Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Suppression of Emittance Growth Using a Shaped Cold Atom Electron and Ion Source.

We demonstrate precise control of charged particle bunch shape with a cold atom electron and ion source to create bunches with linear and, therefore, reversible Coulomb expansion. Using ultracold charged particles enables detailed observation of space-charge effects without loss of information from thermal diffusion, unambiguously demonstrating that shaping in three dimensions can result in a marked reduction of Coulomb-driven emittance growth. We show that the emittance growth suppression is accompanied by an increase in bunch focusability and brightness, improvements necessary for the development of sources capable of coherent single-shot ultrafast electron diffraction of noncrystalline objects, with applications ranging from femtosecond chemistry to materials science and rational drug design.

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

BACKGROUND: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF). METHODS: 422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n=111), minimal residual disease (MRD) SRT (n=70) and SRT (n=83) were defined by PSA levels of <0.2, 0.2-0.49 and ⩾0.5 ng ml(-1), respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome. RESULTS: During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P<0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P=0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. CONCLUSIONS: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.

Classification of neurological abnormalities in children with congenital melanocytic naevus syndrome identifies magnetic resonance imaging as the best predictor of clinical outcome.

BACKGROUND: The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much wider variation in outcome. OBJECTIVES: To establish whether routine MRI of the CNS is a clinically relevant investigation in children with multiple CMN (more than one at birth), and to subclassify radiological abnormalities. METHODS: Of 376 patients seen between 1991 and 2013, 289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has been more than one CMN at birth, independent of size and site of the largest naevus. Cutaneous phenotyping and radiological variables were combined in a multiple regression model of long-term outcome measures (abnormal neurodevelopment, seizures, requirement for neurosurgery). RESULTS: Twenty-one per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the most significant predictor of all outcome measures. Abnormalities were subclassified into group 1 'intraparenchymal melanosis alone' (n = 28) and group 2 'all other pathology' (n = 18). Group 1 was not associated with malignancy or death during the study period, even when symptomatic with seizures or developmental delay, whereas group 2 showed a much more complex picture, requiring individual assessment. CONCLUSIONS: For screening for congenital neurological lesions a single MRI in multiple CMN is a clinically relevant strategy. Any child with a stepwise change in neurological/developmental symptoms or signs should have an MRI with contrast of the brain and spine to look for new CNS melanoma.

Right-sided congestive heart failure in a dog because of a primary intracavitary myocardial lymphoma.

CASE REPORT: A 9-year-old female intact Cocker Spaniel was presented with a history of acute-onset dyspnoea and abdominal distension of 3 days' duration. Ultrasonography revealed pleural, peritoneal and pericardial effusions. Abdominal fluid analysis was consistent with a modified transudate. Echocardiography revealed a large, hypoechoic space-occupying mass within the right atrium. The dog was euthanased and the postmortem examination showed a solid, 40 × 35 × 20 mm broad-based mass arising from the right atrial wall and occluding approximately 90% of the right atrial lumen. Histopathology revealed myocardial lymphoma. There were histologically similar, focal nodules in the lung parenchyma without involvement of other extracardiac sites. There was gross and histological evidence of hepatic congestion and marked distension of the caudal vena cava, consistent with secondary right-sided congestive heart failure. CONCLUSION: This case highlights the need to consider lymphoma as a differential diagnosis for an intra-atrial mass and as a cause of congestive heart failure in the dog.

A genomic classifier predicting metastatic disease progression in men with biochemical recurrence after prostatectomy.

BACKGROUND: Due to their varied outcomes, men with biochemical recurrence (BCR) following radical prostatectomy (RP) present a management dilemma. Here, we evaluate Decipher, a genomic classifier (GC), for its ability to predict metastasis following BCR. METHODS: The study population included 85 clinically high-risk patients who developed BCR after RP. Time-dependent receiver operating characteristic (ROC) curves, weighted Cox proportional hazard models and decision curves were used to compare GC scores to Gleason score (GS), PSA doubling time (PSAdT), time to BCR (ttBCR), the Stephenson nomogram and CAPRA-S for predicting metastatic disease progression. All tests were two-sided with a type I error probability of 5%. RESULTS: GC scores stratified men with BCR into those who would or would not develop metastasis (8% of patients with low versus 40% with high scores developed metastasis, P<0.001). The area under the curve for predicting metastasis after BCR was 0.82 (95% CI, 0.76-0.86) for GC, compared to GS 0.64 (0.58-0.70), PSAdT 0.69 (0.61-0.77) and ttBCR 0.52 (0.46-0.59). Decision curve analysis showed that GC scores had a higher overall net benefit compared to models based solely on clinicopathologic features. In multivariable modeling with clinicopathologic variables, GC score was the only significant predictor of metastasis (P=0.003). CONCLUSIONS: When compared to clinicopathologic variables, GC better predicted metastatic progression among this cohort of men with BCR following RP. While confirmatory studies are needed, these results suggest that use of GC may allow for better selection of men requiring earlier initiation of treatment at the time of BCR.

Primary bone tumors in birds: a review and description of two new cases.

Primary bone tumors are only occasionally reported in avian species. This paper presents the cases of an osteosarcoma in a 6-yr-old free-range chicken and a chondrosarcoma in a 3-yr-old barred Plymouth Rock chicken. The well-differentiated, moderately productive osteoblastic osteosarcoma arose from the synsacral vertebrae and had metastasized to the liver. The chondrosarcoma was well differentiated and firmly attached to the left side of the keel. There was no evidence of metastasis.

Bone volume and regional density of the central tarsal bone detected using computed tomography in a cross-sectional study of adult racing greyhounds.

AIMS: To determine whether left-to-right asymmetry of the central tarsal bone (CTB) of racing greyhounds was detectable using computed tomography (CT) in live dogs; to quantify the asymmetry in terms of average bone volume, volumetric bone mineral density (vBMD), and dorsal cortical shape, and to determine if age, gender, bodyweight, number of starts or history of tarsal injury were significant covariates. METHODS: One trainer supplied 11 male and seven female, unrelated, skeletally mature, actively racing greyhounds, including dogs with a history of tarsal injury diagnosed by the trainer and/or track veterinarian (n=8), and dogs without a history of tarsal injury (n=10). Using CT, standardised parameters of the CTB were measured including volume and average vBMD of the left and right CTB, vBMD of regions within the CTB, and bone shape. RESULTS: There was no difference in the volumes of the left and right CTB and no association with number of racing starts. Volume of CTB in dogs with a history of tarsal injury was greater than in dogs with no history of injury (p<0.001). Mean vBMD of the right was greater than the left CTB (p=0.004), and was independent of history of injury, gender, bodyweight, and number of starts. Males with a history of injury weighed more than those with no history of injury (p=0.004). The region of greatest difference in vBMD between right and left limbs was the centrodorsomedial aspect of the CTB. Middle plantar ligament enthesiopathies and fractures of tarsal bones other than the central tarsal bone were identified in dogs with and without a history of tarsal injury. CONCLUSIONS: Significant left-to-right asymmetry of the CTB in racing greyhounds was detected using CT. Contrary to previous suggestions, the asymmetry was not associated with the number of racing starts. We propose that the majority of the adaptive modelling of the CTB occurred rapidly following the onset of counter-clockwise training, with little further modelling throughout the racing career of the dog, however further investigation is warranted. CLINICAL RELEVANCE: This study described a technique using CT for imaging the CTB in live dogs, which opens the way for a longitudinal study of bone modelling of the CTB in response to training and racing in a counter-clockwise direction.

Mucopolysaccharidosis type VI in a Miniature Poodle-type dog caused by a deletion in the arylsulphatase B gene.

AIM: To investigate and characterise an inborn error of metabolism in a dog with skeletal and ocular abnormalities. METHODS: A 2.5-year-old small male Miniature Poodle-like dog was presented with gross joint laxity and bilateral corneal opacities. Clinical examination was augmented by routine haematology, serum chemistry, radiographs, pathology, enzymology and molecular genetic studies. Euthanasia was requested when the dog was 3 years of age because of progressively decreasing quality of life. RESULTS: Radiology revealed generalised epiphyseal dysplasia, malformed vertebral bodies, luxation/subluxation of appendicular and lumbosacral joints with hypoplasia of the odontoid process and hyoid apparatus. These clinical and radiographic findings, together with a positive urinary Berry spot test for mucopolysaccharides, and metachromatic granules in leucocytes, were indicative of a mucopolysaccharidosis (MPS), a lysosomal storage disease. Histological lesions included vacuolation of stromal cells of the cornea, fibroblasts, chondrocytes, macrophages and renal cells. The brain was essentially normal except for moderate secondary Wallerian-type degeneration in motor and sensory tracts of the hind brain. Dermatan sulphate-uria was present and enzymology revealed negligible activity of N-acetylgalactosamine-4-sulphatase, also known as arylsulphatase B, in cultured fibroblasts and liver tissue. A novel homozygous 22 base pair (bp) deletion in exon 1 of this enzyme's gene was identified (c.103_124del), which caused aframe-shift and subsequent premature stop codon. The "Wisdom pure breed-mixed breed" test reported the dog as a cross between a Miniature and Toy Poodle. CONCLUSIONS: The clinicopathological features are similar to those of MPS type VI as previously described in dogs, cats and other species, and this clinical diagnosis was confirmed by enzymology and molecular genetic studies. This is an autosomal recessively inherited lysosomal storage disease. CLINICAL RELEVANCE: The prevalence of MPS VI in Miniature or Toy Poodles in New Zealand and elsewhere is currently unknown. Due to the congenital nature of the disorder, malformed pups may be subject to euthanasia without investigation and the potential genetic problem in the breed may not be fully recognised. The establishment of a molecular genetic test now permits screening for this mutation as a basis to an informed breeding policy.

Developmental plasticity as a cohesive evolutionary process between sympatric alternate-year insect cohorts.

Many species, particularly insects, pass through a series of distinct phases during their life history, with the developmental timing directed towards appropriate resources. Any factor that creates variation in developmental timing may partition a population into discrete populations-or 'cohorts'. Where there is continued failure to recruit outside the natal cohort then alternate cohorts will have their own internal dynamics, eventually leading to independent demographic and evolutionary trajectories. By contrast, continued variation in development rates within a cohort-cohort splitting-may homogenise otherwise independent demographic units. Using a panel of 14 microsatellite loci, we quantify the genetic signature of apparent demographic isolation between coexisting, but alternate, semivoltine cohorts of the damselfly Coenagrion mercuriale at locations that span its distribution in the UK. We find consistently low levels of genetic divergence between sympatric cohorts of C. mercuriale, indicative of developmental plasticity during the larval stage (unregulated development) whereby some individuals complete their development outside the predominant 2-year (semivoltine) period. Thus, individuals that alter their developmental rate successfully recruit to a different cohort. Despite maintaining contrasting population sizes, gene flow between alternate cohorts broadly is sufficient to place them on a similar evolutionary trajectory and also buffers against loss of genetic diversity. Such flexible larval development permits a response to local conditions and may facilitate response to environmental change.

Haemangiosarcoma of the interventricular septum in a dog.

UNLABELLED: Abstract CASE HISTORY: A 5-year-old male neutered Labrador Retriever Afghan crossbred dog was examined after collapsing. The dog was recumbent, dyspnoeic and mildly tachypnoeic. There was a tachyarrhythmia (300 beats per minute) and subcutaneous oedema of the ventral neck and right forelimb. CLINICAL FINDINGS: The dog had a sustained ventricular tachycardia originating in the right ventricle and on echocardiography a mass was identified in the interventricular septum. Due to the poor prognosis the owners agreed to euthanasia of the dog. PATHOLOGICAL FINDINGS: A reddish-grey mass was found in the interventricular septum and smaller red foci found scattered throughout the myocardium. There was a single, raised, splenic nodule with several smaller red foci within the splenic parenchyma. Hepatic congestion, pancreatic oedema, ascites and subcutaneous oedema of the right forelimb and neck were present. Sections of the splenic nodule, interventricular septal mass and both ventricular-free walls showed neoplastic mesenchymal cells. DIAGNOSIS: Haemangiosarcoma of the myocardium and spleen with right-sided congestive heart failure. CLINICAL RELEVANCE: This case report describes an atypical location for haemangiosarcoma. The investigation supports the use of echocardiography as a component of the protocol for staging haemangiosarcoma even in the absence of apericardial effusion. It also provides further evidence for the inclusion of intracardiac neoplasia as a differential diagnosis for dogs with unexplained cardiac arrhythmias.

Probable avulsion of the infraspinatus tendon of insertion in a Rottweiler.

CASE HISTORY: An 8.5-month-old male Rottweiler was presented with chronic, non-localisable, right forelimb lameness. CLINICAL FINDINGS: Survey radiographs revealed panosteitis in the right antebrachium and an irregularly marginated radiolucency on the lateral aspect of the proximal left humerus. The tendon of insertion of the left infraspinatus muscle was enlarged, some tendon fibres ended prematurely in a cluster of mineralised particles, and there was a large bony defect at the point of insertion. DIAGNOSIS: Probable avulsion of the left infraspinatus tendon. CLINICAL RELEVANCE: This case was particularly unusual due to the marked prominence of the lesion without lameness of the left forelimb. Avulsion of the infraspinatus tendon is poorly described in the veterinary and medical literature.

Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours.

BACKGROUND: Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T. METHODS: From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity. RESULTS: In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype. CONCLUSION: Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age.

Idiopathic canine juvenile cranial hyperostosis in a Pit Bull Terrier.

CASE HISTORY: An 8-month-old male Pit Bull Terrier was presented with bilateral firm swellings of the cranium in the region of the frontal sinuses. The dog was aggressive when approached and had also been anorexic during the 3.5 days prior to presentation. CLINICAL FINDINGS: Using computed tomography (CT) and radiology, periosteal new bone formation and hyperostosis were detected on the frontal, parietal and mandibular bones bilaterally. Histopathology of the calvarial and mandibular bones was similar, comprised of thick trabeculae of immature woven and mature lamellar bone separated by cementing lines. Sites of prominent osteoblastic and osteoclastic activity were also present. DIAGNOSIS: Craniomandibular osteopathy with clinical similarities to calvarial hyperostosis. CLINICAL RELEVANCE: Pit Bull Terriers are not predisposed to either craniomandibular osteopathy or calvarial hyperostosis. This observation, in addition to the clinical and pathological similarities between the two diseases, suggests that craniomandibular osteopathy and calvarial hyperostosis may represent a single disorder, with predilection sites that vary between breeds of dog. We propose a new term, idiopathic canine juvenile cranial hyperostosis, for this disorder, to include both craniomandibular osteopathy and calvarial hyperostosis.

A comparative analysis of senescence in adult damselflies and dragonflies (Odonata).

Any population whose members are subject to extrinsic mortality should exhibit an increase in mortality with age. Nevertheless, the prevailing opinion is that populations of adult damselflies and dragonflies do not exhibit such senescence. Here, we challenge this contention by fitting a range of demographic models to the data on which these earlier conclusions were based. We show that a model with an exponential increase in age-related mortality (Gompertz) generally provides a more parsimonious fit than alternative models including age-independent mortality, indicating that many odonates do indeed senesce. Controlling for phylogeny, a comparison of the daily mortality of 35 odonate species indicates that although male and female mortalities are positively correlated, mortality tends to be higher in males of those species that exhibit territoriality. Hence, we show for the first time that territoriality may impose a survivorship cost on males, once the underlying phylogenetic relationships are accounted for.

Empirical evidence of senescence in adult damselflies (Odonata: Zygoptera).

1. Age-dependent increases in mortality have been documented in a variety of species of insect under laboratory conditions. However, while strong statistical evidence has been presented for senescence in vertebrate populations in the wild, we know little about the rate and shape of senescence in wild populations of insects. 2. Odonates (damselflies and dragonflies) provide excellent candidate species for evaluating demographic senescence as they are large enough to be marked individually and they are easily re-sighted without recapture. The prevailing opinion - based entirely on qualitative examination of the declines in log numbers alive with time since marking - is that odonates exhibit age-independent daily survivorship. 3. Here, we examine mark-recapture data on the Azure Damselfly Coenagrion puella over two consecutive seasons. For the first time, we evaluate and compare the fit of quantitative models that not only account for weather-dependent daily variation in daily re-sighting rates, but also age-dependent variation in daily survivorship. 4. Models with age-dependent declines in daily survivorship provide a more parsimonious explanation for the data than similar models without these age-dependent effects. In general, models in which mortality increases in an exponential (Gompertz) fashion explain the mark-recapture sequences more efficiently than a range of alternative models, including those in which mortality increases as a power function (Weibull) or reaches a plateau (logistic). These results are indicative of a general senescent decline in physiological functioning, which is particularly marked after 15 days as a mature adult. 5. Weather (temperature, sun and precipitation) and initial mite load influenced the probability of daily re-sighting. Weather and mite load also influenced daily survivorship, but their effects differed between seasons. 6. Overall, fitting models with age as an explicit covariate demonstrates that odonates do indeed senesce. This contradicts previously held assumptions that Odonata do not exhibit age-dependent survivorship in the wild.

Degenerative lumbosacral stenosis in working dogs: current concepts and review.

Degenerative lumbosacral stenosis (DLSS) is characterised by intervertebral disc degeneration, with secondary bony and soft-tissue changes leading to compression of the cauda equina. Large-breed, active and working dogs are the most commonly affected by DLSS. Specific manipulative tests allow the clinician to form a high suspicion of DLSS, and initiate investigation. Changes seen using conventional radiography are unreliable, and although contrast radiography represents an improvement, advanced imaging is accepted as the diagnostic method of choice. Treatment involves decompression and/or stabilisation procedures in working dogs, although conservative management may be acceptable in pet dogs with mild signs. Prognosis for return to work is only fair, and there is a high rate of recurrence following conventional surgery. Stabilisation procedures are associated with the potential for failure of the implant, and their use has not gained universal acceptance. A new surgical procedure, dorsolateral foramenotomy, offers a potential advance in the management of DLSS. everal aspects of the pathogenesis, heritability and optimal treatment approach remain uncertain.

Molecular and ecological evidence for small-scale isolation by distance in an endangered damselfly, Coenagrion mercuriale.

Coenagrion mercuriale (Charpentier) (Odonata: Zygoptera) is one of Europe's most threatened damselflies and is listed in the European Habitats directive. We combined an intensive mark-release-recapture (MRR) study with a microsatellite-based genetic analysis for C. mercuriale from the Itchen Valley, UK, as part of an effort to understand the dispersal characteristics of this protected species. MRR data indicate that adult damselflies are highly sedentary, with only a low frequency of interpatch movement that is predominantly to neighbouring sites. This restricted dispersal leads to significant genetic differentiation throughout most of the Itchen Valley, except between areas of continuous habitat, and isolation by distance (IBD), even though the core populations are separated by less than 10 km. An urban area separating some sites had a strong effect on the spatial genetic structure. Average pairwise relatedness between individual damselflies is positive at short distances, reflecting fine-scale genetic clustering and IBD both within- and between-habitat patches. Damselflies from a fragmented habitat have higher average kinship than those from a large continuous population, probably because of poorer dispersal and localized breeding in the former. Although indirect estimates of gene flow must be interpreted with caution, it is encouraging that our results indicate that the spatial pattern of genetic variation matches closely with that expected from direct observations of movement. These data are further discussed with respect to possible barriers to dispersal within the study site and the ecology and conservation of C. mercuriale. To our knowledge, this is the first report of fine-scale genetic structuring in any zygopteran species.

Investigation into the validity of two-dimensional models for sound radiation from waves in rails.

The sound radiation from a vibrating rail can be predicted using a two-dimensional model under certain conditions. This paper explores these conditions and shows that, if the decay rate of vibration along the rail becomes large or the wavelength in the rail becomes small, it becomes necessary to allow for three-dimensional radiation characteristics. In practice, however, noise from a rail can be predicted using a two-dimensional model for frequencies above about 250 Hz, and even where three-dimensional effects become important, these can be allowed for by simple correction terms. When the wavelength in the rail approaches that of acoustic waves in air, the angle between the direction of sound radiation from the rail and the normal to the rail increases, in some cases to more than 45 degrees. This must be accounted for if the performance of noise barriers is to be calculated using a two-dimensional approach.