Rare and declining bird species benefit most from designating protected areas for conservation in the UK.

There have been recent renewed commitments to increase the extent of protected areas to combat the growing biodiversity crisis but the underpinning evidence for their effectiveness is mixed and causal connections are rarely evaluated. We used data gathered by three large-scale citizen science programmes in the UK to provide the most comprehensive assessment to date of whether national (Sites of Special Scientific Interest) and European (Special Protection Areas/Special Areas of Conservation) designated areas are associated with improved state (occurrence, abundance), change (rates of colonization, persistence and trend in abundance), community structure and, uniquely, demography (productivity) on a national avifauna, while controlling for differences in land cover, elevation and climate. We found positive associations with state that suggest these areas are well targeted and that the greatest benefit accrued to the most conservation-dependent species since positive associations with change were largely restricted to rare and declining species and habitat specialists. We suggest that increased productivity provides a plausible demographic mechanism for positive effects of designation.

A Multipronged Comparative Study of the Ultraviolet Photochemistry of 2-, 3-, and 4-Chlorophenol in the Gas Phase.

The S1((1)ππ*) state of the (dominant) syn-conformer of 2-chlorophenol (2-ClPhOH) in the gas phase has a subpicosecond lifetime, whereas the corresponding S1 states of 3- and 4-ClPhOH have lifetimes that are, respectively, ∼2 and ∼3-orders of magnitude longer. A range of experimental techniques-electronic spectroscopy, ultrafast time-resolved photoion and photoelectron spectroscopies, H Rydberg atom photofragment translational spectroscopy, velocity map imaging, and time-resolved Fourier transform infrared emission spectroscopy-as well as electronic structure calculations (of key regions of the multidimensional ground (S0) state potential energy surface (PES) and selected cuts through the first few excited singlet PESs) have been used in the quest to explain these striking differences in excited state lifetime. The intramolecular O-H···Cl hydrogen bond specific to syn-2-ClPhOH is key. It encourages partial charge transfer and preferential stabilization of the diabatic (1)πσ* potential (relative to that of the (1)ππ* state) upon stretching the C-Cl bond, with the result that initial C-Cl bond extension on the adiabatic S1 PES offers an essentially barrierless internal conversion pathway via regions of conical intersection with the S0 PES. Intramolecular hydrogen bonding is thus seen to facilitate the type of heterolytic dissociation more typically encountered in solution studies.

Functional acetabular component position with supine total hip replacement.

Orientation of the acetabular component influences wear, range of movement and the incidence of dislocation after total hip replacement (THR). During surgery, such orientation is often referenced to the anterior pelvic plane (APP), but APP inclination relative to the coronal plane (pelvic tilt) varies substantially between individuals. In contrast, the change in pelvic tilt from supine to standing (dPT) is small for nearly all individuals. Therefore, in THR performed with the patient supine and the patient's coronal plane parallel to the operating table, we propose that freehand placement of the acetabular component placement is reliable and reflects standing (functional) cup position. We examined this hypothesis in 56 hips in 56 patients (19 men) with a mean age of 61 years (29 to 80) using three-dimensional CT pelvic reconstructions and standing lateral pelvic radiographs. We found a low variability of acetabular component placement, with 46 implants (82%) placed within a combined range of 30° to 50° inclination and 5° to 25° anteversion. Changing from the supine to the standing position (analysed in 47 patients) was associated with an anteversion change < 10° in 45 patients (96%). dPT was < 10° in 41 patients (87%). In conclusion, supine THR appears to provide reliable freehand acetabular component placement. In most patients a small reclination of the pelvis going from supine to standing causes a small increase in anteversion of the acetabular component.

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.

Why large-head metal-on-metal hip replacements are painful: the anatomical basis of psoas impingement on the femoral head-neck junction.

Large-head metal-on-metal total hip replacement has a failure rate of almost 8% at five years, three times the revision rate of conventional hip replacement. Unexplained pain remains a feature of this type of arthroplasty. All designs of the femoral component of large-head metal-on-metal total hip replacements share a unique characteristic: a subtended angle of 120° defining the proportion of a sphere that the head represents. Using MRI, we measured the contact area of the iliopsoas tendon on the femoral head in sagittal reconstruction of 20 hips of patients with symptomatic femoroacetabular impingement. We also measured the articular extent of the femoral head on 40 normal hips and ten with cam-type deformities. Finally, we performed virtual hip resurfacing on normal and cam-type hips, avoiding overhang of the metal rim inferomedially. The articular surface of the femoral head has a subtended angle of 120° anteriorly and posteriorly, but only 100° medially. Virtual surgery in a normally shaped femoral head showed a 20° skirt of metal protruding medially where iliopsoas articulates. The excessive extent of the large-diameter femoral components may cause iliopsoas impingement independently of the acetabular component. This may be the cause of postoperative pain with these implants.

Contrasting success in the restoration of plant and phytophagous beetle assemblages of species-rich mesotrophic grasslands.

Over the last 60 years changes to the management of species-rich mesotrophic grasslands have resulted in the large-scale loss and degradation of this habitat across Europe. Restoration of such grasslands on agriculturally improved pastures provides a potentially valuable approach to the conservation of these threatened areas. Over a four-year period a replicated block design was used to test the effects of seed addition (green hay spreading and brush harvest collection) and soil disturbance on the restoration of phytophagous beetle and plant communities. Patterns of increasing restoration success, particularly where hay spreading and soil disturbance were used in combination, were identified for the phytophagous beetles. In the case of the plants, however, initial differences in restoration success in response to these same treatments were not followed by subsequent temporal changes in plant community similarity to target mesotrophic grassland. It is possible that the long-term consequences of the management treatments would not be the establishment of beetle and plant communities characteristic of the targets for restoration. Restoration management to enhance plant establishment using hay spreading and soil disturbance techniques would, however, still increase community similarity in both taxa to that of species-rich mesotrophic grasslands, and so raise their conservation value.

Computer-assisted hip resurfacing surgery using the acrobot navigation system.

The authors have previously reported on the laboratory development of the Acrobot Navigation System for accurate computer-assisted hip resurfacing surgery. This paper describes the findings of using the system in the clinical setting and including the improvements that have been made to expedite the procedure. The aim of the present system is to allow accurate planning of the procedure and precise placement of the prosthesis in accordance with the plan, with a zero intraoperative time penalty in comparison to the standard non-navigated technique. At present the navigation system is undergoing final clinical evaluation prior to a clinical study designed to demonstrate the accuracy of outcome compared with the conventional technique. While full results are not yet available, this paper describes the techniques that will be used to evaluate accuracy by comparing pre-operative computed tomography (CT)-based plans with post-operative CT scans. Example qualitative clinical results are included based on visual comparison of the plan with post-operative X-rays.

Robotic control in knee joint replacement surgery.

A brief history of robotic systems in knee arthroplasty is provided. The place of autonomous robots is then discussed and compared to more recent 'hands-on' robotic systems that can be more cost effective. The case is made for robotic systems to have a clear justification, with improved benefits compared to those from cheaper navigation systems. A number of more recent, smaller, robot systems for knee arthroplasty are also described. A specific example is given of an active constraint medical robot, the ACROBOT system, used in a prospective randomized controlled trial of unicondylar robotic knee arthroplasty in which the robot was compared to conventional surgery. The results of the trial are presented together with a discussion of the need for measures of accuracy to be introduced so that the efficacy of the robotic surgery can be immediately identified, rather than have to wait for a number of years before long-term clinical improvements can be demonstrated.

Preoperative planning and intraoperative guidance for accurate computer-assisted minimally invasive hip resurfacing surgery.

Hip resurfacing is an alternative to total hip replacement (THR) and is particularly suitable for the younger, more active patient. However, it is a more demanding procedure. This paper describes a system that enables the surgeon to plan the surgery preoperatively with optimally sized and placed components, and then transfer this plan to an intraoperative system that registers computer models to the real patient and tracks surgical tools, allowing the surgeon to ensure that the bone is resected correctly and that the components are fitted in accordance with the plan. The paper describes a series of instruments used with the system which are locked to the bone. These instruments serve the dual purpose of soft tissue retraction and bone immobilization. The system will shortly be the subject of laboratory and clinical evaluation. Registration, a cornerstone of the tracked instrument system, has been tested, and accuracy measures are provided. Experimental results for the remainder of the system will be provided after clinical trials.

Novel quorum-sensing-controlled genes in Erwinia carotovora subsp. carotovora: identification of a fungal elicitor homologue in a soft-rotting bacterium.

Seven new genes controlled by the quorum-sensing signal molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) have been identified in Erwinia carotovora subsp. carotovora. Using TnphoA as a mutagen, we enriched for mutants defective in proteins that could play a role in the interaction between E. carotovora subsp. carotovora and its plant hosts, and identified NipEcc and its counterpart in E. carotovora subsp. atroseptica. These are members of a growing family of proteins related to Nep1 from Fusarium oxysporum which can induce necrotic responses in a variety of dicotyledonous plants. NipEcc produced necrosis in tobacco, NipEca affected potato stem rot, and both affected virulence in potato tubers. In E. carotovora subsp. carotovora, nip was shown to be subject to weak repression by the LuxR family regulator, EccR, and may be regulated by the negative global regulator RsmA.

Brachytherapy--an example of a urological minimally invasive robotic procedure.

A review of the application of urological robots to the prostate is given, together with an examination of the conventional brachytherapy procedure for insertion of radioactive seeds to treat prostate cancer. The specification and design of a robotic system is provided, which can position a series of needles and radioactive pellets in accordance with a pre-operative plan. The needles can be withdrawn automatically, leaving the seeds in position.A separate motorised system is used to position a trans-rectal ultrasound (U/S) probe, which can be used to continually monitor the seed placement. The robot program can be updated intra-operatively if the U/S image shows this to be necessary. The demonstrator system has been demonstrated in-vitro using a variety of gel and animal tissue phantoms. The resulting robot performance shows this to be a viable approach.

Caesarean section conducted under subarachnoid block in two sisters with spinal muscular atrophy.

Spinal muscular atrophy is a rare chronic neurological condition characterised by degeneration of the anterior horn cell. Experience with the anaesthetic management of the pregnant patient with this condition is limited. We report the clinical details of two wheelchair-bound sisters, who underwent elective caesarean section within a few weeks of one another. Both patients were safely managed with subarachnoid anaesthesia without any deterioration of their underlying neurological condition. It is hoped that this report will add to the evidence that subarachnoid anaesthesia can safely be used for caesarean section in chronic neurological conditions and, in particular, spinal muscular atrophy.

Single room maternity care: the nursing response.

BACKGROUND: The introduction of single room maternity care in the 1990s necessitated a new approach to nursing education and practice. A focus on perinatal nursing requires competence across the spectrum of labor, delivery, postpartum and newborn care. We sought to evaluate the nursing response to this change by comparing satisfaction with the workplace environment among single room maternity care nurses before and after they worked in the setting and among nurses working in traditional birth settings. METHODS: Six months before the opening of a pilot seven-bed single room maternity care unit, nurses who planned to work in the new unit completed a survey about their satisfaction with aspects of their work environment. Three months after the new unit opened the survey was repeated with this study group and also by a sample of nurses working in the delivery and postpartum areas. RESULTS: Responses indicated that single room maternity care nurses before and after working in the unit were significantly more satisfied with the physical setting, their ability to respond to patients' needs, their opportunity for teaching families, the nursing practice environment, peer support, and their perceived level of competency. They rated their satisfaction significantly higher than that of their colleagues in the traditional delivery and postpartum settings. CONCLUSIONS: The positive transition to single room maternity care by obstetrical nurses was demonstrated by their improved overall satisfaction with the work environment. Evaluation of the nurses' responses to changes in health care delivery has important implications for justifying new clinical approaches and planning for future changes.

Therapeutic effects of cysteine protease inhibition in allergic lung inflammation: inhibition of allergen-specific T lymphocyte migration.

OBJECTIVE AND DESIGN: We have evaluated the effects of the broad-spectrum cysteine protease inhibitor E64 on allergic lung inflammation in the mouse ovalbumin model of human asthma. We have also characterised membrane-associated cathepsin enzyme activity on a range of cell types. MATERIALS: Balb/C mice, E64 and CA074, various cell lines. TREATMENT: E64 was administered by subcutaneous minipump into ovalbumin-sensitised mice prior to intranasal ovalbumin challenge. The effect of E64 on ovalbumin-induced inflammation in vivo and ovalbumin-specific T cell proliferation in vitro and ex vivo was examined. Membrane-associated cathepsin activity on various cell types was measured. RESULTS: E64 treatment (0.36-0.48 mg/day) led to a significant reduction in eosinophil numbers and lung weights in the mouse model. Histological examination of lungs confirmed the anti-inflammatory effect. E64 greatly reduced ovalbumin-specific T cell numbers in the lymph nodes draining the lung following intranasal challenge whilst an accumulation of these T cells was found in the 'priming' lymph nodes. An analysis of various cells involved in lymphocyte priming and migration revealed that monocytes, dendritic cells and endothelial cells express high levels of membrane-associated cathepsin B activity. CONCLUSIONS: Since E64 is not cell permeable and does not inhibit antigen-induced T cell proliferation in vitro or in vivo, the data indicate that membrane-associated cysteine proteases, possibly cathepsin B, may regulate T lymphocyte migration in vivo.

A correlation between versican and neurofilament expression patterns during the development and adult cycling of rat vibrissa follicles.

Versican, a proteoglycan recently implicated in hair follicle induction, has been shown to influence axon outgrowth in vitro and in vivo. We used immunohistochemistry to study the relationship between versican expression and innervation, during rat vibrissa follicle development and the adult hair cycle. During development, nerve fibres were commonly associated with areas of weak versican expression, and the path of axons appeared to be delineated by sharp boundaries of versican expression. Versican expression changed in the lower follicle dermis during the adult hair follicle cycle but remained strong around the follicle neck reflecting the constant innervation. Our observations show a correlation between versican expression and peripheral innervation indicating that versican may have a dual role in hair follicle biology.

The first clinical application of a "hands-on" robotic knee surgery system.

The performance of a novel "hands-on" robotic system for total knee replacement (TKR) surgery is evaluated. An integrated robotic system for accurately machining the bone surfaces in TKR surgery is described. Details of the system, comprising an "active constraint" robot, called Acrobot, a "gross positioning" robot, and patient clamps, are provided. The intraoperative protocol and the preoperative, CT-based, planning system are also described. A number of anatomical registration and cutting trials, using plastic bones, are described, followed by results from two preliminary clinical trials, which demonstrate the accuracy achieved in the anatomical registration. Finally, the first clinical trial is described, in which the results of the anatomical registration and bone cutting are seen to be of high quality. The Acrobot system has been successfully used to accurately register and cut the knee bones in TKR surgery. This demonstrates the great potential of a "hands-on" robot for improving accuracy and increasing safety in surgery.

Histochemical localisation of FMRFamide-gated Na+ channels in Helisoma trivolvis and Helix aspersa neurones.

FMRFamide-gated Na+ channels of molluscan neurones belong to the ENa/Deg family of channels which have diverse functions. FMRFamide (Phe-Met-Arg-Phe-NH2) Na+ channels were detected electrophysiologically in specified neurones of Helix (Helix aspersa) and Helisoma (Helisoma trivolvis), and clones (FaNaCs) subsequently identified. We have now made a study to determine the distribution of mRNA for the clones HaFaNaC (Helix) and HtFaNaC (Helisoma) in the nervous systems of these species using standard in situ hybridization techniques. Immunohistochemical experiments were also made using an HtFaNaC antibody to detect the channel protein in Helisoma neurones. Many neurones in the central ganglia, including those which exhibit the FMRFamide Na+ current, stained for FaNaC-mRNA, suggesting a much wider distribution of the channel than was indicated by the earlier work. An immunoreactive response to the channel antibody was also observed in some Helisoma neurones, such as the giant dopamine neurone of the left pedal ganglion, also shown to possess HtFaNaC-mRNA and to exhibit the FMRFamide Na+ current. Taken together, these experiments suggest that the clones HaFaNaC and HtFaNaC are major, if not the only, subunits of the FMRFamide-gated Na+ channel detected electrophysiologically in the identified neurones of these species. However, fewer neurones in Helisoma reacted with the HtFaNaC-antibody than those which exhibited message for the channel. This discrepancy may be due to a difference in sensitivity of the two techniques, or because not all of the channel mRNA is normally expressed as a membrane protein.

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination.

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged approximately 171 mg/dl and in the ETHD animals approximately 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection of ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of approximately 145,000-165,000 axons in MRC, SC and ETLD animals. About 4% of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75,000 optic nerve axons (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75,000-90,000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (approximately 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Four radiation hypersensitivity cases and their implications for clinical radiotherapy.

BACKGROUND AND PURPOSE: Over a 20 year period, four out of 2000 paediatric radiotherapy patients, treated at St. Bartholomew's Hospital (three with lymphoma, one with angiosarcoma), have revealed extreme/fatal clinical hypersensitivity in normal tissues. PATIENTS AND METHODS: Cellular hypersensitivity was confirmed in vitro and attributed to the ataxia-telangiectasia (A-T) gene in cases I and II, a newly described defect in the DNA ligase 4 gene in case III, and a novel and as yet incompletely defined, molecular defect in case IV who presented with xeroderma pigmentosum (XP). RESULTS: The severe clinical hypersensitivity preceded the cellular and molecular analysis, but did not manifest as a clinically exaggerated normal tissue reaction until 3+ weeks after the start of a conventionally fractionated course of radiotherapy, by which time the latent damage had been inflicted. There were no clinical stigmata to alert the clinician to a predisposing syndrome in two patients (cases I and II). We point out that approximately 20% of A-T patients are classified as variants with delayed expression of clinical symptoms, and case II falls into this category. CONCLUSIONS: As lymphoma (incidence, one in 100000 children) constituted the majority of the diagnoses, questions arise as to: (1), the probability of other centres having experienced and being presented in the future with similar problems (particularly bearing in mind that other oncologically predisposing radiosensitivity syndromes have not been not represented in our experience); and (2), the appropriateness, efficiency and applicability of predictive assays. Unambiguous cellular radiosensitivity would have been apparent from clonal assays on fibroblast cultures from all four cases prior to treatment, but such assays take 4-6 weeks to produce results. While estimates of chromosome damage or clonal assays on pre-treatment blood derived cells would be faster, there is a health economics issue as to the general applicability of such 'screening' assays.