Analytical Bayesian approach for the design of surveillance and control programs to assess pest-eradication success.

Large invasive species eradication programs are undertaken to protect native biodiversity and agriculture. Programs are typically followed by a series of surveys to assess the likelihood of eradication success and, when residual pests are detected, small-scale control or 'mop-ups' are implemented to eliminate these infestations. Further surveys follow to confirm absence with 'freedom' declared when a target probability of absence is reached. Such biosecurity programs comprise many interacting processes - stochastic biological processes including growth, and response and control interventions - and are an important component of post-border biosecurity. Statistical frameworks formulated to contribute to the design and efficiency of these surveillance and control programs are few and, those available, rely on the simulation of the component processes. In this paper we formulate an analytical Bayesian framework for a general biosecurity program with multiple components to assess pest-eradication success. Our model incorporates stochastic growth and detection processes, and several pest control mechanisms. Survey results and economic considerations are also taken into account to support a range of biosecurity management decisions. Using a case study we demonstrate that solutions match published simulation results and extend the available analysis. Principally, we show how analytical solutions can offer a powerful tool to support the design of effective and cost-efficient biosecurity systems, and we establish some general principles that guide and contribute to robust design.

Power on: The rapid transition of a large interdisciplinary behavioral health department to telemental health during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic necessitated a rapid transition to telemental health (TMH) for behavioral health services in the behavioral health department of a large integrated primary care organization. Although the COVID-19 pandemic was the initial trigger for rapid organizational change, systems were developed with a focus on longer term scalability and sustainability. METHODS: This paper discusses the process of organizational change within our healthcare delivery system using the Strengths, Opportunities, Aspirations, and Results (SOAR) framework. Within this framework a structured mixed methods survey of 38 clinicians representing 5 different disciplines was conducted. Internal and survey data were analyzed to evaluate and guide the iterative change process. RESULTS: The majority of BH clinicians reported that they were as or more effective with TMH. The transition to TMH in our organization resulted in increased access to care, with a 10.3% increase in BH visit completions. The transition to TMH may benefit clinician work-life balance, but requires resources to support clinical, technological, and communication/teamwork changes. IMPLICATIONS/CONCLUSIONS: TMH is a feasible treatment modality for integrated care settings. It is cost-effective and well-accepted by clinicians. The SOAR framework can be used to guide rapid organizational change and ongoing QI processes.

Analytical Bayesian models to quantify pest eradication success or species absence using zero-sighting records.

It is not possible to establish the absence of a population with certainty using imperfect zero-sighting records, but absence can be inferred. In this paper we use Bayesian methods to formulate analytical inferred distributions and statistics. When such formulations are available, they offer a highly efficient and powerful means of analysis. Our purpose is to provide accessible and versatile formulations to support an assessment of population absence for management decisions, using data from a series of regular and targeted surveys with zero-sightings. The stochastic processes considered here are prior population size, growth and imperfect detection, which are combined into a single distribution with sufficient flexibility to accommodate alternative distributions for each of the driving processes. Analytical solutions formulated include the inferred mean and variance for population size or number of infested survey-units, the probability of absence, the probability of a series of negative surveys conditional on presence, and the probability a population is first detected in a given survey, although we also formulate other statistics and provide explicit thresholds designed to support management decisions. Our formulation and results are straightforward to apply and provide insight into the nonlinear interactions and general characteristics of such systems. Although motivated by an assessment of population absence following a pest eradication program, results are also relevant to the status of threatened species, to 'proof-of-freedom' requirements for trade, and for inferring population size when a population is first detected.

Dead clades walking are a pervasive macroevolutionary pattern.

D. Jablonski [Proc. Natl. Acad. Sci. U.S.A. 99, 8139-8144 (2002)] coined the term "dead clades walking" (DCWs) to describe marine fossil orders that experience significant drops in genus richness during mass extinction events and never rediversify to previous levels. This phenomenon is generally interpreted as further evidence that the macroevolutionary consequences of mass extinctions can continue well past the formal boundary. It is unclear, however, exactly how long DCWs are expected to persist after extinction events and to what degree they impact broader trends in Phanerozoic biodiversity. Here we analyze the fossil occurrences of 134 skeletonized marine invertebrate orders in the Paleobiology Database (paleobiodb.org) using a Bayesian method to identify significant change points in genus richness. Our analysis identifies 70 orders that experience major diversity losses without recovery. Most of these taxa, however, do not fit the popular conception of DCWs as clades that narrowly survive a mass extinction event and linger for only a few stages before succumbing to extinction. The median postdrop duration of these DCW orders is long (>30 Myr), suggesting that previous studies may have underestimated the long-term taxonomic impact of mass extinction events. More importantly, many drops in diversity without recovery are not associated with mass extinction events and occur during background extinction stages. The prevalence of DCW orders throughout both mass and background extinction intervals and across phyla (>50% of all marine invertebrate orders) suggests that the DCW pattern is a major component of macroevolutionary turnover.

Modelling the impact of biosecurity practices on the risk of high pathogenic avian influenza outbreaks in Australian commercial chicken farms.

As of 2018, Australia has experienced seven outbreaks of highly pathogenic avian influenza (HPAI) in poultry since 1976, all of which involved chickens. There is concern that increases in free-range farming could heighten HPAI outbreak risk due to the potential for greater contact between chickens and wild birds that are known to carry low pathogenic avian influenza (LPAI). We use mathematical models to assess the effect of a shift to free-range farming on the risk of HPAI outbreaks of H5 or H7 in the Australian commercial chicken industry, and the potential for intervention strategies to reduce this risk. We find that a shift of 25% of conventional indoor farms to free-range farming practices would result in a 6-7% increase in the risk of a HPAI outbreak. Current practices to treat water are highly effective, reducing the risk of outbreaks by 25-28% compared to no water treatment. Halving wild bird presence in feed storage areas could reduce risk by 16-19% while halving wild bird access of potential bridge-species to sheds could reduce outbreak risk by 23-25%, and relatively small improvements in biosecurity measures could entirely compensate for increased risks due to the increasing proportion of free-range farms in the industry. The short production cycle and cleaning practices for chicken meat sheds considerably reduce the risk that an introduced low pathogenic avian influenza virus is maintained in the flock until it is detected as HPAI through increased mortality of chickens. These findings help explain HPAI outbreak history in Australia and suggest practical changes in biosecurity practices that could reduce the risk of future outbreaks.

Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification.

Background: Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis. Patients and methods: We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients' outcomes. Results: Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016). Conclusions: Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.

Metrology for the next generation of semiconductor devices.

The semiconductor industry continues to produce ever smaller devices that are ever more complex in shape and contain ever more types of materials. The ultimate sizes and functionality of these new devices will be affected by fundamental and engineering limits such as heat dissipation, carrier mobility and fault tolerance thresholds. At present, it is unclear which are the best measurement methods needed to evaluate the nanometre-scale features of such devices and how the fundamental limits will affect the required metrology. Here, we review state-of-the-art dimensional metrology methods for integrated circuits, considering the advantages, limitations and potential improvements of the various approaches. We describe how integrated circuit device design and industry requirements will affect lithography options and consequently metrology requirements. We also discuss potentially powerful emerging technologies and highlight measurement problems that at present have no obvious solution.

The influence of androgens on hibernation phenology of free-living male arctic ground squirrels.

Free-living ground squirrel species are sexually dimorphic in hibernation phenology. The underlying causes of these differences are not yet known. Androgens, testosterone (T) in particular, inhibit hibernation. To determine the influence of endogenous androgens on annual timing of hibernation we first measured circulating levels of T and dehydroepiandrosterone (DHEA), an adrenal androgen implicated in non-mating season aggression in other species, in free-living male arctic ground squirrels (Urocitellus parryii, AGS). We also manipulated endogenous androgen levels by surgical castration, and consequently compared body temperature records from intact (n=24) and castrated (n=9) males to elucidate the influence of endogenous androgens on annual body temperature cycles. The highest T levels (0.53±0.10ng/mL) were in reproductively mature male AGS in spring; whereas, both immature males in spring and all males in late summer had T levels an order of magnitude lower (0.07±0.01 and 0.06±0.00ng/mL, respectively). DHEA levels were higher in males during the late summer compared to reproductively mature males in spring (120.6±18.9 and 35.9±2.3pg/mL, respectively). Eliminating gonadal androgens via castration resulted in males delaying euthermy by extending heterothermy significantly in spring (Apr 22 ±2.9) than reproductive males (Mar 28 ±3.9) but did not change the timing of hibernation onset (castrate: Oct 12 ±1.0 vs. intact: Oct 3 ±3.1). We conclude that while androgens play a significant role in spring hibernation phenology of males, their role in fall hibernation onset is unclear.

Enabling Quantitative Optical Imaging for In-die-capable Critical Dimension Targets.

Dimensional scaling trends will eventually bring semiconductor critical dimensions (CDs) down to only a few atoms in width. New optical techniques are required to address the measurement and variability for these CDs using sufficiently small in-die metrology targets. Recently, Qin et al. [Light Sci Appl, 5, e16038 (2016)] demonstrated quantitative model-based measurements of finite sets of lines with features as small as 16 nm using 450 nm wavelength light. This paper uses simulation studies, augmented with experiments at 193 nm wavelength, to adapt and optimize the finite sets of features that work as in-die-capable metrology targets with minimal increases in parametric uncertainty. A finite element based solver for time-harmonic Maxwell's equations yields two- and three-dimensional simulations of the electromagnetic scattering for optimizing the design of such targets as functions of reduced line lengths, fewer number of lines, fewer focal positions, smaller critical dimensions, and shorter illumination wavelength. Metrology targets that exceeded performance requirements are as short as 3 µm for 193 nm light, feature as few as eight lines, and are extensible to sub-10 nm CDs. Target areas measured at 193 nm can be fifteen times smaller in area than current state-of-the-art scatterometry targets described in the literature. This new methodology is demonstrated to be a promising alternative for optical model-based in-die CD metrology.

Thermogenic capacity at subzero temperatures: how low can a hibernator go?

Abstract Hibernation in mammals is a physiological and behavioral adaptation to survive intervals of low resource availability through profound decreases in metabolic rate (MR), core body temperature (Tb), and activity. Most small mammalian hibernators thermoconform, with Tb approximating ambient temperature (Ta); arctic species are an exception, since they must actively defend what can be large thermal gradients between Tb and Ta. Here we compare the thermogenic capacity of the arctic ground squirrel (Urocitellus parryii) to that of the golden-mantled ground squirrel (Callospermophilus lateralis), a temperate-zone montane hibernator. We allowed animals to reenter torpor at sequentially lower Ta's and found that arctic ground squirrels maintained steady state torpor at Ta's as low as -26°C, through a 36-fold increase in torpid MR (TMR), compared to their minimum TMR, exhibited at a Ta of 0°C. Golden-mantled ground squirrels are able to maintain steady state torpor at Ta's at least as low as -8°C, through a 13.5-fold increase in MR, compared to their minimum TMR at a Ta of 2°C. In a second experiment, torpid animals were exposed to continuously decreasing Ta's (0.25°C/30 min); individuals of both species increased their metabolism while remaining torpid at low Ta's (as low as -30°C for arctic ground squirrels and -10°C for golden-mantled ground squirrels). Although the capacity to hibernate at subfreezing Ta's is not unique to arctic ground squirrels, their large body size, greater torpid metabolic scope, and previously ascribed capacity to supercool allow them to occupy much colder hibernacula for prolonged seasons of hibernation.

Using behavior change to reduce child lead exposure in resource-poor settings: a formative study.

The objective of this formative research was to explore the acceptability and feasibility of changing housekeeping behaviors as a low-cost approach that may reduce childhood lead exposure in Johannesburg, South Africa. Using the Trials of Improved Practices (TIPs) methodology, modified housekeeping behaviors were negotiated with participants who chose the behaviors they wanted to try and then performed them in their homes over 4 weeks. Researchers interviewed them at the end of the month to understand their experience of trying out the behaviors. The modified behaviors offered to each participant were as follows: cleaning window sills with detergent and water, cleaning window sills more frequently, mopping floors with two buckets (one with soapy water for washing and one with clean water for rinsing), mopping floors more frequently, dusting surfaces with detergent and water and dusting surfaces more frequently. Participants found cleaning window sills with soap and water and cleaning them more often the most acceptable and feasible of behavior modifications. Environmental samples showed a significant reduction in lead dust on window sills. These findings can assist in the development of acceptable and feasible medium-term interventions to reduce childhood lead exposure in resource-poor settings until more robust health policies are implemented.

Temporal and spatial mapping of red grouper Epinephelus morio sound production.

The goals of this project were to determine the daily, seasonal and spatial patterns of red grouper Epinephelus morio sound production on the West Florida Shelf (WFS) using passive acoustics. An 11 month time series of acoustic data from fixed recorders deployed at a known E. morio aggregation site showed that E. morio produce sounds throughout the day and during all months of the year. Increased calling (number of files containing E. morio sound) was correlated to sunrise and sunset, and peaked in late summer (July and August) and early winter (November and December). Due to the ubiquitous production of sound, large-scale spatial mapping across the WFS of E. morio sound production was feasible using recordings from shorter duration-fixed location recorders and autonomous underwater vehicles (AUVs). Epinephelus morio were primarily recorded in waters 15-93 m deep, with increased sound production detected in hard bottom areas and within the Steamboat Lumps Marine Protected Area (Steamboat Lumps). AUV tracks through Steamboat Lumps, an offshore marine reserve where E. morio hole excavations have been previously mapped, showed that hydrophone-integrated AUVs could accurately map the location of soniferous fish over spatial scales of <1 km. The results show that passive acoustics is an effective, non-invasive tool to map the distribution of this species over large spatial scales.

Electroencephalographic sleep elements and outcome in acute encephalopathic patients: a 4-year cohort study.

BACKGROUND AND PURPOSE: Acute encephalopathy in hospitalized patients is common and associated with high mortality. Preservation of physiological sleep has been associated with favorable outcomes in acute brain injury. It is hypothesized that electroencephalographic presence of sleep elements is associated with good outcome in encephalopathic adults. METHODS: This observational study was performed at an academic tertiary medical care center. Clinical data, electroencephalogram (EEG) characteristics and outcome of critically ill patients with acute encephalopathy were assessed. EEGs were interpreted regarding the presence of sleep elements (K-complexes, vertex sharp-waves and sleep spindles). Associations between sleep elements and outcome (graded by the Glasgow Outcome Scale, GOS) were analyzed. RESULTS: One hundred and forty-two consecutive patients with a median age of 64.5 years (range 18-98) and mean Glasgow Coma Scale 10.4 (± 3.8) were included. Leading etiologies were infections (47.2%), intracranial hemorrhages (14.1%) and ischaemic strokes (10.6%). All EEGs demonstrated encephalopathy patterns and 38% had ≥ 1 sleep element (27.5% K-complexes, 31.7% vertex sharp-waves and 33.8% sleep spindles). Patients without sleep elements were older (P = 0.010) and septic shock was more common (P = 0.014). Amongst sleep elements, K-complexes were significantly associated with good outcome, even after adjusting for possible confounders (odds ratio for GOS 5 = 2.79, 95% confidence interval 1.16-6.69) and without significant effect modification across subgroups. CONCLUSIONS: Whilst EEG sleep elements were detected more frequently in patients with favorable outcome, only K-complexes were significantly and independently associated with good outcome in intensive care unit patients with acute encephalopathy, findings that need to be confirmed in larger prospective studies.

[Nationwide statements from regional data: methods of the Center for Cancer Registry Data]. / Von regionalen Daten zu bundesweiten Aussagen : Die Methoden im Zentrum für Krebsregisterdaten.

Despite having achieved nationwide registry coverage in addition to substantial improvements in data on the epidemiology of cancer in Germany, the Centre for Cancer Registry Data continues to estimate national statistics on incidence, survival, and prevalence instead of calculating these directly from available data. The methods used for evaluations are based initially on estimates of registration completeness or, for survival analyses, an assessment of the quality of follow-up data. The completeness of incident case registration is estimated on the basis of the mortality/incidence procedure, which assumes a largely constant relationship between the mortality and incidence of a cancer type among people of the same age and sex across federal states. Inclusion criteria for consideration of registry data in national survival analyses are less than 15% of death certificate only (DCO) cases and plausible survival for patients with pancreatic cancer or metastatic lung cancer. Of the 477,300 incident cancer cases estimated for 2010, 429,900 were reported by the cancer registries (90%), and ten federal states contributed data to national survival estimates.

Deletion of Irf5 protects hematopoietic stem cells from DNA damage-induced apoptosis and suppresses γ-irradiation-induced thymic lymphomagenesis.

Repeated low-dose γ-irradiation (IR) induces thymic lymphoma in mice because of oncogenic mutations propagating from a primitive hematopoietic stem/progenitor cell (HSC) in the bone marrow. It is well known that IR-induced thymic lymphomagenesis is markedly enhanced by p53 deficiency, yet data also indicate that p53-dependent apoptosis can actively drive tumor formation in this model. The latter was recently expounded on by findings from Puma-deficient mice, indicating that loss of this proapoptotic p53 target gene results in protection from IR-induced lymphomagenesis rather than enhanced susceptibility to. Similar to Puma, the transcription factor interferon regulatory factor 5 (Irf5) has been reported as a p53 target gene and is required for DNA damage-induced apoptosis. To date, no studies have been performed to elucidate the in vivo role of IRF5 in tumorigenesis. Given its essential role in DNA damage-induced apoptosis, we explored the tumor suppressor function of IRF5 in IR-induced thymic lymphomagenesis. Somewhat surprisingly, we found that thymic lymphoma development was significantly suppressed in Irf5(-/-) mice as compared with wild-type littermates. Suppression was due, in part, to reduced thymocyte and HSC apoptosis, resulting in reduced compensatory proliferation, and reduced replication stress-associated DNA damage. The observed effects were independent of p53 or Puma as these proteins were upregulated in Irf5(-/-) mice in response to IR. This study demonstrates an important new role for IRF5 in maintaining HSC homeostasis after IR and supports the non-redundant functions of IRF5, p53 and PUMA in DNA damage-induced lymphomagenesis. We propose that IRF5 may be an attractive target for developing therapeutic agents to ameliorate radiation-induced bone marrow injury.

Changes in cancer incidence attributable to tobacco smoking in Germany, 1999-2008.

Tobacco smoking, a major cancer risk factor, is very common in Germany as in many other high-income countries. Few studies have assessed the burden of tobacco-associated cancer incidence in the German population. We calculated the proportion of cancers attributable to tobacco smoking to estimate the burden of tobacco-associated cancer in 1999 and 2008. Smoking prevalence was determined from national surveys of a representative sample of the German population in 1998 and 2008-2011, and data on relative risks were obtained from meta-analyses. Cancer incidence for the years 1999 and 2008 was estimated by the German Centre for Cancer Registry Data at the Robert Koch Institute. We estimate that 72,208 incident cancer cases were attributable to tobacco smoking in Germany in 2008, an increase of >6,200 cases over 1999 levels. Among the cases in 2008 were 55,057 cases among men (22.8% (95% CI, 21.3-24.1) of all new cases) and 17,151 cases among women (7.9% (95% CI, 7.21-8.68) of all new cases). The highest proportions attributable to smoking were estimated for cancer of the lung, larynx, pharynx and the lower urinary tract. Tobacco smoking is currently responsible for more than one in five cancer cases among men and nearly 1 in 12 among women. Considering the increasing trends in cancer incidence and, until very recently, rising prevalence of smoking among women, it can be expected that the number of tobacco-attributable cancer cases will rise further.

[Data quality or differences in oncological care? - standards of reporting for cancer survival analyses based on registry data]. / Datenqualität oder Unterschiede in der onkologischen Versorgung? - Berichtsstandards für Überlebenszeitanalysen mit Krebsregisterdaten.

BACKGROUND: The results of population-based cancer survival analyses are essential criteria with regard to the evaluation of oncological care. Their use and their interpretation as such require knowledge and transparency with regard to the data basis in order to avoid inadequate conclusions. METHOD: The working group 'survival analysis' of the Association of Population-Based Cancer Registries in Germany (GEKID) has identified factors within cancer registration and data evaluation which may distort population-based cancer survival analyses to a relevant degree. Recommendations in terms of standards of reporting were developed by mutual consent following empirical studies and discussions within GEKID. RESULTS: We provide a list of 17 indicators to be taken into account and to be presented within the scope of population-based survival analyses. CONCLUSIONS: Referring to the "standards of reporting concerning population-based cancer survival analyses" introduced by GEKID there is a proposal on data transparency on hand, which might contribute substantially to the assessability of outcome quality in oncological care.

[The (German) Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI) in Berlin]. / Das Zentrum für Krebsregisterdaten (ZfKD) im Robert Koch-Institut (RKI) in Berlin.

Cancer represents the second most common cause of death in Germany. The country's federal states operate regional population-based cancer registries that collect and analyze data on cancer patients. This provides an essential basis for describing the cancer burden in the German population. In order to obtain valid and reliable information on cancer incidence at the national level, the Robert Koch Institute (RKI) set up the Federal Cancer Surveillance Unit in 1983 as a central institution for evaluating this cancer registry data. In August 2009, when the Federal Cancer Registry Data Act (BKRG) came into force, the Center for Cancer Registry Data (ZfKD) at the RKI took over the work of the Cancer Surveillance Unit with a broader remit. In the future, it will also regularly publish findings on survival, prevalence, and tumor stage distribution. A newly established record linkage process will help identify multiple submissions from the federal states. Further innovations and new tasks of the ZfKD include expanding an interactive Internet platform and encouraging a more intensive use of cancer registry data for epidemiological research by providing datasets to external scientists. The range of information available to the interested public is also to be expanded.