Circadian clock mechanism driving mammalian photoperiodism.

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization in plants. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that long photoperiods induce the circadian transcription factor BMAL2, in the pars tuberalis of the pituitary, and triggers summer biology through the eyes absent/thyrotrophin (EYA3/TSH) pathway. Conversely, long-duration melatonin signals on short photoperiods induce circadian repressors including DEC1, suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock-pituitary epigenetic pathway interactions form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates.

Role of reconstructive surgery in the management of head and neck cancer: a national outcomes analysis of 11,841 reconstructions.

BACKGROUND: The quality of head and neck cancer reconstruction in England is not known. Hospital administrative data provides details of treatment within the English National Health Service and may be used for national outcomes analysis. METHODS: An algorithm for identifying head and neck surgery with flap-based reconstruction from administrative data was constructed and validated against information from three cancer units. The validated algorithm was applied to 2003-2013 national activity. RESULTS: The algorithm was 91% sensitive and over 99% specific. Its application to administrative data identified 11,841 patients and demonstrated an increase of 52% in reconstruction-containing head and neck cancer surgery in the past decade. There were 7776 males and mean treatment age was 62 years. Oral cavity was the commonest primary site (n = 7567; 64%) and 7575 patients (64%) underwent primary surgery. The commonest procedure was floor-of-mouth excision (n = 3614) and 9749 patients had a neck dissection. The most commonly used flap was the radial forearm (n = 4429). Flap failure occurred in 496 (4.2%) patients. It increased the mean length of stay from 22 to 41 days (P < 0.00001), and the odds ratio of in-hospital death to 2.37 [95% confidence interval 1.66-3.38; P < 0.0001]. Lethality of reconstructive failure was not uniform and was highest when a pharyngolaryngeal flap failed. CONCLUSIONS: Reconstructive surgery is central to the multidisciplinary management of head and neck cancer. Its quality directly influences patient morbidity and survival. We recommend that analysis of hospital administrative data should be periodically carried out as part of an over-arching quality assurance programme and, particularly for pharyngolaryngeal reconstructions, surgery should be undertaken in units with the best reconstructive outcomes.

A comparison of the patient and surgeon opinion on the long-term aesthetic outcome of reduction mammaplasty: have we improved over 15 years?

In 1996 we published a study evaluating the difference between patient and surgeon opinion on the aesthetic outcome of reduction mammaplasty (see Ref. 1). The patients rated the aesthetic outcome of their surgery as significantly higher than the consultant panel. The surgical panel suggested scope for improvement. Areas of dissatisfaction were poor scarring, high placement of the nipple areola complex and high rates of revision surgery. Fifteen years on, the same team has regrouped to repeat this assessment. In 1996 the consultants scored their own patient results. In 2011 they graded the results of their former trainee who has modified her operative technique to address aesthetic problems highlighted in the first study. Forty-four patients attended a review clinic at least one year post reduction mammaplasty. Patient scored their satisfaction using the original questionnaire employed in 1996. The cohort were photographed and their images graded blindly by the original surgical panel. Statistical analysis was performed by the original statistician. The patients graded aesthetic aspects of body harmony, breast mound appearance, nipple areolar complex appearance and post-operative scarring significantly more positively (p<0.01) than both the 1996 patient cohort and surgical panel. The consultant panel showed a trend for more positive grades for all aesthetic features assessed versus their previous views but this was only significant for breast mound symmetry. They expressed that there was a decrease in post-operative breast ptosis (p<0.04) and improvement in the nipple areolar complex position (p=0.02). The rate of revision surgery has decreased from 53% to 16% between the studies. In keeping with clinical audit, outcomes have been assessed and modifications implemented to address aesthetic concerns. Assessment of outcomes following the modifications demonstrates a trend for increased patient and surgeon satisfaction. Patient satisfaction however still exceeds that of the surgeons.

The economic viability of breast reconstruction in the UK: comparison of a single surgeon's experience of implant; LD; TRAM and DIEP based reconstructions in 274 patients.

A retrospective audit was performed of patients undergoing breast reconstruction under the care of the senior author from 2000 to 2007. We documented reconstruction type, length of stay and total number of revisions. Income to the trust based on the 2008/9 HRG codes along with any "top ups" was also recorded. This was compared to calculations of cost to the trust of performing each reconstruction. 274 patients had 278 primary reconstructions and a further 366 revisions. Only patients with a minimum one-year's follow-up were included (mean 3 years). This included 68 DIEPs'; 39 TRAMs'; 98 LDs'; and 73 implant reconstructions. The median length of stay for implant based reconstruction was 4 days; 9 for LD flaps; 11 for TRAMs' and 8 for DIEPs'. This was significantly shorter for the implant group compared to other reconstructions (P<0.001). The mean number of surgical revisions was 1.5 for implant reconstructions; 1.6 for LDs; 0.9 for TRAMs' and 0.8 for DIEPs'. There were significantly more revisions of implant reconstructions than DIEPs (P=0.037) and significantly more revisions of LDs compared to TRAM and DIEPs' (P=0.012 and 0.0023). In our study, the cost of an LD, TRAM or DIEP reconstruction including both primary surgery and any revisions was similar, and while at an average of three years, the implant reconstruction remains cheaper, that patient will still require more revisions, and if followed up enough will lose this small financial benefit. Furthermore, the difference is small (£8034 for implants vs. £10910 for DIEPs), and it could be argued this is justified by the increased patient satisfaction and cosmetic outcome. Finally we highlight several areas of financial inequality, including insufficient remuneration for providing individual operations, the lack of payment for performing more than one procedure at the same time and lack of payment for bilateral procedures.

Assessment of the functionality of genome-wide canine SNP arrays and implications for canine disease association studies.

Domestic dogs share a wide range of important disease conditions with humans, including cancers, diabetes and epilepsy. Many of these conditions have similar or identical underlying pathologies to their human counterparts and thus dogs represent physiologically relevant natural models of human disorders. Comparative genomic approaches whereby disease genes can be identified in dog diseases and then mapped onto the human genome are now recognized as a valid method and are increasing in popularity. The majority of dog breeds have been created over the past few hundred years and, as a consequence, the dog genome is characterized by extensive linkage disequilibrium (LD), extending usually from hundreds of kilobases to several megabases within a breed, rather than tens of kilobases observed in the human genome. Genome-wide canine SNP arrays have been developed, and increasing success of using these arrays to map disease loci in dogs is emerging. No equivalent of the human HapMap currently exists for different canine breeds, and the LD structure for such breeds is far less understood than for humans. This study is a dedicated large-scale assessment of the functionalities (LD and SNP tagging performance) of canine genome-wide SNP arrays in multiple domestic dog breeds. We have used genotype data from 18 breeds as well as wolves and coyotes genotyped by the Illumina 22K canine SNP array and Affymetrix 50K canine SNP array. As expected, high tagging performance was observed with most of the breeds using both Illumina and Affymetrix arrays when multi-marker tagging was applied. In contrast, however, large differences in population structure, LD coverage and pairwise tagging performance were found between breeds, suggesting that study designs should be carefully assessed for individual breeds before undertaking genome-wide association studies (GWAS).

Pharyngolaryngectomy using a free jejunal graft: a new anastomosis technique.

We describe a technique of staple anastomosis for pharyngolaryngeal reconstruction using a free jejunal graft. Stapled anastomosis can be applied to both the upper and lower pharyngeal and oesophageal repair. Our series of 37 stapled anastomosis developed no post operative leaks. This technique allows an easier method for inferior anastomosis low down in the upper mediastinum where access is often difficult. Swallowing was established in all patients. Primary puncture into oesophagus below the anastomosis, gives good results with a low stricture rate of 11% all of which resolved with a single subsequent dilatation.

Tibial stress fracture as a complication of free-fibula vascularised graft for mandibular reconstruction.

The free vascularised fibula graft is used for a variety of reconstructive procedures and is frequently associated with donor site morbidity. Non-traumatic stress fracture to the tibia following a vascularised free-fibula graft is an uncommon but important complication. The diagnosis may be missed if radiological "stress views" of a possible fracture site are not performed, which may result in its underreporting. The authors report a case in which the aetiology, diagnosis and management recommendations are presented for discussion.

A prospective, randomized, double-blind trial of the use of fibrin sealant for face lifts.

Fibrin sealant imitates the final phase of the blood coagulation process. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin, which is then cross-linked by factor XIIIa, creating a mechanically stable fibrin network. This fibrin network is thought to reduce the amount of postoperative bleeding by sealing capillary vessels and allowing raw operative surfaces to adhere. The authors conducted a prospective, double-blind, randomized, controlled trial on the use of fibrin sealant in 20 consecutive patients undergoing bilateral face lifts by the same surgeon. Each patient was randomized for the use of fibrin sealant on either the right or the left side with the contralateral side acting as the control. Total drainage was recorded on each side for 24 hours before drains were removed. The age range of the patients in the trial (all of whom were women) was 44 to 70 years (mean, 55). The side treated with fibrin glue had a median drainage of 10 ml and the control side 30 ml. The Wilcoxon signed rank test shows a significant difference in drainage between sides (p = 0.002). The reduction in postoperative drainage could also reduce pain and bruising, increasing patient satisfaction with this procedure. The need for drains may also be obviated.

Vertebrate exon trapping methods: implications for transcript mapping with mosquito DNA.

Exon trapping methods have played an important role in the development of transcript maps. In one in vivo vertebrate method, exons in a genomic DNA clone are transcribed, and they are recovered without any a priori information on the nature of the expressed transcript. The only requirement is that the genomic DNA clone contains exons separated by intervening introns that are removed by splicing during mRNA transcription and that the splice donor and acceptor site sequences follow those used by vertebrates. It is not known whether invertebrate splice donor and acceptor sites from genes that contain short introns will be processed correctly using an in vivo vertebrate exon trapping method. In this report, an analysis of mosquito splice sites using software designed to identify exons in genomic DNA sequence suggested that the vertebrate exon trapping method could recognize mosquito introns and exons. When a mosquito genomic DNA clone containing the D7 gene was tested experimentally, this method failed to recognize and process small introns (< 63 bp) faithfully. In spite of this failure, exons and exon fragments were recovered. The implications of these findings and their application to map-based positional cloning in mosquito genomics is discussed.

A local anaesthetic technique for endoscopic carpal tunnel release.

A local anaesthetic technique for endoscopic carpal tunnel release is described. This accurately and rapidly blocks median and ulnar nerves in the distal forearm. It avoids the infiltration of local anaesthetic solution at the operation site, a technique which may render the endoscopic view unsatisfactory.

A comparison of the patient and surgeon opinion on the long-term aesthetic outcome of reduction mammaplasty.

The aim of this study was to assess the difference in opinion between patients and surgeons regarding the aesthetic outcome of reduction mammaplasty. A total of 34 women, who were more than 1 year post surgery, attended an outpatient clinic to assess their opinion of the aesthetic outcome of their breast reduction. A questionnaire was used to standardise their responses. Photographic slides were taken to record the frontal, left oblique and recumbent view of their torso. These slides were assessed by four consultant plastic surgeons who completed the same questionnaire, and were blinded as to the surgeon and patient. The majority of patients rated the aesthetic outcomes of their surgery significantly higher than the consultants. Scarring was the most frequent cause of dissatisfaction for both surgeons and patients. The consultants considered the scarring following Lejour reduction to be significantly better than that following the inferior mound reduction. The nipple was considered to be too high on the breast by 12% of women but they did not request correction of this. However, consultants thought this was a problem in 27% of cases. The aesthetic outcome of reduction mammaplasty was acceptable to the patients although surgical assessment indicates that there is scope for improvement. The main area of aesthetic dissatisfaction remains the postoperative scarring.

Poly(ethylene glycol) limits of detection using internal matrix-assisted laser desorption/ionization Fourier transform mass spectrometry.

Detection limits of poly(ethylene glycol) were examined in the mass range 2000-6000 Da. Using an aerospray sample deposition technique, highly uniform sample surfaces were produced. This method allows signal averaging of spectra from up to 400 shots on the same sample spot. It is found that, as the material available for desorption is decreased, the overall average sample consumption per shot is decreased. Experimentally determined detection limits of 40 and 280 fmol (based on the average molecular masses of 2000 and 6000) were found for PEG 2000 and PEG 6000, respectively. The sample spectra show oligomer distributions in agreement with their higher concentration counterparts. However, at the lowest signal-to-noise levels, oligomers at the extremes of the distribution are no longer detected, making the polymer distribution appear to be narrower in mass range.

Major burns in Cape Town: a modified burns score for patient triage.

Major burns equal to, or greater than, 30 per cent total body surface area (TBSA) constitute 23 per cent of the admissions to the adult burns unit in Cape Town. A retrospective review over a 28-month period identified 87 cases of major burns. This paper summarizes the epidemiology and mortality amongst this patient group over this period. Demand for treatment can exceed bed availability in the unit. The difficult issue, this raises, of patient triage in relation to the relatively limited resources is addressed and a simple modified burns score proposed for this unit. The effect this score would have in optimizing the use of our resources is demonstrated.

Advanced practice nursing: back to the future.

Advanced practice nursing has evolved during the last 25 years in important ways to become a central component of the new health care system. The quality of care and cost effectiveness of practice for various advanced practice roles has been well documented. New roles are being created as the demand-driven health care system presents opportunities for innovative practice models. It is incumbent on nursing to prove its ability to assume full accountability and responsibility so that full freedom to practice may be achieved.