Endemic species may have complex histories: within-refugium phylogeography of an endangered Iberian vole.

Glacial refugia protected and promoted biodiversity during the Pleistocene, not only at a broader scale, but also for many endemics that contracted and expanded their ranges within refugial areas. Understanding the evolutionary history of refugial endemics is especially important in the case of endangered species to recognize the origins of their genetic structure and thus produce better informed conservation practices. The Iberian Peninsula is an important European glacial refugium, rich in endemics of conservation concern, including small mammals, such as the Cabrera vole (Microtus cabrerae). This near-threatened rodent is characterized by an unusual suite of genetic, life history and ecological traits, being restricted to isolated geographic nuclei in fast-disappearing Mediterranean subhumid herbaceous habitats. To reconstruct the evolutionary history of the Cabrera vole, we studied sequence variation at mitochondrial, autosomal and sex-linked loci, using invasive and noninvasive samples. Despite low overall mitochondrial and nuclear nucleotide diversities, we observed two main well-supported mitochondrial lineages, west and east. Phylogeographic modelling in the context of the Cabrera vole's detailed fossil record supports a demographic scenario of isolation of two populations during the Last Glacial Maximum from a single focus in the southern part of the Iberian Peninsula. In addition, our data suggest subsequent divergence within the east, and secondary contact and introgression of the expanding western population, during the late Holocene. This work emphasizes that refugial endemics may have a phylogeographic history as rich as that of more widespread species, and conservation of such endemics includes the preservation of that genetic legacy.

[Exploring Patient Motives to Use Emergency Departments for Non-urgent Conditions: A Qualitative Study]. / Inanspruchnahme zentraler Notaufnahmen: Qualitative Erhebung der Motivation von Patientinnen und Patienten mit nichtdringlichem Behandlungsbedarf.

Background: The increasing utilization of Emergency Departments (ED) by outpatients with acute but non-urgent conditions contributes to ED crowding. This study aims to explore the motives of patients categorized as non-urgent for visiting the ED. Methods: A qualitative study based on semi-structured interviews was conducted at 2 ED's at Charité Berlin. A total of 40 patients categorized as non-urgent were interviewed. Data were analyzed using Qualitative Content Analysis. Results: In addition to unavailable appointments or having to wait a long time for an appointment with general practitioners and specialists, patients stated better time-flexibility, the University Hospital's quality of care and the availability of multidisciplinary care as reasons to seek medical care in the ED. Because of the 24/7 availability of EDs, some patients seem to make little effort to seek an appointment with a GP or a specialist outside the hospital. Conclusion: Our interview data indicate an independent function of EDs in outpatient care. It must be assumed that even a full coverage of service guarantee by the association of statuary health insurance physicians would not reduce ED utilization to cases of medical urgency only. To ensure sustainable medical quality for urgent as well as non-urgent medical care seekers, EDs need appropriate resources to cover the demand.

A voyage to Terra Australis: human-mediated dispersal of cats.

BACKGROUND: Cats have been transported as human commensals worldwide giving rise to many feral populations. In Australia, feral cats have caused decline and extinction of native mammals, but their time of introduction and origin is unclear. Here, we investigate hypotheses of cat arrival pre- or post-European settlement, and the potential for admixture between cats of different invasion events. We analyse the genetic structure and diversity of feral cats from six locations on mainland Australia, seven Australian islands and samples from Southeast Asia and Europe using microsatellite and mitochondrial DNA data. RESULTS: Our results based on phylogeographic model selection are consistent with a European origin of cats in Australia. We find genetic distinctiveness of Australian mainland samples compared with Dirk Hartog Island, Flinders Island, Tasman Island and Cocos (Keeling) Island samples, and genetic similarities between some of the island populations. Historical records suggest that introduction of cats to these islands occurred at the time of European exploration and/or in connection with the pearling, whaling and sealing trades early in the 19th century. On-going influx of domestic cats into the feral cat population is apparently causing the Australian mainland populations to be genetically differentiated from those island populations, which likely are remnants of the historically introduced cat genotypes. CONCLUSION: A mainly European origin of feral cats in Australia, with possible secondary introductions from Asia following the initial establishment of cats in Australia is reasonable. The islands surrounding Australia may represent founding populations and are of particular interest. The results of the study provide an important timeframe for the impact of feral cats on native species in Australia.

The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

BACKGROUND: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. METHOD: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. RESULTS: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. CONCLUSIONS: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

BACKGROUND: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. METHODS: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. FINDINGS: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). INTERPRETATION: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

Of mice and the 'Age of Discovery': the complex history of colonization of the Azorean archipelago by the house mouse (Mus musculus) as revealed by mitochondrial DNA variation.

Humans have introduced many species onto remote oceanic islands. The house mouse (Mus musculus) is a human commensal and has consequently been transported to oceanic islands around the globe as an accidental stowaway. The history of these introductions can tell us not only about the mice themselves but also about the people that transported them. Following a phylogeographic approach, we used mitochondrial D-loop sequence variation (within an 849- to 864-bp fragment) to study house mouse colonization of the Azores. A total of 239 sequences were obtained from all nine islands, and interpretation was helped by previously published Iberian sequences and 66 newly generated Spanish sequences. A Bayesian analysis revealed presence in the Azores of most of the D-loop clades previously described in the domesticus subspecies of the house mouse, suggesting a complex colonization history of the archipelago as a whole from multiple geographical origins, but much less heterogeneity (often single colonization?) within islands. The expected historical link with mainland Portugal was reflected in the pattern of D-loop variation of some of the islands but not all. A more unexpected association with a distant North European source area was also detected in three islands, possibly reflecting human contact with the Azores prior to the 15th century discovery by Portuguese mariners. Widening the scope to colonization of the Macaronesian islands as a whole, human linkages between the Azores, Madeira, the Canaries, Portugal and Spain were revealed through the sharing of mouse sequences between these areas. From these and other data, we suggest mouse studies may help resolve historical uncertainties relating to the 'Age of Discovery'.

Building a sustainable clinical academic workforce to meet the future healthcare needs of Australia and New Zealand: report from the first summit meeting.

The delivery of healthcare that meets the requirements for quality, safety and cost-effectiveness relies on a well-trained medical workforce, including clinical academics whose career includes a specific commitment to research, education and/or leadership. In 2011, the Medical Deans of Australia and New Zealand published a review on the clinical academic workforce and recommended the development of an integrated training pathway for clinical academics. A bi-national Summit on Clinical Academic Training was recently convened to bring together all relevant stakeholders to determine how best to do this. An important part understood the lessons learnt from the UK experience after 10 years since the introduction of an integrated training pathway. The outcome of the summit was to endorse strongly the recommendations of the medical deans. A steering committee has been established to identify further stakeholders, solicit more information from stakeholder organisations, convene a follow-up summit meeting in late 2015, recruit pilot host institutions and engage the government and future funders.

Relationship between wild greylag and European domestic geese based on mitochondrial DNA.

The origins of the European domestic goose are uncertain. The available information comes from archaeological findings and historical literature, but genetic evidence has hitherto been scarce. The domestic goose in Europe is derived from the greylag goose (Anser anser), but it is not known where the initial domestication took place and which of the two subspecies of greylag goose was ancestral. We aimed to determine the amount and geographical distribution of genetic diversity in modern populations of greylag geese as well as in different breeds of the domestic goose to make inferences about goose domestication. We studied DNA sequence variation in the mitochondrial control region of greylag geese from multiple populations across Europe and western Asia as well as specimens of domestic geese representing 18 modern breeds and individuals not belonging to any recognised breed. Our results show notable differences in genetic diversity between different greylag goose populations and the presence of six mitochondrial haplogroups which show a degree of geographical partitioning. The genetic diversity of the domestic goose is low, with 84% of sampled individuals having one of two major closely related haplotypes, suggesting that modern European domestic geese may derive from a narrow genetic base. The site of domestication remains unresolved, but domestic geese in Turkey were unusually diverse, indicating the importance of further sampling in the vicinity of the eastern Mediterranean and the Near East. There appears to be past or ongoing hybridisation between greylags and domestic geese in particular areas, consistent with field observations.

Relaxed functional constraints on triplicate α-globin gene in the bank vole suggest a different evolutionary history from other rodents.

Gene duplication plays an important role in the origin of evolutionary novelties, but the mechanisms responsible for the retention and functional divergence of the duplicated copy are not fully understood. The α-globin genes provide an example of a gene family with different numbers of gene duplicates among rodents. Whereas Rattus and Peromyscus each have three adult α-globin genes (HBA-T1, HBA-T2 and HBA-T3), Mus has only two copies. High rates of amino acid evolution in the independently derived HBA-T3 genes of Peromyscus and Rattus have been attributed to positive selection. Using RACE PCR, reverse transcription-PCR (RT-PCR) and RNA-seq, we show that another rodent, the bank vole Clethrionomys glareolus, possesses three transcriptionally active α-globin genes. The bank vole HBA-T3 gene is distinguished from each HBA-T1 and HBA-T2 by 20 amino acids and is transcribed 23- and 4-fold lower than HBA-T1 and HBA-T2, respectively. Polypeptides corresponding to all three genes are detected by electrophoresis, demonstrating that the translated products of HBA-T3 are present in adult erythrocytes. Patterns of codon substitution and the presence of low-frequency null alleles suggest a postduplication relaxation of purifying selection on bank vole HBA-T3.

Origin of the chromosomal radiation of Madeiran house mice: a microsatellite analysis of metacentric chromosomes.

Chromosome races of Mus musculus domesticus are characterised by particular sets of metacentric chromosomes formed by Robertsonian fusions and whole-arm reciprocal translocations. The Atlantic island of Madeira is inhabited by six chromosome races of house mice with 6-9 pairs of metacentric chromosomes. Three of these races are characterised by the metacentric 3.8 also found elsewhere in the distribution of M. m. domesticus, including Denmark and Spain. We investigated the possibility that metacentric 3.8 was introduced to Madeira during the initial colonisation, as this could have 'seeded' the cascade of chromosomal mutation that is the basis of the extraordinary chromosomal radiation observed on the island. Variation at 24 microsatellite loci mapping to three different chromosomal regions (proximal, interstitial and distal) of mouse chromosomes 3 and 8 was investigated in 179 mice from Madeira, Denmark, Portugal, Spain, Italy and Scotland. Analyses of microsatellite loci closely linked to the centromeres of these chromosomes ('proximal loci') do not support a common evolutionary origin of metacentric 3.8 among Madeiran, Danish and Spanish mouse populations. Our results suggest that Madeiran mice are genetically more similar to standard karyotype mice from Portugal than to metacentric mice from elsewhere. There is expected to be an interruption to gene flow between hybridising metacentric races on Madeira, particularly in the chromosomal regions close to the rearrangement breakpoints. Consistent with this, relating to differentiation involving chromosomes 3 and 8 on Madeira, we found greater genetic structure among races for proximal than interstitial or distal loci.

Combined positron emission tomography and contrast enhanced CT (PET/CeCT) is a feasible single investigation in the staging of oesophagogastric cancers: single-centre pilot study experience during the COVID-19 pandemic.

INTRODUCTION: Staging of oesophagogastric (OG) cancers usually involves endoscopy (OGD), and separate visits for contrast enhanced computed tomography (CeCT) and positron emission tomography (PET/CT). At the height of the COVID-19 pandemic, some of our patients underwent single-visit combined staging with PET/CeCT. We compare this novel pathway with standard separate imaging in time to completion of staging, to start of treatment, and cost. METHODS: We identified all patients discussed at our OG multidisciplinary team (MDT) meeting in 2020. Clinical records revealed dates of investigations and treatments. Data were tabulated in Excel, with statistical analysis in SPSS. All patients followed the same MDT process and image reviewing criteria. Costs were compared using prices supplied by finance departments. RESULTS: A total of 211 new patients were discussed at our MDT in 2020. Of these, 48 patients had combined PET/CeCT staging, and 68 had separate scans. Median time (interquartile range) in days from OGD to final imaging was 9 (6-23) for the combined group versus 21 (16-28) for the separate group (p≤0.001). Median time (days) from OGD to treatment start was 37 (29-52) for combined versus 55 (40-71) for separate (p≤0.001). No combined scans were of insufficient diagnostic quality for the MDT. PET/CeCT had a potential cost saving of £113 per patient. CONCLUSIONS: PET/CeCT allows accurate radiological staging of OG cancers with a single scan. Patients completed staging and started treatment faster, with a potential saving of £10,509 in one year. PET/CeCT has become standard staging at our trust, and we aim to incorporate radiotherapy planning images too.

Fellow travellers: a concordance of colonization patterns between mice and men in the North Atlantic region.

BACKGROUND: House mice (Mus musculus) are commensals of humans and therefore their phylogeography can reflect human colonization and settlement patterns. Previous studies have linked the distribution of house mouse mitochondrial (mt) DNA clades to areas formerly occupied by the Norwegian Vikings in Norway and the British Isles. Norwegian Viking activity also extended further westwards in the North Atlantic with the settlement of Iceland, short-lived colonies in Greenland and a fleeting colony in Newfoundland in 1000 AD. Here we investigate whether house mouse mtDNA sequences reflect human history in these other regions as well. RESULTS: House mice samples from Iceland, whether from archaeological Viking Age material or from modern-day specimens, had an identical mtDNA haplotype to the clade previously linked with Norwegian Vikings. From mtDNA and microsatellite data, the modern-day Icelandic mice also share the low genetic diversity shown by their human hosts on Iceland. Viking Age mice from Greenland had an mtDNA haplotype deriving from the Icelandic haplotype, but the modern-day Greenlandic mice belong to an entirely different mtDNA clade. We found no genetic association between modern Newfoundland mice and the Icelandic/ancient Greenlandic mice (no ancient Newfoundland mice were available). The modern day Icelandic and Newfoundland mice belong to the subspecies M. m. domesticus, the Greenlandic mice to M. m. musculus. CONCLUSIONS: In the North Atlantic region, human settlement history over a thousand years is reflected remarkably by the mtDNA phylogeny of house mice. In Iceland, the mtDNA data show the arrival and continuity of the house mouse population to the present day, while in Greenland the data suggest the arrival, subsequent extinction and recolonization of house mice--in both places mirroring the history of the European human host populations. If house mice arrived in Newfoundland with the Viking settlers at all, then, like the humans, their presence was also fleeting and left no genetic trace. The continuity of mtDNA haplotype in Iceland over 1000 years illustrates that mtDNA can retain the signature of the ancestral house mouse founders. We also show that, in terms of genetic variability, house mouse populations may also track their host human populations.

Cryptic speciation in the field vole: a multilocus approach confirms three highly divergent lineages in Eurasia.

Species are generally described from morphological features, but there is growing recognition of sister forms that show substantial genetic differentiation without obvious morphological variation and may therefore be considered 'cryptic species'. Here, we investigate the field vole (Microtus agrestis), a Eurasian mammal with little apparent morphological differentiation but which, on the basis of previous sex-linked nuclear and mitochondrial DNA (mtDNA) analyses, is subdivided into a Northern and a Southern lineage, sufficiently divergent that they may represent two cryptic species. These earlier studies also provided limited evidence for two major mtDNA lineages within Iberia. In our present study, we extend these findings through a multilocus approach. We sampled 163 individuals from 46 localities, mainly in Iberia, and sequenced seven loci, maternally, paternally and biparentally inherited. Our results show that the mtDNA lineage identified in Portugal is indeed a distinct third lineage on the basis of other markers as well. In fact, multilocus coalescent-based methods clearly support three separate evolutionary units that may represent cryptic species: Northern, Southern and Portuguese. Divergence among these units was inferred to have occurred during the last glacial period; the Portuguese lineage split occurred first (estimated at c. 70 000 bp), and the Northern and Southern lineages separated at around the last glacial maximum (estimated at c. 18 500 bp). Such recent formation of evolutionary units that might be considered species has repercussions in terms of understanding evolutionary processes and the diversity of small mammals in a European context.

Properties of a hybrid zone between highly distinct chromosomal races of the house mouse (Mus musculus domesticus) in Northern Italy, and comparisons with other hybrid zones.

Here we provide the first detailed description of the hybrid zone between the Cremona chromosomal race of house mouse (ICRE; 2n = 22) and the standard all-telocentric race (40ST; 2n = 40), with full karyotypes of 106 individuals from 17 localities along a transect between the 2 races to the west of Lake Garda in Northern Italy. The ICRE race is characterised by 9 pairs of metacentric chromosomes in a homozygous state and we use the metacentric frequency data along the transect to fit tanh metacentric clines. The clines are narrow (5-8 km, standardised width) suggesting low hybrid fitness. However, the lack of occurrence of ICRE × 40ST F(1) hybrids and presence of other hybrid types suggests that the F(1) hybrids initially produced in this hybrid zone were at least partially fertile, despite having 9 meiotic trivalent configurations. We apply the same cline-fitting methodology to 3 previously studied hybrid zones between metacentric races and the 40ST race. Taken together with published clinal data on 4 further metacentric-40ST hybrid zones, we are able to make objective generalisations on the characteristics of such zones in the house mouse. Zones involving 22-chromosome races are narrower, on average, than other metacentric-40ST hybrid zones and do not show a tendency towards the generation of new races as found with zones where the metacentric race has a higher 2n. It appears that metacentric-40ST zones are unlikely to be sites of speciation (even when a 22-chromosome race is involved), although a mosaic structure to the hybrid zone may enhance this possibility. We make a comparison between metacentric-40ST zones and contacts between 2 metacentric races, for a comprehensive perspective of chromosomal hybrid zones in the house mouse.

Natural hybridization between extremely divergent chromosomal races of the common shrew (Sorex araneus, Soricidae, Soricomorpha): hybrid zone in Siberia.

Chromosomal races of the common shrew differ in sets of metacentric chromosomes and on contact may produce hybrids with extraordinarily complex configurations at meiosis I that are associated with reduced fertility. There is an expectation that these may be some of the most extreme tension zones available for study and therefore are of interest as potential sites for reproductive isolation. Here, we analyse one of these zones, between the Novosibirsk race (characterized by metacentrics go, hn, ik, jl, mp and qr) and the Tomsk race (metacentrics gk, hi, jl and mn and acrocentrics o, p, q and r), which form hybrids with a chain-of-nine (CIX) and a chain-of-three (CIII) configuration at meiosis I. At the Novosibirsk-Tomsk hybrid zone, the CIX chromosomes form clines of 8.53 km standardized width on average, whereas the cline for the CIII chromosomes was 52.83 km wide. The difference in these cline widths fits with the difference in meiotic errors expected with the CIX and CIII configuration, and we produce estimates of selection against hybrids with these types of configurations, which we relate to dispersal and age of the hybrid zone. The hybrid zone is located at the isocline at 200 m altitude above sea level; this relationship between the races and altitude is suggested at both coarse and fine scales. This indicates adaptive differences between the races that may in turn have been promoted by the chromosome differences. Thus, the extreme chromosomal divergence between the Novosibirsk and Tomsk may be associated with genic differentiation, but it is still striking that, despite the large chromosomal differences, reproductive isolation between the Novosibirsk and Tomsk races has not occurred.

Natural hybridization between extremely divergent chromosomal races of the common shrew (Sorex araneus, Soricidae, Soricomorpha): hybrid zone in European Russia.

The Moscow and Seliger chromosomal races of the common shrew differ by Robertsonian fusions and possibly whole-arm reciprocal translocations (WARTs) such that their F1 hybrids produce a chain-of-eleven configuration at meiosis I and are expected to suffer substantial infertility. Of numerous hybrid zones that have been described in the common shrew, those between the Moscow and Seliger races involve the greatest chromosomal difference. We collected 211 individuals from this zone to generate a total dataset of 298 individuals from 187 unique global positioning system (GPS) locations within the vicinity of interracial contact. We used a geographic information system (GIS) to map the location of the hybrid zone, which follows a direct route between two lakes, as would be anticipated from tension zone theory. Even within the central area of the hybrid zone, there is a much higher frequency of pure race individuals than hybrid, making this a clear example of a bimodal zone in the sense of Jiggins & Mallet (2000). The zone runs through good habitat for common shrews, but nevertheless it is very narrow (standard cline widths: 3-4 km), as would be anticipated from low hybrid fitness. There is clear potential for an interruption to gene flow and build-up of reproductive isolation. As found in some other hybrid zones, there is a high frequency of novel genetic variants, in this case, new chromosomal rearrangements. Here, we report a de novo Robertsonian fission and a de novo reciprocal translocation, both for the first time in the common shrew. There is an extraordinarily high frequency of de novo mutations recorded in F1 hybrids in the zone and we discuss how chromosomal instability may be associated with such hybrids. The occurrence of a de novo Robertsonian fission is of considerable significance because it provides missing evidence that fissions are the basis of the novel acrocentric forms found and apparently selected for in certain common shrew hybrid zones.

Colonization of Ireland: revisiting 'the pygmy shrew syndrome' using mitochondrial, Y chromosomal and microsatellite markers.

There is great uncertainty about how Ireland attained its current fauna and flora. Long-distance human-mediated colonization from southwestern Europe has been seen as a possible way that Ireland obtained many of its species; however, Britain has (surprisingly) been neglected as a source area for Ireland. The pygmy shrew has long been considered an illustrative model species, such that the uncertainty of the Irish colonization process has been dubbed 'the pygmy shrew syndrome'. Here, we used new genetic data consisting of 218 cytochrome (cyt) b sequences, 153 control region sequences, 17 Y-intron sequences and 335 microsatellite multilocus genotypes to distinguish between four possible hypotheses for the colonization of the British Isles, formulated in the context of previously published data. Cyt b sequences from western Europe were basal to those found in Ireland, but also to those found in the periphery of Britain and several offshore islands. Although the central cyt b haplotype in Ireland was found in northern Spain, we argue that it most likely occurred in Britain also, from where the pygmy shrew colonized Ireland as a human introduction during the Holocene. Y-intron and microsatellite data are consistent with this hypothesis, and the biological traits and distributional data of pygmy shrews argue against long-distance colonization from Spain. The compact starburst of the Irish cyt b expansion and the low genetic diversity across all markers strongly suggests a recent colonization. This detailed molecular study of the pygmy shrew provides a new perspective on an old colonization question.

The role of dual time point FDG PET imaging in the evaluation of solitary pulmonary nodules with an initial standard uptake value less than 2.5.

AIM: To evaluate the accuracy of dual time point 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) imaging in the evaluation of the mildly metabolic solitary pulmonary nodule (SPN) and to assess whether accuracy could be improved by delaying second image acquisition to 180 minutes. MATERIALS AND METHODS: Fifty-four patients were included in the study. Thirty-six had an SUV(max) <2.5 at 60 min. For these patients, two methods of interpreting the subsequent delayed FDG PET imaging at 180 min were investigated. The first method analysed the SUV(max) of SPNs on delayed imaging, in which an SUV(max) of 2.5 or more was regarded as a criterion for malignancy. The second method was retention index (RI) analysis, in which an increase of 10% or more in SUV(max) between the initial and delayed images, was regarded as an indication of malignancy. RESULTS: For the group as a whole (n=54), the sensitivity, specificity and accuracy of using an SUV(max) of 2.5 or more as an indication of malignancy at the time of initial image acquisition (60 min) was 58, 89, and 74%, respectively. For SPNs that had an initial SUV(max) <2.5 (n=36), the sensitivity, specificity, and accuracy of using an SUV(max) of 2.5 or more as a criterion for malignancy on the delayed image acquisition (180 min), was 36, 96, and 78% respectively. However, if an RI of >10% was used as a criterion for malignancy between the initial and delayed images, the sensitivity, specificity, and accuracy was 73, 80, and 78%, respectively. These results are similar to a recent paper, where image acquisition occurred at 60 and 120 min post-tracer injection. CONCLUSION: Dual time point FDG PET imaging with RI analysis, is a useful technique in evaluating SPN with an initial SUV(max) <2.5. Prolonging second image acquisition from 120 to 180 min does not appear to improve the accuracy of this technique. However, given that maximal FDG uptake by lung carcinomas is thought to be in the region of 5h, it may be that improving the accuracy of dual time point FDG PET imaging requires a more significant delay in second image acquisition in this specific subgroup.

Biomarkers in acute coronary syndrome and percutaneous coronary intervention.

The universal definition of myocardial infarction has proved how important the role of biomarkers in the assessment of acute coronary syndrome (ACS) has become. As a result, management of patients with ACS today is more specific and personalized than ever, but there is still a lot of room for improvement. Unmet needs for a faster and more specific rule-in and rule-out of myocardial infarction, for a pronounced risk assessment allowing for standardized guidelines on personalized therapy and for an effective monitoring of our therapeutic efforts to guarantee an optimal risk-benefit turnout still require intensive biomarker research and clinical validation. This review addresses a set of cardiovascular biomarkers with different pathophysiological backgrounds and discusses their diagnostic, prognostic and therapeutic value in the setting of ACS and percutaneous coronary intervention (PCI). The article provides a review of the current knowledge and literature on biomarkers in ACS and PCI, discussing currently used biomarkers like cardiac troponin (cTN), high sensitive cardiac troponin (hscTn), natriuretic peptides (NPs) as well as promising future biomarkers like copeptin, choline and lipoprotein-associated phospholipase A2 (LP-PLA2). The review concentrates on the clinical application of these markers, evaluating not only their diagnostic and prognostic value but also their integrability into routine practice. There are currently a number of new biomarkers and new biomarker assays under investigation which give hope for a much improved diagnostic and risk stratification process. Large diagnostic clinical trials are still needed to evaluate their impact on ACS patient management and subsequent PCI in clinical practice.

New metacentric population of the house mouse (Mus musculus domesticus) found in Valchiavenna, Northern Italy.

Although the standard karyotype of the western house mouse (Mus musculus domesticus) consists entirely of telocentric chromosomes, there are over 100 populations across western Europe and North Africa characterized by different sets of metacentrics formed by Robertsonian fusions and whole-arm reciprocal translocations. Here we report the discovery of a new metacentric population from Valchiavenna, northern Italy, that we have named the 'Lower Valchiavenna population' (abbreviated as ILVC). This metacentric population is found in villages and on farms over a 10-kilometer stretch comprising the southern half of Valchiavenna. ILVC is characterized by the metacentrics 1.18, 2.4, 3.8, 5.15, 6.7, 9.14, 10.12, 11.13 and 16.17, and appears to be closely related to the Chiasso population (CHCH), which possesses the same set of metacentrics except 1.18. We discuss the evolutionary origin of ILVC in relation to human occupation of the region. We also suggest that the geographical position of ILVC between 2 other metacentric populations with entirely different sets of metacentrics (Chiavenna, ICHI, and lower Valtellina, ILVA) may provide 2 additional chromosomal hybrid zones for the study of speciation.