Invasion genetics and development of rapid diagnostics of insect pests on traded plants

Background: Global trade of plant products is a major driving force for the unintended spread of economically harmful insect pests. This PhD thesis aimed at (i) developing and implementing molecular tools for the on-site identification of invasive insect pests at points of entry (POEs) for plant import products as a prevention measure; and (ii) investigating the invasion history of the mosaic leafhopper Orientus ishidae, a potential vector of grapevine Flavescence dorée phytoplasma. Methods: To achieve the first goal, loop-mediated isothermal amplification (LAMP)-based genetic assays for the rapid on-site identification of Bemisia tabaci, Thrips palmi and several invasive fruit flies of the genera Bactrocera and Zeugodacus were developed. Using publicly available DNA sequences, LAMP primers were designed to specifically target a fragment of the mitochondrial cytochrome c oxidase subunit 1 gene. To address the second goal of this PhD thesis, the invasion genetics of O. ishidae was studied, an invasive insect species that spread from its native range from in East Asia to North America in the first half of the 20th century and only recently colonised Europe. Possible source populations and invasion pathways were investigated by assessing the genetic structure of 41 O. ishidae populations from Asia, Europe, and North America based on a mitochondrial marker and 641 single nucleotide polymorphisms (SNPs) generated by double digest restriction-site associated DNA (ddRAD) sequencing. Results: Validation performed under laboratory and on-site conditions demonstrated the robustness and reliability of the developed LAMP identification assays. Analysing 319 insect specimens, the overall diagnostic test efficiency was 98% and the overall diagnostic test specificity was 100%. The small number of false-negative results (2%) originated either from previously unknown biotypes, not included in the initial primer design, or from handling errors during LAMP preparation. The results from the molecular genetic analyses of O. ishidae revealed a clear genetic separation between a native population from Asia and the non-native populations from Europe and North America. Among the non-native populations, only faint signals of spatial genetic structuring were found. However, when comparing non-native populations from Europe and North America, elevated levels of admixture of genetically distant mitochondrial haplotypes were observed for European populations. Conclusion: Characterised by high analysis speed (<1 h) and simplicity in use (only 1 pipetting step), the validated LAMP assays were found to be suitable identification tools for on-site application by plant health inspectors. Since completion of the validation phase, the developed identification assays are routinely deployed in the phytosanitary import control process of Switzerland. The considerable genetic separation between native and non-native populations of O. ishidae together with the strikingly high genetic similarity of European and North American populations suggest an invasion scenario in which North American populations served as source for the European invasion. A slightly reduced genetic structure combined with increased admixture of genetically distant mitochondrial haplotypes furthermore indicate that the European colonisation history was shaped by multiple introductions from North America, complemented by frequent intra-European gene flow. Taken together, it is hypothesised that the overall genetic complexity of non-native populations was strongly driven by frequent international trade of plants infested by O. ishidae

Saproxylic species are linked to the amount and isolation of dead wood across spatial scales in a beech forest

ContextDead wood is a key habitat for saproxylicspecies, which are often used as indicators of habitatquality in forests. Understanding how the amount andspatial distribution of dead wood in the landscapeaffects saproxylic communities is therefore importantfor maintaining high forest biodiversity.ObjectivesWe investigated effects of the amountand isolation of dead wood on the alpha and betadiversity of four saproxylic species groups, with afocus on how the spatial scale influences results.MethodsWe inventoried saproxylic beetles, wood-inhabiting fungi, and epixylic bryophytes and lichenson 62 plots in the Sihlwald forest reserve in Switzer-land. We used GLMs to relate plot-level speciesrichness to dead wood amount and isolation on spatialscales of 20–200 m radius. Further, we used GDMs todetermine how dead wood amount and isolationaffected beta diversity.ResultsA larger amount of dead wood increasedbeetle richness on all spatial scales, while isolation hadno effect. For fungi, bryophytes and lichens this wasonly true on small spatial scales. On larger scales ofour study, dead wood amount had no effect, whilegreater isolation decreased species richness. Further,we found no strong consistent patterns explaining betadiversity

Extended discussion platform on international forest policy (IDANE Wald+) in Switzerland

Peer reviewe

Development of the Gastrointestinal Dysfunction Score (GIDS) for critically ill patients – A prospective multicenter observational study (iSOFA study)

Background & aims: To develop a five grade score (0–4 points) for the assessment of gastrointestinal (GI) dysfunction in adult critically ill patients. Methods: This prospective multicenter observational study enrolled consecutive adult patients admitted to 11 intensive care units in nine countries. At all sites, daily clinical data with emphasis on GI clinical symptoms were collected and intra-abdominal pressure measured. In five out of 11 sites, the biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) were measured additionally. Cox models with time-dependent scores were used to analyze associations with 28- and 90-day mortality. The models were estimated with stratification for study center. Results: We included 540 patients (224 with biomarker measurements) with median age of 65 years (range 18–94), the Simplified Acute Physiology Score II score of 38 (interquartile range 26–53) points, and Sequential Organ Failure Assessment (SOFA) score of 6 (interquartile range 3–9) points at admission. Median ICU length of stay was 3 (interquartile range 1–6) days and 90-day mortality 18.9%. A new five grade Gastrointestinal Dysfunction Score (GIDS) was developed based on the rationale of the previously developed Acute GI Injury (AGI) grading. Citrulline and I-FABP did not prove their potential for scoring of GI dysfunction in critically ill. GIDS was independently associated with 28- and 90-day mortality when added to SOFA total score (HR 1.40; 95%CI 1.07–1.84 and HR 1.40; 95%CI 1.02–1.79, respectively) or to a model containing all SOFA subscores (HR 1.48; 95%CI 1.13–1.92 and HR 1.47; 95%CI 1.15–1.87, respectively), improving predictive power of SOFA score in all analyses. Conclusions: The newly developed GIDS is additive to SOFA score in prediction of 28- and 90-day mortality. The clinical usefulness of this score should be validated prospectively. Trial registration: NCT02613000, retrospectively registered 24 November 2015.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Impaired ABCA1/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration

Age-related macular degeneration (AMD) is a progressive disease of the retinal pigment epithelium (RPE) and the retina leading to loss of central vision. Polymorphisms in genes involved in lipid metabolism, including the ATP-binding cassette transporter A1 (), have been associated with AMD risk. However, the significance of retinal lipid handling for AMD pathogenesis remains elusive. Here, we study the contribution of lipid efflux in the RPE by generating a mouse model lacking ABCA1 and its partner ABCG1 specifically in this layer. Mutant mice show lipid accumulation in the RPE, reduced RPE and retinal function, retinal inflammation and RPE/photoreceptor degeneration. Data from human cell lines indicate that the AMD risk-conferring allele decreases expression, identifying the potential molecular cause that underlies the genetic risk for AMD. Our results highlight the essential homeostatic role for lipid efflux in the RPE and suggest a pathogenic contribution of reduced ABCA1 function to AMD

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Fabry's disease: otoneurologic findings in twelve members of one family

Fabry's disease corresponds to an inherited disorder transmitted by an X-linked recessive gene. It generates a dysfunction of glycosphingolipid metabolism due to an enzymatic deficiency of alpha-galactosidase activity, resulting in glycosphingolipid deposits in all areas of the body. The clinical (heart, kidney, and central nervous system) manifestations are more severe in hemizygous boys than in heterozygous girls. They appear during childhood or adolescence: acroparesthesia, joint pain, angiokeratoma, corneal dystrophy, hypohydrosis or anhydrosis, and renal failure. The otoneurologic symptoms consist of hearing fluctuation, progressive unilateral or bilateral hearing loss, and episodes of vertigo or dizziness. Otoneurologic findings in 12 of 26 members of the same family are presented: the mother and 9 of her 12 children, as well as 2 of her 14 grandchildren: 4 healthy persons, 4 heterozygous female carriers, and 4 hemizygous male patients. Three of the male patients had fluctuation of hearing, sudden hearing loss, and episodes of vertigo and dizziness. The otoneurologic examinations showed a bilateral cochleovestibular deficit (n = 1), a right cochleovestibular deficit (n = 1), and a bilateral hearing loss combined with a right vestibular deficit (n = 1). Histopathologic evidence of glycosphingolipid accumulation in vascular endothelial and ganglion cells, as well as atrophy of the stria and spiral ligament, might explain the otoneurologic symptoms and findings

Use of an on-demand drug-drug interaction checker by prescribers and consultants: A retrospective analysis in a Swiss teaching hospital

BACKGROUND: Offering a drug-drug interaction (DDI) checker on-demand instead of computer-triggered alerts is a strategy to avoid alert fatigue. OBJECTIVE: The purpose was to determine the use of such an on-demand tool, implemented in the clinical information system for inpatients. METHODS: The study was conducted at the University Hospital Zurich, an 850-bed teaching hospital. The hospital-wide use of the on-demand DDI checker was measured for prescribers and consulting pharmacologists. The number of DDIs identified on-demand was compared to the number that would have resulted by computer-triggering and this was compared to patient-specific recommendations by a consulting pharmacist. RESULTS: The on-demand use was analyzed during treatment of 64,259 inpatients with 1,316,884 prescriptions. The DDI checker was popular with nine consulting pharmacologists (648 checks/consultant). A total of 644 prescribing physicians used it infrequently (eight checks/prescriber). Among prescribers, internists used the tool most frequently and obtained higher numbers of DDIs per check (1.7) compared to surgeons (0.4). A total of 16,553 DDIs were identified on-demand, i.e., <10 % of the number the computer would have triggered (169,192). A pharmacist visiting 922 patients on a medical ward recommended 128 adjustments to prevent DDIs (0.14 recommendations/patient), and 76 % of them were applied by prescribers. In contrast, computer-triggering the DDI checker would have resulted in 45 times more alerts on this ward (6.3 alerts/patient). CONCLUSIONS: The on-demand DDI checker was popular with the consultants only. However, prescribers accepted 76 % of patient-specific recommendations by a pharmacist. The prescribers' limited on-demand use indicates the necessity for developing improved safety concepts, tailored to suit these consumers. Thus, different approaches have to satisfy different target groups

Musical Ear Syndrome and Cochlear Explantation: Case Report and Proposal for a Theoretical Framework.

OBJECTIVE To report an unusual case of musical ear syndrome, and to present a theoretical framework for this condition, merging information from the presented case and from former case reports. PATIENT A 67-year-old semi-professional musician, who underwent bilateral cochlear implantation and experienced musical ear syndrome, i.e., hearing music, where none was present. INTERVENTIONS Cochlear implantation with a bilateral cochlear implant, and cochlear explantation 17 months later. MAIN OUTCOME MEASURE Report of presence or absence of musical ear syndrome by the patient. RESULTS Musical ear syndrome started 1 day after implantation. It ceased immediately after cochlear explantation, but reappeared 3 months later. CONCLUSIONS Several types of factors seem to determine whether a musical ear syndrome is present or not. We propose to differentiate between triggers, modifiers, and conditions, which determine a base vulnerability. Vulnerability seems to be increased by auditory deprivation and by habitual retrieval of music from memory. Cochlear implantation or explantation seems to act as triggers. The proposed framework may help to stimulate reporting of more potentially relevant factors in future case reports on musical ear syndrome, and ultimately to help to understand this condition better