Unexplained Mortality Research Articles

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.

Clinico-pathology, diagnosis and management of Cysticercus fasciolaris and Hymenolepis diminuta co-infection in wistar rats.

Aim:The present study was undertaken to study the pathology and control of sudden unexplained mortality in wistar rats.Materials and Methods:This study was conducted in a colony of 25 male wistar rats where there was mortality of nine rats. The dead rats were subjected to thorough post-mortem examination and necropsy samples were processed for hematoxylin and eosin staining for histopathological studies. Faecal samples of live rats were studied for the presence of parasitic eggs. Treatment with anthelmintics was given to manage the mortality and infections.Results:The investigation revealed a natural co-infection of Cysticercus fasciolaris and Hymenolepis diminuta in wistar rats, which were pathogenic enough to cause mortality. Typical lesions associated with the parasites were found in the dead rats. The mortality and infection were managed with common anthelmintics.Conclusion:C. fasciolaris and H. diminuta infection can cause mortality in wistar rats even when individually they cause asymptomatic infection. The mortality and infection can be managed with common anthelmintics.

MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

PurposeColon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Patients and MethodsCancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.ResultsOf 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.ConclusionsAnalysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.Trial RegistrationClinicalTrials.gov NCT00003835

Bedaquiline: a novel antitubercular agent for the treatment of multidrug-resistant tuberculosis.

Bedaquiline is a diarylquinoline antitubercular drug with a novel mechanism of action against Mycobacterium tuberculosis. Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents in more than 40 years. Bedaquiline is indicated for the treatment of multidrug-resistant tuberculosis (MDR TB) in combination with at least three other antitubercular drugs when no other effective regimen is available. The recommended bedaquiline dosage is 400 mg orally once/day for 2 weeks followed by 200 mg orally 3 times/week for 22 weeks. Bedaquiline should be administered with food, which increases the bioavailability 2-fold. Bedaquiline is metabolized by cytochrome P450 isoenzyme 3A4 and is impacted by both inducers and inhibitors of this isoenzyme. Concentration-dependent bactericidal activity was observed in laboratory and murine studies. Accelerated approval was granted in the United States and European Union based on the results of two phase IIb clinical studies that used sputum culture clearance as a surrogate end point for clinical efficacy. These studies showed greater sputum culture clearance up to week 24 for the bedaquiline group compared with placebo. Common adverse events in clinical trials included nausea, arthralgia, and headache. Serious adverse events included elevated serum transaminase levels and rate-corrected QT-interval prolongation. Unexplained higher mortality was seen in patients receiving bedaquiline versus those receiving placebo. Bedaquiline is a novel agent with a unique mechanism of action and has the potential to meet a great need in patients with MDR TB who have no other treatment options. Due to safety concerns and limited clinical information, phase III trials are needed to fully determine its place in therapy.

Improving early detection of exotic or emergent oyster diseases in France: Identifying factors associated with shellfish farmer reporting behaviour of oyster mortality

Farmers’ vigilance is essential for the detection of epidemics, including potential emerging diseases, in marine shellfish. A field study was conducted to investigate oyster farmers’ reporting practices and behaviour, and to identify factors influencing the reporting process of oyster mortality, with the ultimate aim of improving early detection of unexplained oyster mortality outbreaks.A retrospective case-control study of oyster farmers from Charente-Maritime (France) was designed, based on interviews with 27 non-reporting and 89 reporting farmers, further split into 40 formerly-reporting and 49 currently-reporting farmers. Information about farmer and farm characteristics, farming practices, farm health history and related financial compensation on the farm, knowledge of the mortality reporting system and reporting behaviour was collected. Sampling design was considered in the calculations and farmers’ reporting behaviour was modelled using an ordinal logistic regression (continuation-ratio model).Notification procedures were fairly well known among farmers and the reporting system was well accepted overall. Nevertheless, a lack of awareness of the aims of the reporting system was revealed, which contributed to late reporting. Factors identified as driving a farmer's decision to report oyster mortality concerned their lack of awareness of mortality reporting (production type, farm size, location of the production cycle, accessibility of the leasing grounds) and willingness to report (possibility and extent of financial compensation, a feeling of not being involved, whether it was first year of reporting). Overall classification performance of the model built in this study was 64%. In particular, financial compensation for oyster production losses appeared to be a clear incentive for reporting, but was countered by a habituation effect combined with a lack of awareness of the aims of the reporting system: oyster farmers looking for benefits for themselves in reporting, rather than early detection of a disease outbreak.Both economic compensation and the farmers’ non-economic values and perceptions should be considered to improve oyster farmers’ reporting compliance and sustainability of the reporting system. Education and participatory approaches could help to change these attitudes and thus improve oyster farmers’ compliance with reporting duties, resulting in improved early detection of epidemics and emerging or exotic oyster diseases.

Detection of the emerging amphibian pathogens Batrachochytrium dendrobatidis and ranavirus in Russia.

In a population of the European common toad Bufo bufo from a rural pond in the region of Lake Glubokoe Regional Reserve in Moscow province, Russia, unexplained mass mortality events involving larvae and metamorphs have been observed over a monitoring period of >20 yr. We tested toads from this and a nearby site for the emerging amphibian pathogens Batrachochytrium dendrobatidis (Bd) and ranavirus (Rv). Both pathogens were detected, and at the rural pond site, with the above-noted losses and decline in toad breeding success, 40% of B. bufo metamorphs were Bd positive, 46% were Rv positive and 20% were co-infected with both pathogens. Toad metamorphs from a neighbouring water body were also Bd and Rv positive (25 and 55%, respectively). This is the first confirmation of these pathogens in Russia. Questions remain as to the origins of these pathogens in Russia and their roles in documented mass mortality events.

Vulnerability of neonatal respiratory neural control to sustained hypoxia during a uniquely sensitive window of development

The first postnatal weeks represent a period of development in the rat during which the respiratory neural control system may be vulnerable to aberrant environmental stressors. In the present study, we investigated whether sustained hypoxia (SH; 11% O2) exposure starting at different postnatal ages differentially modifies the acute hypoxic (HVR) and hypercapnic ventilatory response (HCVR). Three different groups of rat pups were exposed to 5 days of SH, starting at either postnatal age 1 (SH1-5), 11 (SH11-15), or 21 (SH21-25) days. Whole body plethysmography was used to assess the HVR and HCVR the day after SH exposure ended. The primary results indicated that 1) the HVR and HCVR of SH11-15 rats were absent or attenuated (respectively) compared with age-matched rats raised in normoxia; 2) there was a profoundly high (∼84% of pups) incidence of unexplained mortality in the SH11-15 rats; and 3) these phenomena were unique to the SH11-15 group with no comparable effect of the SH exposure on the HVR, HCVR, or mortality in the younger (SH1-5) or older (SH21-25) rats. These results share several commonalities with the risk factors thought to underlie the etiology of sudden infant death syndrome, including 1) a vulnerable neonate; 2) a critical period of development; and 3) an environmental stressor.

Bedaquiline

To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and administration of bedaquiline, a novel oral diarylquinoline antimycobacterial agent approved by the Food and Drug Administration for the treatment of adults with pulmonary multidrug-resistant tuberculosis (MDR-TB). A search of PubMed (January 2004-May 2013) and International Pharmaceutical Abstracts (January 2004-May 2013) using the search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included proceedings of the Union World Conference on Lung Health. Preclinical data as well as Phase 1 and 2 studies published in English were evaluated. Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase. Clinical trials have been conducted evaluating the use of bedaquiline in combination with a background regimen for the treatment of adults with pulmonary MDR-TB. Bedaquiline has an excellent in vitro activity against Mycobacterium tuberculosis, including multidrug resistant M tuberculosis; however, its side effect profile limits its use against MDR-TB when no other effective regimen can be provided. Bedaquiline carries Black Box warnings for increased risk of unexplained mortality and QT prolongation. Bedaquiline is metabolized via the CYP3A4 isoenzyme and thus interacts with rifamycins and several antiretrovirals. In an era of emerging resistance and given the suboptimal efficacy and toxicity of currently available regimens for MDR-TB, bedaquiline represents a great addition to the existing armamentarium of anti-TB agents particularly in areas of the world where the disease is endemic.

Long QT Interval in Turner Syndrome – A High Prevalence of LQTS Gene Mutations

ObjectivesQT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype.MethodsAdult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett’s (bQTc) and Hodges’s formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done.ResultsThe mean hQTc in women with Turner syndrome (414.0±25.5 ms) compared to controls (390.4±17.8 ms) was prolonged (p<0.001) and did not change over time (416.9±22.6 vs. 415.6±25.5 ms; p = 0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2±24.8 vs. 407.6±25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2).ConclusionThere is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women.Clinical Trial RegistrationNCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

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Does height of exposure in the canopy influence egg mortality in Acanthoscelides macrophthalmus (Coleoptera: Chrysomelidae), a biological control agent of Leucaena leucocephala in South Africa?

Introduced into several countries worldwide for agroforestry, Leucaena leucocephala (Lam.) de Wit is a typical ‘conflict species’ that invades several riparian, forested and disturbed habitats in South Africa. The seed beetle Acanthoscelides macrophthalmus (Schaeffer) (Chrysomelidae: Bruchinae) was subsequently deployed as a seed-reducing agent to offset its excessive seed output. However, exploratory egg-exposure trials, in which native Acacia s.l. trees were used as ‘surrogate host plants’, suggested that high egg mortality is reducing the beetle's impact. The aims of this study were to (1) verify this suspicion by comparing the mortality of eggs exposed in L. leucocephala and Acacia nilotica (L.) Willd ex Del. stands and (2) determine whether height of exposure in the canopy (i.e. oviposition site selection) influences the different mortality factors. Although lower than in the exploratory trials, egg mortality was considerable, ranging from 30 to 50% in most instances. While unaffected by height of exposure, the overall egg mortality (i.e. all factors) was significantly lower in seeds exposed on L. leucocephala. Mortality was not only mostly attributed to parasitism (51% of mortality), but also predation (30%) and unknown factors (19%). While unexplained mortality and predation were not influenced by tree species or height of exposure, parasitism increased significantly with height above ground and was significantly lower in seeds exposed on L. leucocephala. Egg mortality is thus one of several factors that appears to be limiting the efficacy of A. macrophthalmus in South Africa.

A Functional Thrombopoietin Receptor Is Required for Full Expression of Phenotype in a JAK2 V617F Transgenic Mouse Model of Polycythemia Vera

Abstract 427Polycythemia vera (PV) is a clonal stem cell disorder in which there is overproduction of red cells, white cells and platelets, extramedullary hematopoiesis and transformation to myelofibrosis. Enhanced hematopoiesis in PV is due to constitutive activation of JAK2, the cognate tyrosine kinase of type I cytokine receptors such as the erythropoietin and thrombopoietin receptors. Hematopoietic stem cells express the thrombopoietin receptor (Mpl) but paradoxically mice lacking the MPL gene exhibit only thrombocytopenia while maintaining the capacity to not only substantially elevate their platelet and leukocyte counts during marrow reproductive stress but also the number of multipotent and committed hematopoietic progenitor cells as well. Equally paradoxical, Mpl expression is impaired in PV, but how impaired expression of a master regulator of stem cell function could be associated with a global increase in hematopoiesis has been a conundrum. Recently, data were presented (Blood 119: 4625, 2012) suggesting that Mpl down regulation in PV was due to constitutive JAK2 activation, which abrogated the antiproliferative effects of the high plasma thrombopoietin (TPO) levels in PV, thus sustaining the PV phenotype. We have used a JAK2 V617F transgenic mouse model (V617Ftg) (Blood 111:5109, 2009) to examine the role of Mpl in the pathogenesis of the JAK2 V617F-positive PV phenotype and have observed that deletion of the MPL gene ameliorated the PV phenotype in this model, reducing the hemoglobin level, leukocyte and platelet counts and splenomegaly and reversing marrow fibrosis, while the presence of a single MPL gene was sufficient to restore the PV phenotype. However, total deletion of the MPL gene does not perfectly model human PV where Mpl is present but quantitatively reduced. Therefore, we examined the effect of manipulating Mpl behavior in vivo by modifying Mpl signaling while maintaining Mpl expression, first, by eliminating TPO production, and second, by expressing a functionally impaired Mpl receptor, and as a control, specifically impairing megakaryocyte differentiation alone. To this end, we crossbred the V617Ftg PV mouse with a TPO gene knockout mouse (TPO ko), with a mouse homozygous for the MPL mutation, C40R (C40R hom), which in the homozygous state causes thrombocytopenia, and finally, with an MKL1 knockout mouse (MKL1ko) that is thrombocytopenic due to impaired megakaryocyte maturation. Crossbreeding produced the three expected genotypes (JAK2 V617F/TPO ko, JAK2 V617F/C40R hom and JAK2 V617F/MKL1ko) without unexplained mortality or impoverished growth. We compared the blood counts, spleen weights and bone marrow and spleen histology of these three genotypes with each other and with JAK2 V617F/TPO heterozygous (het) mice over a 33 week period. The natural history of the V617Ftg PV mouse is one of initial erythrocytosis, thrombocytosis, leukocytosis, splenomegaly, and expansion of short term marrow repopulating cells (ST-HSC), common myeloid progenitor cells (CMP) and marrow and spleen committed hematopoietic progenitor cells (HPC)(CFU-GEMM, CFU-GM, BFU-E, CFU-E and CFU-MK), and myelofibrosis with a subsequent decline in erythrocytosis. Abrogating TPO production in the V617Ftg PV mouse normalized the platelet and leukocyte counts, delayed the development of erythrocytosis, reduced spleen size and ST-HSC, CMP, and all marrow and spleen committed HPC compartments and reversed marrow fibrosis. The V617Ftg PV - C40R MPL cross prevented thrombocytosis, erythrocytosis, leukocytosis and splenomegaly, and reduced all the marrow and spleen committed HPC compartments. By contrast, the V617Ftg PV-MKL1 ko cross slowed the rate of rise of the platelet count and hemoglobin level but had no effect on splenomegaly or marrow fibrosis, nor was there a reduction in any of the marrow or spleen committed HPC. Expression of one TPO gene by crossing the V617Ftg PV mouse with mice heterozygous for the TPO gene (JAK2 V617F/TPO het) restored the PV phenotype. In conclusion, while it is unquestioned that JAK2 V617F is necessary for expression of the PV phenotype, our data indicate that it alone is insufficient and requires not only the expression of a functional TPO receptor but also receptor activation by its cognate ligand TPO. This latter observation suggests that interfering with the TPO-Mpl interaction could be of therapeutic value in the treatment of human PV. Disclosures:No relevant conflicts of interest to declare.

A Comparison of Administrative and Physiologic Predictive Models in Determining Risk Adjusted Mortality Rates in Critically Ill Patients

BackgroundHospitals are increasingly compared based on clinical outcomes adjusted for severity of illness. Multiple methods exist to adjust for differences between patients. The challenge for consumers of this information, both the public and healthcare providers, is interpreting differences in risk adjustment models particularly when models differ in their use of administrative and physiologic data. We set to examine how administrative and physiologic models compare to each when applied to critically ill patients.MethodsWe prospectively abstracted variables for a physiologic and administrative model of mortality from two intensive care units in the United States. Predicted mortality was compared through the Pearsons Product coefficient and Bland-Altman analysis. A subgroup of patients admitted directly from the emergency department was analyzed to remove potential confounding changes in condition prior to ICU admission.ResultsWe included 556 patients from two academic medical centers in this analysis. The administrative model and physiologic models predicted mortalities for the combined cohort were 15.3% (95% CI 13.7%, 16.8%) and 24.6% (95% CI 22.7%, 26.5%) (t-test p-value<0.001). The r2 for these models was 0.297. The Bland-Atlman plot suggests that at low predicted mortality there was good agreement; however, as mortality increased the models diverged. Similar results were found when analyzing a subgroup of patients admitted directly from the emergency department. When comparing the two hospitals, there was a statistical difference when using the administrative model but not the physiologic model. Unexplained mortality, defined as those patients who died who had a predicted mortality less than 10%, was a rare event by either model.ConclusionsIn conclusion, while it has been shown that administrative models provide estimates of mortality that are similar to physiologic models in non-critically ill patients with pneumonia, our results suggest this finding can not be applied globally to patients admitted to intensive care units. As patients and providers increasingly use publicly reported information in making health care decisions and referrals, it is critical that the provided information be understood. Our results suggest that severity of illness may influence the mortality index in administrative models. We suggest that when interpreting “report cards” or metrics, health care providers determine how the risk adjustment was made and compares to other risk adjustment models.

Moving-Average Trigger for Early Detection of Rapidly Increasing Mortality in Caged Table-Egg Layers

Rapidly increasing and unexplained mortality in commercial poultry flocks may signal the presence of a highly transmissible and reportable disease. Activation of an infectious-disease surveillance system occurs when a key production parameter, i.e., mortality, changes. Various triggers have been proposed to alert producers when mortality exceeds normal limits for a given production system to enable early detection of such diseases. In this article we demonstrate that a simple moving-average trigger is useful for detecting any disease syndrome in caged table-egg layer flocks that manifests itself as sudden, rapidly increasing mortality. We superimposed HPAI disease mortality output data derived from a disease transmission model and from a naturally occurring HPAI outbreak onto normal mortality data from 12 healthy commercial egg-layer flocks, and compared the performance of 7-day moving-average triggers to previously proposed triggers. The moving-average trigger is more efficient, resulting in fewer false-positive alerts and an earlier time to disease detection. It can be easily calculated by using a computer spreadsheet providing only 7 days of mortality data and can be practically and inexpensively implemented by large commercial poultry integrators. A moving-average trigger can be an active component of a production-based surveillance system.

Seasonal Comparison of Physiological Adaptation and Growth of Suminoe (Crassostrea ariakensis) and Eastern (Crassostrea virginica) Oysters

Shell growth, survival, and physiology were compared between diploid Suminoe (Crassostrea ariakensis) and eastern oysters (Crassostrea virginica) under conditions simulating a U.S. subtropical estuary. Two age groups (4 mo and 28 mo) of both oyster species were grown for 9 mo (December 2006 through August 2007) in quarantine mesocosms (700 L) supplied with ambient flowing (≥ 10 L/min) water (annual temperature range, 18.6–30.4°C; salinity, 28–37.7). There was no difference in overall rates of shell growth between the 2 oyster species over the 9-mo period. Specific growth rates for C. ariakensis did not differ over time, but they did for C. virginica. The growth rate of C. virginica was slowest in the winter (8.9 × 10-4 mm2/day) and fastest in the spring (43.5 × 10-4 mm2/day). Mortality of both species rose abruptly in April 2007, and all (100%) remaining C. ariakensis were dead by the end of the study. Although 28% of the remaining C. virginica died in April 2007, there was little further mortality in this species before the study was terminated in August 2007. Physiological responses of both species of oysters were compared under seasonal temperate euhaline quarantine conditions to understand better how temperature affects these species without the confounding unexplained mortality encountered in the subtropical mesocosms. The clearance rate of C. ariakensis (1.2 L/g/h) was half that of C. virginica (2.2 L/g/h) during the summer (25°C); however, respiration rates for C. ariakensis (2.6 ml O2/g/h) and C. virginica (2.5 ml O2 g/h) were similar. The low clearance rate of C. ariakensis during the summer resulted in a negative scope for growth (-36.2 J/g/h) during this season. During the winter, C. ariakensis remained physiologically active when water temperatures were as low as 2°C; C. virginica were quiescent during this time. We conclude that the “Oregon” strain of C. ariakensis tested will not thrive in the warm subtropical waters of the U.S. southeastern coast; however, given its native range in Asia, we do not discount the possibility of an adaptation to warmer temperatures over time.

Bottom-up trophic cascades caused by moose browsing on a natural enemy of a galling insect on balsam fir

To elucidate the impact of browsing by moose on the indigenous insect community, we investigated the abundance of a specialist insect herbivore (galler; Paradiplosis tumifex) and its natural enemy (inquiline; Dasineura balsamicola) on balsam fir saplings in the field using exclosures in Newfoundland, Canada. The number of current-year shoots on each sapling, but not the density of balsam fir saplings, was significantly higher inside exclosures, where moose had been excluded for 9–12 years, than outside exclosures. Current-year shoots were longer and contained more, but smaller, needles inside than outside exclosures. Moose browsing had a negative impact on the abundance of both the galler and its natural enemy. Gall density was 85.6% and 60.4% lower in 2006 and 2007, respectively, outside than inside exclosures. Similarly, the attack rate of D. balsamicola was 76.5% lower outside than inside exclosures in 2007. The apparent survival rate of P. tumifex larvae was similar outside and inside exclosures due to higher rates of unexplained mortality in galls outside exclosures. Survival of P. tumifex larvae was positively related to shoot length and inversely related to gall density. Only gall density was negatively related to D. balsamicola survival. Our results demonstrate that a large mammal can cause strong bottom-up trophic cascades.

The Impact of Neoliberal “Political Attack” on Health: The Case of the “Scottish Effect”

The health impact of neoliberal "shock treatment" has been explored in relation to the former USSR, but much remains to be done to ascertain its impact elsewhere. The authors consider the "Scottish Effect" in health-the unexplained excess mortality in Scotland, compared with the rest of Britain, after accounting for deprivation. A prevalent but as yet untested view is that this effect is linked to the neoliberal "political attack" against the organized working class, implemented by the post-1979 U.K. Conservative governments. The article begins to develop and test this view in the form of a "political attack hypothesis". It shows how the west of Scotland became a particular target for the political attack planned by the U.K. Conservative Party prior to its election in 1979; outlines how such an attack might affect health; and shows that after 1979 the United Kingdom as a whole was exposed to neoliberalism in a way other European nations were not and, crucially, that the west of Scotland was more vulnerable to its damaging effects than other U.K. regions. The authors conclude that it is now appropriate to explore more fully the role of neoliberal political attack in creating the "Scottish Effect" in health.

Water quality and microbial community structure in juvenile Atlantic cod ( Gadus morhua L.) cultures

The effect of water treatment and flow rate on young Atlantic cod juveniles was investigated in a 36-days experiment. Four different flow rates (10, 20, 40, and 70 times the effective tank volume per day) were set up in triplicate tanks within each of three rigs with recirculated, UV-radiated, and untreated water, respectively. Each of the 36 tanks was stocked with 200 weaned cod juveniles at a mean weight of 0.048 g. Fish mortality was recorded daily in all tanks, and growth (wet weight) was determined at the end of the experiment. The microflora in the rearing water was investigated by means of PCR-DGGE and flow cytometry. Observed mortality was significantly higher at low flow rates while otherwise unexplained mortality (presumed to be due to cannibalism) was lowest in the recirculation system. No correlation was found between survival and growth. Growth was significantly affected by both water exchange rate and treatment, as the juveniles from high flow rates and the UV-treatment showed elevated growth rates. Both growth and survival scaled in accordance with metabolic factors like oxygen saturation and unionized ammonia. Bacterial concentrations increased in all tanks and treatment from the beginning of the experiment to the end. The UV-treated and untreated water started at typical seawater concentrations (0.5–1 × 10 6 mL −1) and increased five to tenfold during the experiment. The recycled water tanks started with bacterial concentrations 2–5 times higher than the UV- and untreated experiments at the time of fish transfer, and ended up with 10 times higher concentrations in the end. Cluster analysis of the DGGE profiles separated the recirculation tanks, including the respective inlet water, from the flow-through systems, with one exception (the highest flow rate). Eighty-five% of the sequences clustered within the Gammaproteobacteria, further divided into four distinct clusters. One of the clusters was only detected in the recirculation system, and showed highest affiliation to bacteria belonging to the Alteromonas/Pseudoalteromonas genera. In contrast, bacteria belonging to the family Vibrionaceae were detected in the flow-through systems.

Nest Establishment, Pollination Efficiency, and Reproductive Success ofMegachile rotundata(Hymenoptera: Megachilidae) in Relation to Resource Availability in Field Enclosures

The alfalfa leafcutting bee, Megachile rotundata (Fabricius), is used to pollinate alfalfa, Medicago sativa L., for seed production in the United States and Canada. It is difficult to reliably sustain commercial M. rotundata populations in the United States because of problems with disease, parasites, predators, and unexplained mortality. One possible explanation for early immature mortality is that, relative to floral availability, superfluous numbers of bees are released in alfalfa fields where resources quickly become limited. Our objective was to determine how M. rotundata density affects bee nesting, pollination efficiency, and reproductive success. Various numbers of bees were released into enclosures on an alfalfa field, but only 10-90% of released female bees established nests. Therefore, a "bee density index" was derived for each enclosure from the number of established females and number of open flowers over time. As the density index increased, significant reductions occurred in the number of pollinated flowers, number of nests, and number of cells produced per bee, as well as the percentage of cells that produced viable prepupae by summer's end and the percentage that produced adult bees. The percentage of cells resulting in early brood mortality (i.e., pollen balls) significantly increased as the density index increased. We conclude that bee nest establishment, pollination efficiency, and reproductive success are compromised when bee densities are high relative to floral resource availability. Open field studies are needed to determine commercial bee densities that result in sustainable bee populations and adequate pollination for profitable alfalfa seed production.

Development and distribution of the non-indigenous Pacific oyster (Crassostrea gigas) in the Dutch Wadden Sea

Pacific oysters (Crassostrea gigas) were first observed in the Dutch Wadden Sea near Texel in 1983. The population increased slowly in the beginning but grew exponentially from the mid-1990s onwards, although now some stabilisation seems to be occurring. They occur on a variety of substrates such as mussel beds (Mytilus edulis), shell banks, dikes and poles. After initial settlement spat may fall on older individuals and congregate to dense clumps and subsequently form reefs. Individual Pacific oysters grow 3–4 cm long in their first year and 2–3 cm in their second year. Many mussel beds (Mytilus edulis) are slowly taken over by Pacific oysters, but there are also several reports of mussel spat settling on Pacific oyster reefs. This might in the end result in combined reefs. Successful Pacific oyster spat fall seems to be related to high summer temperatures, but also after mild summers much spat can be found on old (Pacific oyster) shells. Predation is of limited importance. Mortality factors are unknown, but every now and then unexplained mass mortality occurs. The gradual spread of the Pacific oyster in the Dutch Wadden Sea is documented in the first instance based on historical and anecdotal information. At the start of the more in-depth investigation in 2002, Pacific oysters of all size classes were already present near Texel. Near Ameland the development could be followed from the first observed settlement. On dense reefs each square metre may contain more than 500 adult Pacific oysters, weighing more than 100 kg per m² fresh weight.