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A common basis to address the dynamics of directly transmitted infectious diseases, such as COVID-19, are compartmental (or SIR) models. SIR models typically assume homogenous population mixing, a simplification that is convenient but unrealistic. Here we validate an existing model of a scale-free fractal infection process using high-resolution data on COVID-19 spread in São Caetano, Brazil. We find that transmission can be described by a network in which each infectious individual has a small number of susceptible contacts, of the order of 2-5. This model parameter correlated tightly with physical distancing measured by mobile phone data, such that in periods of greater distancing the model recovered a lower average number of contacts, and vice versa. We show that the SIR model is a special case of our scale-free fractal process model in which the parameter that reflects population structure is set at unity, indicating homogeneous mixing. Our more general framework better explained the dynamics of COVID-19 in São Caetano, used fewer parameters than a standard SIR model and accounted for geographically localized clusters of disease. Our model requires further validation in other locations and with other directly transmitted infectious agents., (© 2023 Published by Elsevier Inc.)

In the present work we investigate the growth of monolayer MoSe 2 on selenium-intercalated graphene on Ru(0001), a model layered heterostructure combining a transition metal dichalcogenide with graphene, using low energy electron microscopy and micro-diffraction. Real-time observation of MoSe 2 on graphene growth reveals the island nucleation dynamics at the nanoscale. Upon annealing, larger islands are formed by sliding and attachment of multiple nanometer-sized MoSe 2 flakes. Local micro-spot angle-resolved photoemission spectroscopy reveals the electronic structure of the heterostructure, indicating that no charge transfer occurs within adjacent layers. The observed behavior is attributed to intercalation of Se at the graphene/Ru(0001) interface. The unperturbed nature of the proposed heterostructure therefore renders it as a model system for investigations of graphene supported TMD nanostructures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013., Methods: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses., Findings: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins., Interpretation: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings., Funding: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis and may have affected healthcare-associated infection (HAI) prevention strategies. We evaluated the impact of the COVID-19 pandemic on HAI incidence in Brazilian intensive care units (ICUs)., Methods: In this ecological study, we compared adult patients admitted to the ICU from April through June 2020 (pandemic period) with the same period in 2019 (prepandemic period) in 21 Brazilian hospitals. We used the Wilcoxon signed rank-sum test in a pairwise analysis to compare the following differences between the pandemic and the prepandemic periods: microbiologically confirmed central-line-associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) incidence density (cases per 1,000 central line and ventilator days, respectively), the proportion of organisms that caused HAI, and antibiotic consumption (DDD)., Results: We detected a significant increase in median CLABSI incidence during the pandemic: 1.60 (IQR, 0.44-4.20) vs 2.81 (IQR, 1.35-6.89) ( P = .002). We did not detect a significant difference in VAP incidence between the 2 periods. In addition, we detected a significant increase in the proportion of CLABSI caused by Enterococcus faecalis and Candida spp during the pandemic, although only the latter retained statistical significance after correction for multiple comparisons. We did not detect a significant change in ceftriaxone, piperacillin-tazobactam, meropenem, or vancomycin consumption between the studied periods., Conclusions: There was an increase in CLABSI incidence in Brazilian ICUs during the first months of COVID-19 pandemic. Additionally, we detected an increase in the proportion of CLABSI caused by E. faecalis and Candida spp during this period. CLABSI prevention strategies must be reinforced in ICUs during the COVID-19 pandemic.

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.

The southern green stink bug (SGSB) Nezara viridula L. is one of the most common stink bug species in the United States and can cause significant yield loss in a variety of crops. A suitable marker for the assessment of gene-editing tools in SGSB has yet to be characterized. The white gene, first documented in Drosophila, has been a useful target to assess the efficiency of introduced mutations in many species as it controls pigmentation processes and mutants display readily identifiable phenotypes. In this study we used the RNAi technique to investigate functions and phenotypes associated with the white ortholog in the SGSB and to validate white as a marker for genetic transformation in this species. This study revealed that white may be a suitable marker for germline transformation in the SGSB as white transcript knockdown was not lethal, did not impair embryo development and provided a distinguishable phenotype. Our results demonstrated that the white ortholog in SGSB is involved in the pathway for ommochrome synthesis and suggested additional functions of this gene such as in the integument composition, management of hemolymph compounds and riboflavin mobilization., (© 2022. The Author(s).)

The objectives of this study were to investigate how milk replacer (MR) allowance and differing concentrations of starch and neutral detergent fiber in starter alters visceral tissue and overall growth of the calf. Calves were randomly assigned to 1 of 4 dietary treatments (n = 12 per treatment) arranged in a 2 × 2 factorial based on daily MR allowance (MRA) and amount of starch in pelleted starter (SPS) as follows: 0.691 kg of MR/d [dry matter (DM) basis] with starter containing low or high starch (12.0% and 35.6% starch, respectively) and 1.382 kg of MR/day (DM) with starter containing low or high starch. All calves were housed in individual pens with straw bedding until wk 5 when bedding was covered to minimize intake. Calves were fed MR twice daily (0700 and 1700 h) containing 24.5% crude protein (DM) and 19.8% fat (DM), and had access to pelleted starter (increased by 50 g/d if there were no refusals before weaning, and then 200 g/d during and after weaning) and water starting on d 1. Calves arrived between 1 and 3 d of age and were enrolled into an 8-wk study, with calves undergoing step-down weaning during wk 7. Intakes were measured daily, and body weight (BW) and blood samples were recorded and collected weekly. Calves were dissected in wk 8 for visceral tissue measurements. Overall, there was increased MR DM intake for the high- (0.90 ± 0.01 kg/d; ± SE) compared with the low-MRA (0.54 ± 0.01 kg/d) calves, whereas starter DM intake increased in low- (0.47 ± 0.05 kg/d) compared with high-MRA (0.20 ± 0.05 kg/d) calves, which was driven by increases in wk 6, 7, and 8. High-MRA calves had increased BW during wk 2, 3, 4, 5, 6, and 7. The difference in BW disappeared by wk 8, with overall average daily gain having a tendency to be increased in high (0.57 ± 0.04 kg/d) compared with low-MRA (0.50 ± 0.04 kg/d) calves, whereas average daily gain was increased in high-MRA calves during wk 2 and 3 and increased in low-MRA calves during wk 7 and 8. There were several differences throughout visceral tissue measurements, but most notably, an increase in rumen mass (i.e., full, empty, and digesta weights) in low- compared with high-MRA calves, as well as in low- compared with high-SPS calves was observed. The length, width, and 2-dimensional area of rumen papillae were also increased in low- (area: 0.88 ± 0.03 mm 2 ) compared with high-MRA (0.46 ± 0.03 mm 2 ) calves. The majority of differences were attributed to increased MR allowance, which contributed to reduced pelleted starter intake by more than 50% and reduced rumen development, whereas differences in starch intake from the completely pelleted starter had minimal effects on overall growth and tissue measurements., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

We evaluated the seroprevalence of SARS-CoV-2 and risk factors among 4987 oligo/asymptomatic healthcare workers; seroprevalence was 14% and factors associated with SARS-CoV-2 infection were lower educational level (aOR, 1.93; 95% CI, 1.03-3.60), using public transport to work (aOR, 1.65; 95% CI, 1.07-2.62), and working in cleaning or security (aOR, 2.05; 95% CI, 1.04-4.03)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The prophylactic use of oral antimicrobials, such as neomycin, in milk replacer (MR) or whole milk is a common practice in calf-rearing that is thought to aid in preventing disease. Heavy reliance on antimicrobials is of concern not only because of the development of antimicrobial resistance, but also because of the potentially negative effects on health. The objective of this study was to investigate the effects of neomycin on calf health and growth performance. One hundred and sixty calves (approximately 3-10 d of age), distributed across 2 experimental periods, were stratified by body weight (BW) and serum total protein, and assigned to 1 of 3 treatments: control (CON; nonmedicated MR, n = 60), short-term antibiotic (ST; neomycin mixed in MR from d 1-14, n = 50), or long-term antibiotic (LT; neomycin in ​MR from d 1-28, n = 50). Arrival BW (47.69 ± 0.87 kg) and serum total protein (5.67 ± 0.09 g/dL) were not different between treatment groups. Neomycin in ST and LT was dosed in MR at a rate of 20 mg/kg of BW and was adjusted weekly according to BW. Calf BW was measured weekly for 49 d, and health indicators (fecal score, attitude score, respiratory score, and rectal temperature), MR intake, starter intake, and the use of additional electrolytes and antimicrobials were recorded daily. Calves in the CON group experienced a higher proportion of days with diarrhea (20.32 ± 0.02%) compared with ST (14.70 ± 0.02%) or LT (13.80 ± 0.02%) calves, as well as longer bouts of diarrhea (7.45 ± 0.38 d, 5.69 ± 0.46 d, and 5.62 ± 0.45 d for CON, ST, and LT calves, respectively). Calves in the CON group also experienced higher fecal scores (score of 0.64 ± 0.04) than ST (score of 0.53 ± 0.04) or LT (score of 0.49 ± 0.04) calves, especially at d 7. However, no differences were observed in other health-related measures. The time to reach first diarrhea and first respiratory illness was not different between treatments, nor was the time to recover from respiratory illness. The time to intervention with additional electrolytes or antimicrobials was not different between treatment groups. Furthermore, growth performance, feed intake, and feed conversion ratio were not different. No differences were found when comparing ST and LT, except in the defined daily dose of total antimicrobials received. Calves in the LT group received a higher overall dose than ST calves, and both ST and LT calves received a higher dose than CON calves, which received no prophylactic antimicrobials. Given that there were no differences in performance variables and no additional health benefits aside from reduced fecal scores in calves fed neomycin, current practices involving the use of antimicrobials on dairy and veal operations need to be considered more prudently., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: We evaluated the performance of a nucleoprotein-based enzyme-linked immunosorbent assay (ELISA) for detection of IgG antibodies to SARS-CoV-2., Methods: The ELISA was based on serum IgG reactivity to a 46-kDa protein derived from the recombinant SARS-CoV2 nucleoprotein. Assay sensitivity was assessed using serum samples from 134 COVID-19 confirmed cases obtained > 15 days after symptom onset. Specificity was determined by testing sera from 94 healthy controls. Cross-reactivity was evaluated with sera from 96 individuals with previous dengue or zika virus-confirmed infections, with 44 sera from individuals with confirmed infections to other respiratory viruses or with bacterial and fungal infections that cause pneumonia and with 40 sera negative for SARS-CoV-2 nucleoprotein by commercial ELISA kits., Results: The majority of subjects were male and ≥ 60 years old. Assay sensitivity was 90.3 % (95 % confidence interval 84.1 %-94.2 %) and specificity was 97.9 % (92.6 %-99.4 %). There was no cross-reactivity with sera from individuals diagnosed with dengue, zika virus, influenza virus, rhinovirus, adenovirus, respiratory syncytial virus, seasonal coronavirus, Mycobacterium tuberculosis, Staphylococcus (S. aureus and coagulase-negative), Streptococcus pneumoniae, Klebsiella pneumoniae and the fungus Aspergillus fumigatus. The level of concordance of our test with results from commercial ELISA kits was 100 %., Conclusion: The nucleoprotein-based ELISA was specific for detection of IgG anti-nucleoprotein antibodies to SARS-CoV-2. It utilizes a frequently employed low expense assay protocol and is easier to perform than other currently available commercial SARS-CoV2 antibody detection tests., (Copyright © 2021. Published by Elsevier B.V.)

Brazil has one of the fastest-growing COVID-19 epidemics worldwide. Non-pharmaceutical interventions (NPIs) have been adopted at the municipal level with asynchronous actions taken across 5,568 municipalities and the Federal District. This paper systematises the fragmented information on NPIs reporting on a novel dataset with survey responses from 4,027 mayors, covering 72.3% of all municipalities in the country. This dataset responds to the urgency to track and share findings on fragmented policies during the COVID-19 pandemic. Quantifying NPIs can help to assess the role of interventions in reducing transmission. We offer spatial and temporal details for a range of measures aimed at implementing social distancing and the dates when these measures were relaxed by local governments.

Formalin-fixed paraffin-embedded (FFPE) tissues are an important source for investigation of dengue virus (DENV) infection, particularly when blood or fresh frozen (FF) samples are unavailable. Histopathologic features and immunohistochemistry may have poor sensitivity and serotype determination is not always possible. Viral RNA genome detection tests are faster and considered the most sensitive technique for this kind of analysis, however, the use of molecular methods applied to FFPE tissues is still limited. The authors applied a single-step multiplex reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for the investigation of DENV infection and typing to FFPE samples of 32 fatal cases received during the 2019 outbreak that occurred in São Paulo state, Brazil. The authors compared the results with those obtained using FF tissues. Of the 24 cases with both FF and FFPE samples, 22 (91.67%) of the FF and 19 (76.20%) of the FFPE specimens were positive. Two cases (8.33%) tested negative in both types of samples. All 8 cases with only FFPE samples available were positive. The accuracy (87.5%) of the RT-qPCR for DENV in FFPE samples were satisfactory. Although the cycle quantification (Cq) values were significantly higher in these materials (P<0.0001, Wilcoxon signed-rank test) when compared with FF tissues, Spearman's rank coefficient indicated a good correlation between the Cq values from both sample types (P=0.0063; rho=0.576). RT-qPCR applied to FFPE samples improved detection of DENV in fatal cases and represents a useful tool for diagnosis and epidemiologic studies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The objective of this cross-sectional study was to evaluate the accuracy of fecal consistency scoring as a measure of fecal dry matter (DM) in dairy calves. This study was conducted at a commercial grain-fed veal facility in southwestern Ontario. A total of 160 calves arrived at the facility in 2 groups of 80 calves each. Calves were fed milk replacer twice daily at 0700 and 1700 h and had ad libitum access from arrival onward to water through nipple drinkers and starter through a shared trough. Fecal consistency scores were evaluated once daily in the first 28 d after arrival before milk feeding. The fecal consistency scoring was conducted using a 4-level scoring scale: 0 = normal (firm but not hard); 1 = soft (does not hold form, piles but spreads slightly); 2 = runny (spreads readily); and 3 = watery (liquid consistency, splatters). Fecal samples were collected from all calves via rectal palpation on d 1, 7, 14, and 21 at 0900 h for determination of fecal DM. Mixed repeated measures linear regression models were built to assess the accuracy of fecal consistency scoring in predicting fecal DM. Over 4 selected time points (d 1, 7, 14, and 21) the 160 calves were observed, 382 (61.6%) had a fecal consistency score of 0, 121 (19.5%) had a score of 1, 85 (13.7%) had a score of 2, and 32 (5.2%) had a score of 3. A fecal score of 0 had a fecal DM of 25.1 ± 8.4%, whereas a fecal score of 1 had a DM of 21.8 ± 8.2%. With respect to calves that had a fecal score of 2 or 3, their fecal DM was 16.0 ± 11.1% and 10.7 ± 6.9%, respectively. In evaluating the pairwise comparisons generated in the repeated measures model that controlled for day of sampling, a fecal score of 0 had a 3.2%, 8.1%, and 12.0% higher fecal DM, respectively, when compared with those that had a fecal score of 1, 2, and 3. In addition, calves with a fecal score of 1 had a 5.0% and 8.8% higher fecal DM than calves with a fecal score of 2 and 3, respectively. Finally, calves with a fecal score of 2 had a 3.8% higher fecal DM than those with a fecal score of 3. This study confirms that using observational fecal consistency scoring can accurately predict diarrhea or a decline in fecal DM., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objectives: We evaluated a rapid chromatographic immunoassay (IgG/IgM antibodies) and an ELISA assay to diagnose COVID-19 in patient sat two Brazilian hospitals., Methods: A total of 122 subjects with COVID-19 were included: 106 SARS-COV-2 RT-PCR-positive patients and 16 RT-PCR-negative patients with symptoms and chest computed tomography (CT) consistent with COVID-19. Ninety-six historical blood donation samples were used as controls. Demographic and clinical characteristics were retrieved from electronic records. Sensitivity and specificity were calculated, as were their 95% binomial confidence intervals using the Clopper-Pearson method. All analyses were performed in R version 3.6.3., Results: The sensitivity of the chromatographic immunoassay in all RT-PCR-positive patients, irrespective of the timing of symptom onset, was 85.8% (95% binomial CI 77.7% to 91.9%). This increased with time after symptom onset, and at >14 days was 94.9% (85.9% to 98.9%). The specificity was 100% (96.4% to 100%). 15/16 (94%) RT- PCR-negative cases tested positive. The most frequent comorbidities were hypertension and diabetes mellitus and the most frequent symptoms were fever, cough, and dyspnea. All RT-PCR-negative patients had pneumonia. The most frequent thoracic CT findings were ground glass changes (n = 11, 68%), which were bilateral in 9 (56%) patients, and diffuse reticulonodular infiltrates (n = 5, 31%)., Conclusions: The COVID-19 rapid chromatographic immunoassay evaluated in this study had a high sensitivity and specificity using plasma, particularly after 14 days from symptom onset. ELISA and qualitative rapid chromatographic immunoassays can be used for the diagnosis of RT-PCR-negative patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Regulatory agencies around the world have been using flexible requirements for approval of new drugs, especially for cancer drugs. The US Food and Drug Administration (FDA) is mostly the first agency to approve new drugs worldwide, mainly due to the faster terms of the accelerated pathway and breakthrough therapy designation. Surrogate endpoints and preliminary data (e.g. single-arm and phase 2 studies) are used for these new approvals, however larger effect sizes are expected. We aim to compare FDA Accelerated vs Regular Pathway approvals and Breakthrough therapy designations (BTD) for lung cancer treatments between 2006 and 2018 regarding study design, sample size, outcome measures and effect size. We assessed the FDA database to collect data from studies that formed the basis of approvals of new drugs or indications for lung cancer spanning from 2006 to 2018. We found that accelerated pathway approvals are based on significantly more single-arm studies with small sample sizes and surrogate primary endpoints. However, effect size was not different between the pathways. A large proportion of studies used to support regular pathway approvals also showed these characteristics that are related to low quality and uncertain evidence. Compared to other approvals, BTD were more frequently based on single-arm studies. There was no significant difference in use of surrogate endpoints or sample size. 44% of BTD were based on studies demonstrating large effect sizes, proportionally more than approvals not receiving this designation. In conclusion, based on the indicators of evidence quality we extracted, criteria's for granting accelerated approval and breakthrough therapy designation seen not clear. Faster approvals are in the majority full of uncertainties which should be viewed with caution and the patient have to be communicated to allow shared decision making. Post-marketing validation is essential., Competing Interests: The authors have declared that no competing interests exist.

The adoption of graphene in electronics, optoelectronics, and photonics is hindered by the difficulty in obtaining high-quality material on technologically relevant substrates, over wafer-scale sizes, and with metal contamination levels compatible with industrial requirements. To date, the direct growth of graphene on insulating substrates has proved to be challenging, usually requiring metal-catalysts or yielding defective graphene. In this work, a metal-free approach implemented in commercially available reactors to obtain high-quality monolayer graphene on c-plane sapphire substrates via chemical vapor deposition is demonstrated. Low energy electron diffraction, low energy electron microscopy, and scanning tunneling microscopy measurements identify the Al-rich reconstruction 31 × 31 R ± 9 ° of sapphire to be crucial for obtaining epitaxial graphene. Raman spectroscopy and electrical transport measurements reveal high-quality graphene with mobilities consistently above 2000 cm 2 V -1 s -1 . The process is scaled up to 4 and 6 in. wafers sizes and metal contamination levels are retrieved to be within the limits for back-end-of-line integration. The growth process introduced here establishes a method for the synthesis of wafer-scale graphene films on a technologically viable basis., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with deposition of large amounts of amyloid within the central nervous system. Amyloid accumulates in two compartments: as plaques within the brain parenchyma and in vessel walls of the cerebral microvasculature. The parenchymal plaque amyloid is thought to result in an early onset Alzheimer's disease (AD) dementia, a phenomenon so common amongst people with DS that it could be considered a defining feature of the condition. The amyloid precursor protein ( APP) gene lies on chromosome 21 and its presence in three copies in DS is thought to largely drive the early onset AD. In contrast, intracerebral haemorrhage (ICH), the main clinical consequence of vascular amyloidosis, is a more poorly defined feature of DS. We review recent epidemiological data on stroke (including haemorrhagic stroke) in order to make comparisons with a rare form of familial AD due to duplication (i.e. having three copies) of the APP region on chromosome 21, here called 'dup-APP', which is associated with more frequent and severe ICH. We conclude that although people with DS are at increased risk of ICH, this is less common than in dup-APP, suggesting the presence of mechanisms that act protectively. We review these mechanisms and consider comparative research into DS and dup-APP that may yield further pathophysiological insight.

Chronic obstructive pulmonary disease (COPD) is a non-communicable long-term condition characterised by accelerated lung-function decline and intermittent episodes of respiratory illness called exacerbations. We discuss the current understanding of the role of viruses in these elements of COPD. The burden of acute viral illness in COPD is great and largely unrecognised. Because naturally occurring exacerbations are inherently difficult to study, only recently have we understood underlying pathophysiological mechanisms and the true prevalence of viral exacerbations. Data are also emerging to support a potential role for chronic viral infection in the progression of stable COPD. As knowledge in these two areas develops, it is clear that the role of viruses in COPD represents a significant unmet clinical need.

Recently, specimens of a Periplaneta sp. were discovered in New York, NY, that did not match the typical morphology of Periplaneta americana L., the ubiquitous American cockroach. Here, we used DNA barcoding and morphological identification to confirm that this newly invasive pest species was indeed Periplaneta japonica Karny, 1908. We discuss this recent invasion in light of known life history traits of this species, with specific predictions for its impact in the urban northeastern United States.

Objective: To assess the occurrence of spontaneous abortion, comparing two different data sources. To estimate the rate of spontaneous abortion over a 2-year period, and examine potential predictors of the risk for incident spontaneous abortion., Methods: We used interview data from a population-based prospective cohort study comprising 11,088 women and data from a linkage of the cohort with the Hospital Discharge Register to compare spontaneous abortions as reported in the interview with those identified in the register. Based on interview data, we estimated the rate of spontaneous abortion during the two-year follow-up. Finally, risk determinants for incident spontaneous abortion were analyzed by means of logistic regression., Results: A total of 654 spontaneous abortions before enrolment in the study were reported by the women compared to 531 abortions found in the register. More than 80% of the spontaneous abortions identified from both sources were recorded in the same year. During follow-up a total of 20.9% of pregnancies intended to be carried to term ended as a spontaneous abortion. In the risk factor analysis, we found that previous spontaneous abortion, being single, never having used oral contraceptives, and use of intrauterine device were associated with increased risk of subsequent spontaneous abortion. In addition, it was indicated that a short interpregnancy interval following a spontaneous abortion may confer an increased risk of abortion in the subsequent pregnancy., Conclusion: We found a high rate of spontaneous abortion in the present study and an acceptable agreement between information obtained by interview and register information. More than 25% of the spontaneous abortions were only reported by the women, and this could not be explained by erroneously reported induced abortions, and may be early, nonhospitalized abortions. We confirm that number of previous spontaneous abortions is a strong determinant, and our data may also indicate a role of previous contraceptive habits. A role of the length of interpregnancy interval in the risk of spontaneous abortion cannot be ruled out.

Background: Few studies have examined smoking prior to pregnancy and the occurrence of spontaneous abortion, as most studies have addressed the risk of spontaneous abortion in relation to smoking during pregnancy. However, results are not entirely consistent. The aim of the present study was to assess the risk of spontaneous abortion considering smoking prior to pregnancy., Methods: We performed a nested case-control study using prospective data from a population-based cohort comprising 11,088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n=343) or who gave birth (n=1,578) during follow-up were selected. Associations between self-reported smoking at enrollment and subsequent spontaneous abortion were analyzed by means of multiple logistic regression., Results: The risk of spontaneous abortion in relation to pre-pregnancy smoking showed a clear dose-response effect. The adjusted odds ratio (95% confidence interval) for spontaneous abortion among current smokers prior to conception was 1.20 (1.04-1.39) per every extra five cigarettes smoked per day. The increased risk was only present for current smokers. The duration of smoking prior to pregnancy was not a significant predictor for subsequent spontaneous abortion., Conclusions: The amount of daily smoking prior to pregnancy seems to be associated with an increased risk of spontaneous abortion, whereas the duration of smoking does not seem to be related to an increased risk of spontaneous abortion.

The stolonal mat is an anatomical feature correlated with increased colonial integration in several lineages of the cnidarian class Hydrozoa. Cnox-2 is a Hox gene known to be expressed in the body column of the cnidarian polyp. We report the pattern of Cnox-2 expression in both the stolonal mat and free stolons of the hydroid Hydractinia symbiolongicarpus. The gene is found to have high levels of expression in the mat similar to that found in the basal portion of the polyp, but it is not detectably expressed in those regions of free stolons where polyps are budded. These findings suggest that the stolonal mat arose via an expansion of the basal ectoderm of the polyp.

We report the isolation and expression of the Hox gene, Cnox-2, in Hydractinia symbiolongicarpus, a hydrozoan displaying division of labor. We found different patterns of aboral-to-oral Cnox-2 expression among polyp polymorphs, and we show that experimental conversion of one polyp type to another is accompanied by concordant alteration in Cnox-2 expression. Our results are consistent with the suggestion that polyp polymorphism, characteristic of hydractiniid hydroids, arose via evolutionary modification of proportioning of head to body column.

Time-lapse video microscopy and image analysis algorithms were used to generate high-resolution time series of the length and volume of a single hydrozoan polyp before and after feeding. A polyp of Podocoryne carnea prior to feeding is effectively static in length and volume. At 20{deg}C, feeding elicits 8-millihertz (mHz) oscillations in polyp length and volume. A polyp connected to a colony by a single stolon displayed an abrupt transition from low-amplitude, 8-mHz oscillations to large-amplitude, 6-mHz oscillations at 1.5-2 h after feeding. The transition was preceded by a substantial decrease in polyp volume and increase in length which coincided with the export of food items from the digestive cavity of the polyp into the colonial gastrovascular system. In contrast, 8-mHz oscillations of a polyp isolated from a colony continued for 12.7 h after feeding, at which time particulates from the digestive cavity were exported into the hydrorhiza and a 4-mHz subharmonic became briefly dominant. Regular oscillatory behavior was terminated by regurgitation at comparable intervals post-feeding in coupled and isolated polyps. These observations are compatible with the hypothesis that the presence of nutrients in the digestive cavity induces polyp oscillations and that release of nutrients into the gastrovascular system similarly induces unfed polyps to oscillate, thereby distributing the contents of the fed polyp throughout the colony., (Copyright © 1999 by Marine Biological Laboratory.)

We report the isolation of an empty spiracles class homeodomain-containing gene, Cn-ems, from the hydrozoan Hydractinia symbiolongicarpus, the first gene of this class characterized in a lower metazoan. Cn-ems was found to be expressed in the head of gastrozooids, specifically in endodermal epithelial cells of the taeniolae of the hypostome. Cn-ems is not expressed in gonozooids, which lack taeniolae. Experimental conversion of the posterior region of the planula larva into head structures up-regulates expression of the gene. These findings establish that the association of ems-class genes with head structures preceded the evolution of bilateral symmetry.

Allorecognition is ubiquitous, or nearly so, amongst colonial invertebrates. Despite the prominent role that such phenomena have played both in evolutionary theory and in on the origin of the vertebrate immune system, unambiguous data on the transmission genetics of fusibility (i.e., the ability of two individuals to fuse upon tissue contact) is lacking for any metazoan outside of the phylum Chordata. We have developed lines of the hydroid Hydractinia symbiolongicarpus (Phylum Cnidaria) inbred for fusibility and here report results of breeding experiments establishing that fusibility segregates as expected for a single locus with codominantly expressed alleles, with one shared allele producing a fusible phenotype. Surveys of fusibility in field populations and additional breeding experiments indicate the presence of an extensive allele series.

The evolutionary history of cnidarian life cycles has been debated since the 1880s, with different hypotheses favored even by current textbooks. Contributing to the disagreement is the fact that the systematic relationships of the four cnidarian classes have received relatively little examination using modern systematic methods. Here we present analyses of class-level relationships based on 18S ribosomal DNA (rDNA) sequence, mitochondrial 16S rDNA sequence, mitochondrial genome structure, and morphological characters. DNA sequences were aligned using a repeatable parsimony-based approach incorporating a range of alignment parameters. Analyses of individual data sets and of all data combined are unanimous in grouping the classes possessing a medusa stage, leaving the holobenthic Anthozoa basal within the phylum.

The polymerase chain reaction was used to survey the oligochaete worm Stylaria lacustris for HOM/Hox type homeobox genes. Twelve fragments were identified and in most cases were assignable to cognate groups on the basis of amino acid similarity. Stylaria appears to have three labial-type genes, a HOX B3 cognate, several genes similar to Antennapedia, and cognates of Abdominal-B and CHox7.

The polychaete worm Ctenodrilus serratus was surveyed for the presence of HOM/HOX and engrailed-type homeobox genes using PCR with degenerate primers. Sixteen unique homeobox fragments were found in surveys of genomic and cDNA with three different primer sets. For three fragments, RACE was employed to obtain additional homeobox sequence and the 3' flanking region. Nine HOM/HOX-type fragments were identified, including putative representatives of the Hox1/lab, Hox2/pb, Hox3, Hox4/Dfd, and Antp/Lox5 cognate groups. Two additional Antp-like fragments could not be assigned specific orthology. Presence of an ortholog of leech Lox2 in addition to a Ubx/abdA-like gene suggests that independent duplications of a single precursor occurred in the annelid and arthropod lineages. No representative of the Hox9/AbdB group was identified. Our results are consistent with a hypothesis of a single HOM/HOX cluster in Ctenodrilus as extensive as that seen in strongly tagmatized arthropods, suggesting that the primitive role of these genes even in overtly metameric animals was something other than specification of overt segmental differentiation. The primers used also detected representatives of six other homeobox classes or families: Xlox (XlHbox8/HTr-A2), Ovx (Chox7), caudal, Prh (proline-rich homeobox), NEC (ceh-9/Tghbox5), and engrailed.

We develop an abstract chemistry, implemented in a lambda-calculus-based modeling platform, and argue that the following features are generic to this particular abstraction of chemistry; hence, they would be expected to reappear if "the tape were run twice": (i) hypercycles of self-reproducing objects arise; (ii) if self-replication is inhibited, self-maintaining organizations arise; and (iii) self-maintaining organizations, once established, can combine into higher-order self-maintaining organizations.

The polymerase chain reaction was used to survey HOM/Hox type homeobox genes in the North American horseshoe crab, Limulus polyphemus. The survey reveals 28 different homeobox fragments possessing 44-80% nucleotide sequence similarity with HOM-C sequences in Drosophila and Hox B sequences in mouse. Limulus has one to four representatives of HOM/Hox cognates when fragments are assigned according to amino acid identity. A parsimony analysis including the Limulus sequences and homologous mouse Hox B and Drosophila HOM-C sequences reveals several instances of monophyletic groupings of Limulus homeoboxes with a Drosophila or mouse gene as the sister branch. Under the current model of HOM/Hox cluster evolution, these results suggest that Limulus has as many as four HOM/Hox type clusters. This is the first evidence suggesting the presence of multiple clusters in a nonvertebrate taxon. Putative homologs of mouse Hoxb-3 in Limulus suggest that the gene was present in the common ancestor of arthropods and vertebrates and has been lost in Drosophila.

We used Random Amplified Polymorphic DNA (RAPD) fingerprinting to address issues of paternity in two odonate species. Amplification artifacts of RAPD markers were controlled by assessing paternity patterns relative to the banding patterns generated by quantitative mixtures of DNA from putative parents ('synthetic offspring'). In the aeshnid dragonfly Anax parthenope, for which the mating histories of both males and females were unknown, we found strong evidence for complete paternity success for the contact guarding male. In the highly polygamous libellulid dragonfly Orthetrum coerulescens, we detected and quantified mixed paternity in sequentially produced offspring clutches and demonstrated that fertilization success is correlated with the duration of copulation. Our results suggest that RAPD fingerprinting is suitable to address issues of paternity in systems which are genetically uncharacterized and produce large offspring clutches.

The phylogenetic relationships of the Recent cnidarian classes remain one of the classic problems in invertebrate zoology. We survey the structure of the mitochondrial genome in representatives of the four extant cnidarian classes and in the phylum Ctenophora. We find that all anthozoan species tested possess mtDNA in the form of circular molecules, whereas all scyphozoan, cubozoan, and hydrozoan species tested display mtDNA in the form of linear molecules. Because ctenophore and all other known metazoan mtDNA is circular, the shared occurrence of linear mtDNA in three of the four cnidarian classes suggests a basal position for the Anthozoa within the phylum.

Clonal plants, fungi, and invertebrate animals often display both intra- and interspecific heterochronic variation in the relative proportions of ramets (e.g., polyps, plantlets) and stolons (or rhizomes, hyphae). Treatment of developing colonies of Podocoryne carnea, a hydractiniid hydroid, with dilute solutions of 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, accelerates the usual ontogenetic trajectory of polyp and stolon production. This morphological heterochrony can be related to the hydrodynamic behavior of the gastrovascular system under the conditions of "loose-coupling" of oxidative phosphorylation produced by DNP. In its normal ontogeny, Hydractinia symbiolongicarpus, a closely related hydractiniid hydroid, not only shows morphological heterochrony similar to that induced in P. carnea by DNP, but also shows a pattern of gastrovascular flow similar to that observed in P. carnea under treatment with DNP. These results support hypotheses linking metabolic activity to heterochronic variation and provide a potentially widely applicable experimental basis for the study of such variation.

King crabs (Family Lithodidae) are among the world's largest arthropods, having a crab-like morphology and a strongly calcified exoskeleton. The hermit crabs, by contrast, have depended on gastropod shells for protection for over 150 million years. Shell-living has constrained the morphological evolution of hermit crabs by requiring a decalcified asymmetrical abdomen capable of coiling into gastropod shells and by preventing crabs from growing past the size of the largest available shells. Whereas reduction in shell-living and acquisition of a crab-like morphology (carcinization) has taken place independently in several hermit crab lineages, and most dramatically in king crabs, the rate at which this process has occurred was entirely unknown. We present molecular evidence that king crabs are not only descended from hermit crabs, but are nested within the hermit crab genus Pagurus. We estimate that loss of the shell-living habit and the complete carcinization of king crabs has taken between 13 and 25 million years.

Homeoboxes have previously been documented from various phyla of triploblastic, coelomate and pseudocoelomate, animals. We report here the first homeoboxes from cnidarians, a phylum of diploblastic organisms thought to occupy a near-basal position in metazoan phylogeny. We have sequenced three partial (77 bp) fragments of Antennapedia (Antp) class homeoboxes from the hydroids Hydractinia symbiolongicarpus and Eleutheria dichotoma. A pair of fragments, Cnox-2-Hs and Cnox-2-Ed, from the two species differ in nucleotide sequences but have identical derived amino acid sequences. A gene tree produced by parsimony analysis shows that these two fragments cluster within the Antp homeobox lineage. The third fragment, Cnox-1, clusters as a sister group of the other Antp class homeoboxes.

The paleobiogeographic histories of three North Atlantic hermit crab lineages were compared with a single-copy DNA-DNA hybridization phylogeny of their symbiotic hydroid genus Hydractinia to test hypotheses of shared history between these host and symbiont lineages. A survey of the geologic literature suggests that two vicariance events in the Quaternary are responsible for existing range disjunctions of the host hermit crab lineages. The Hydractinia phylogeny revealed two distinct clades, one with a primarily northern and the other with a primarily southern distribution. In two of three cases, hydroids associated with closely related hermits on both sides of the range disjunction appear as sister taxa in the phylogeny. A linear scaling between a measure of hydroid sequence divergence and independent geologic estimates of the timing of the vicariant events believed to have established the hermit crab range disjunctions is consistent with the claim of temporal coincidence of cladogenic and vicariance events. These findings provide evidence for shared history of symbiotic associations in two of the three cases., (© 1991 The Society for the Study of Evolution.)

Colonies of hydractiniid hydroids consist of feeding polyps connected by a common gastrovascular system. The gastrovascular system consists of stolons, which enclose gastrovascular canals. Stolons may be fused into a stolonal mat or extend from the periphery of the colony. Hydractinia forms a stolonal mat early in colony development; Podocoryne, on the other hand, does not. To facilitate comparisons of these taxa, we propose a simple shape metric, perimeter/{radical}area, and show that this measure: (1) correlates closely with relative amounts of peripheral stolon and stolonal mat structures in Hydractinia, (2) permits analyses of within- and between-species variation of growth morphology in Podocoryne and Hydractinia, and (3) allows quantitative analysis of breeding studies of Hydractinia, both before and after stolonal mat formation in the progeny.

Colonies of encrusting marine invertebrates are tractable models for the study of competition, because of the relative ease with which observations can be made on the frequency and outcome of overgrowth interactions. Studies of intraspecific competition have found that competition is predicated upon a genetically controlled recognition event, which results in either fusion or rejection. Data are rapidly accumulating in two model systems showing that fusion is associated with somatic cell parasitism and that rejection is associated with overgrowth. Thus, encounters between conspecifics define a choice: to compete at the level of the cell lineage or to compete at the level of the colony. Fusion-rejection genes act to control the units (or targets) of selection., (Copyright © 1990. Published by Elsevier Ltd.)

Competition and cooperation are thought to represent the opposite extremes of organism interactions. I here show that the formation of aggregations in a sessile organism requires cooperation between individuals and that the gregarious pattern of habitat selection generating these aggregations is a response to a density dependence in the outcome of interference competition.

Species of ectoprocts and solitary encrusting animals were subjected in aquaria to homogenates of 11 sympatric species of sponges and colonial ascidians. Five of the nine sponge species and one of the two ascidian species exhibited species-specific allelochemical effects. Evidence suggests that alleochemical provide a wide-spread, specific, and complex mechanism for interference competition for space among natural populations of coral reef organisms. The existence of such species-specific mechanisms may provide a basis for maintenance of diversity in space-limited systems in the absence of high levels of predation and physical disturbance.

The competitive ranking of three marine sessile organisms was determined from overgrowth observations and found to be intrasitive. Overgrowth results were dependent upon relative vertical relief which, in turn, was related to colony area. Discriminant function analysis demonstrates that competitive rankings can be largely predicted on the basis of knowledge of the size-frequency distribution of interacting populations. Because size increases with age for these species, size-dependent competition implies age-dependent competition. The role of age structure in determining the results of inter-specific interactions has been curiously neglected, particularly as it relates to competitive ability, yet the age dependence of competitive ability suggests (i) the occurrence of intransitivity in purely exploitative systems, (ii) a mechanism for frequency-dependent behavior, (iii) the production of limit cycles, and (iv) the possibility of size refugia.

Indirect experimental evidence suggested the possibility that the restoration of blood volume to normal hemorrhage in adult sheep may occur more quickly than in other species that have been studied. To test this hypothesis, we studied unanesthetized chronically catheterized adult female sheep 1-2 wk after splenectomy. An average of 19.6 +/- 1.4% (SE) of their initial blood volume was removed over 10 min. Blood volume restitution at 0.5, 1, 3, 5, 7, 24, and 48 h posthemorrhage averaged 12 +/- 3, 34 +/- 3, 41 +/- 3, 50 +/- 4, 62 +/- 10, 79 +/- 10, and 124 +/- 25%, respectively. Arterial pressure decreased during the hemorrhage and returned to normal within 2 h, whereas venous pressure did not change significantly. No change in blood osmolality occurred. There was a highly significant correlation between blood volume and plasma protein mass (r = 0.98, P less than 10(-6)) during and after the hemorrhage. Thus it appears that the posthemorrhage restoration of blood volume in adult sheep occurs over essentially the same time course as in other species and this appears to be mediated by a restoration of plasma protein mass.