria (CTC) grade 2 or worse PPE peaked at 9% between weeks 8 and 17, whereas this peak occurred earlier for stomatitis and diarrhoea. The development of CTC grade 1 toxicity in the first 28 days after commencement of chemotherapy was classified as early grade 1 toxicity. Multivariate Cox regression analysis showed that female sex, better performance status, elevated bilirubin, early grade 1 PPE and early grade 1 diarrhoea were independent prognostic factors for the development of CTC grade 2 or worse PPE (P<0.01). Female sex, increased age, elevated alanine transaminase and urea and early grade 1 PPE were significant independent prognostic factors for the development of CTC grade 2 or worse stomatitis (P<0.01). Early CTC grade 1 diarrhoea predicted CTC grade 2 or worse diarrhoea (P<0.01). Older, female patients with good performance status and impaired liver and renal function who develop early grade 1 PPE alone or in combination with diarrhoea are at highest risk of subsequently developing grade 2 or worse PPE or stomatitis during treatment with PVI 5FU. Reduction of infused 5FU dose should be considered for these patients. Such an approach could both reduce severe toxicity owing to chemotherapy and minimise treatment delays, and should be evaluated prospectively.

Adult↗

Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer.

This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n=30, CT alone n=6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m(-2) day(-1) for 12 weeks) with mitomycin C (MMC) (7 mg m(-2) i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m(-2) day(-1) and concomitant pelvic radiotherapy 45 Gy in 25 fractions was commenced followed by 5.4-9 Gy boost to tumour bed. Surgery was planned 6 weeks after chemoradiation. Postoperatively, patients received 12 weeks of MMC and 5-FU at the same preoperative doses. Between January 99 and August 01, 36 eligible patients were recruited. Median age was 63 years (range=40-85). Following neoadjuvant chemotherapy, radiological tumour response was 27.8% (one CR and nine PRs) and no patient had progressive disease. In addition, 65% of patients had a symptomatic response including improvement in diarrhoea/constipation (59%), reduced rectal bleeding (60%) and diminished pelvic pain/tenesmus (78%). Following chemoradiation, tumour regression occurred in 80.6% (six CRs and 23 PRs; 95% CI=64-91.8%) and only one patient still had an inoperable tumour. R0 resection was achieved in 28 patients (82%). When compared with initial clinical staging, the pathological downstaging rate in T and/or N stage was 73.5% and pathological CR was found in one patient. Neoadjuvant systemic chemotherapy as a prelude to synchronous chemoradiation can be administered with negligible risk of disease progression and produces considerable symptomatic response with associated tumour regression.

Adult↗

Rapid access multidisciplinary lymph node diagnostic clinic: analysis of 550 patients.

Lymphadenopathy is common, affecting patients of all ages. The current referral pattern for investigating patients with lymphadenopathy varies widely with no universally practised pathway. Our institution set up a lymph node diagnostic clinic (LNDC) accepting direct referrals from primary care physicians. Details of clinical presentation and investigations were recorded prospectively. Between December 1996 and July 2001, 550 patients were referred (M: 203; F:347). The median age was 40 years (range 14-90). The median time between initial referral and the first clinic visit was 6 days. Of 95 patients diagnosed to have malignant diseases, the median time from the first clinic visit to reaching malignant diagnosis was 15 days. Multivariate logistic regression analysis identified five significant predictors for malignant nodes: male gender (risk ratio (RR)=2.72; 95% confidence interval (CI): 1.63-4.56), increasing age (RR=1.05; 95% CI: 1.04-1.07), white ethnicity (RR=3.01; 95% CI: 1.19-7.6) and sites of lymph nodes: supraclavicular region (RR=3.72; 95% CI: 1.52-9.12) and > or = 2 regions of lymph nodes (RR=6.41; 95% CI: 2.82-14.58). Ultrasound and fine-needle aspiration cytology of palpable lymph nodes were performed in 154 and 289 patients, respectively. An accuracy of 97 and 84% was found, respectively. In conclusion, a multidisciplinary lymph node diagnostic clinic enables a rapid, concerted approach to a common medical problem and patients with malignant diseases were diagnosed in a timely fashion.

Adult↗

Mitomycin C, carboplatin and protracted venous infusion 5-fluorouracil in advanced oesophago-gastric and pancreatic cancer: results of two phase II studies.

Cisplatin is an active palliative chemotherapy agent in advanced upper gastrointestinal cancer, but it is associated with significant non-haematological toxicity. Substitution of cisplatin by carboplatin in combination chemotherapy regimens may reduce these adverse effects. These two phase II studies evaluated the efficacy and toxicity of the combination of mitomycin C (MMC) 7 mg/m2 q 6 weekly, carboplatin area under the concentration-time curve 5 mg/ml/min q 3 weekly and protracted venous infusion 5-fluorouracil (5FU) 300 mg/m2/day (McarboF) in advanced upper gastrointestinal cancer. Between October 1998 and June 2000, 31 patients were enrolled in the studies, 23 patients in the oesophago-gastric study and eight patients in the pancreatic study. Although non-haematological toxicity was modest, both protocols were closed prematurely because of excessive haematological toxicity and frequent treatment delays. The overall incidence of grade 3/4 neutropenia and thrombocytopenia was 39 and 52%, respectively. The McarboF combination showed significant activity with an overall response rate of 52% in advanced oesophago-gastric cancer. Palliative benefit was also evident with improvement in symptoms of pain and weight loss in over 79 and 50% of patients in the oesophago-gastric study and pancreatic study, respectively. Median overall survival times were 10.6 and 6.6 months for patients with oesophago-gastric and pancreatic cancer, respectively. The McarboF regimen showed promising activity in advanced upper gastrointestinal cancer, with modest non-haematological side-effects. This combination merits further evaluation with modification of the dose and schedule of carboplatin and MMC in order to reduce the severity of haematological toxicity.

Adult↗