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.

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.

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.

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.

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.

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.

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.

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.

[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.

[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.

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.

[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.

Rejection of first-set skin allografts in man. the microvasculature is the critical target of the immune response.

Recent reports of microvascular injury in delayed hypersensitivity skin reactions prompted us to reexamine the pathogenesis of first-set skin allograft rejection in man using morphologic techniques that allowed both extensive vessel sampling and unequivocal evaluation of microvascular endothelium. We here report that widespread microvascular damage is a characteristic, early consequence of the cellular immune response to first-set human skin allografts and is qualitatively similar to, but substantially more extensive than, that occurring in delayed hypersensitivity reactions. Microvascular damage in invariably preceded significant epithelial necrosis and affected initially and primarily those venules, arterioles, and small veins enveloped by lymphocytes. Vessels of both the allograft itself and the underlying graft bed (recipient tissue) were equally affected. These data suggest that endothelial cells of the microvasculature are the critical target of the immune response in first-set vascularized skin allograft rejection in man and that rejection can be attributed largely to ischemic infarction resulting from extensive microvascular damage. Other mechanisms, such as direct cellular contacts between infiltrating lymphocytes and epithelium, apparently played only a minor role. The findings presented here indicate that the rejection of first-set vascularized skin allografts, though induced by immunologically specific mechanisms, is primarily effected by final pathways that are relatively nonspecific and that may cause damage to both foreign and host vessels and cells. Rather than contradicting studies demonstrating the exquisite specificity of allograft rejection in other systems, these findings provide a further example of the heterogeneity of the cellular immune response. Recognition of the critical role of immunologically mediated microvascular injury may prove important both for an understanding of the biology of allograft rejection and for strategies aimed at prolonging allograft survival.

Deep supercooling, vitrification and limited survival to -100{degrees}C in the Alaskan beetle Cucujus clavipes puniceus (Coleoptera: Cucujidae) larvae.

Larvae of the freeze-avoiding beetle Cucujus clavipes puniceus (Coleoptera: Cucujidae) in Alaska have mean supercooling points in winter of -35 to -42 degrees C, with the lowest supercooling point recorded for an individual of -58 degrees C. We previously noted that some larvae did not freeze when cooled to -80 degrees C, and we speculated that these larvae vitrified. Here we present evidence through differential scanning calorimetry that C. c. puniceus larvae transition into a glass-like state at temperatures<-58 degrees C and can avoid freezing to at least -150 degrees C. This novel finding adds vitrification to the list of insect overwintering strategies. While overwintering beneath the bark of fallen trees, C. c. puniceus larvae may experience low ambient temperatures of around -40 degrees C (and lower) when microhabitat is un-insulated because of low snow cover. Decreasing temperatures in winter are correlated with loss of body water from summer high levels near 2.0 to winter lows near 0.4 mg mg(-1) dry mass and concomitant increases in glycerol concentrations (4-6 mol l(-1)) and thermal hysteresis. Finally, we provide direct evidence that Cucujus from Wiseman, Alaska, survive temperatures to -100 degrees C.

Freeze avoidance in a mammal: body temperatures below 0 degree C in an Arctic hibernator.

Hibernating arctic ground squirrels, Spermophilus parryii, were able to adopt and spontaneously arouse from core body temperatures as low as -2.9 degrees C without freezing. Abdominal body temperatures of ground squirrels hibernating in outdoor burrows were recorded with temperature-sensitive radiotransmitter implants. Body temperatures and soil temperatures at hibernaculum depth reached average minima during February of -1.9 degrees and -6 degrees C, respectively. Laboratory-housed ground squirrels hibernating in ambient temperatures of -4.3 degrees C maintained above 0 degree C thoracic temperatures but decreased colonic temperatures to as low as -1.3 degrees C. Plasma sampled from animals with below 0 degree C body temperatures had normal solute concentrations and showed no evidence of containing antifreeze molecules.

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.

Benign transient hyperphosphatasemia associated with Epstein-Barr virus enteritis in a pediatric liver transplant patient: a case report.

Transient hyperphosphatasemia was found in a 3-year-old male liver transplant recipient. The condition was associated with diarrheal disease due to the Epstein-Barr virus (EBV). Immunosuppression was tapered and valganciclovir prescribed for 3 months, after which the diarrhea resolved and the EBV polymerase chain reaction assays became negative. After 6 months, alkaline phosphatase levels normalized. Isolated elevation of alkaline phosphatase in conjunction with enteric infection is a rare condition. No further diagnostic or therapeutic interventions except treatment of the underlying infection are needed, as this has been shown to be a benign, transient condition.

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.

mRNA stability and polysome loss in hibernating Arctic ground squirrels (Spermophilus parryii).

All small mammalian hibernators periodically rewarm from torpor to high, euthermic body temperatures for brief intervals throughout the hibernating season. The functional significance of these arousal episodes is unknown, but one suggestion is that rewarming may be related to replacement of gene products lost during torpor due to degradation of mRNA. To assess the stability of mRNA as a function of the hibernation state, we examined the poly(A) tail lengths of liver mRNA from arctic ground squirrels sacrificed during four hibernation states (early and late during a torpor bout and early and late following arousal from torpor) and from active ground squirrels sacrificed in the summer. Poly(A) tail lengths were not altered during torpor, suggesting either that mRNA is stabilized or that transcription continues during torpor. In mRNA isolated from torpid ground squirrels, we observed a pattern of 12 poly(A) residues at greater densities approximately every 27 nucleotides along the poly(A) tail, which is a pattern consistent with binding of poly(A)-binding protein. The intensity of this pattern was significantly reduced following arousal from torpor and undetectable in mRNA obtained from summer ground squirrels. Analyses of polysome profiles revealed a significant reduction in polyribosomes in torpid animals, indicating that translation is depressed during torpor.