Highly pathogenic avian influenza A(H5N1) virus in a common bottlenose dolphin (Tursiops truncatus) in Florida.

Since late 2021, highly pathogenic avian influenza (HPAI) viruses of A/goose/Guangdong/1/1996 (H5N1) lineage have caused widespread mortality in wild birds and poultry in the United States. Concomitant with the spread of HPAI viruses in birds are increasing numbers of mammalian infections, including wild and captive mesocarnivores and carnivores with central nervous system involvement. Here we report HPAI, A(H5N1) of clade 2.3.4.4b, in a common bottlenose dolphin (Tursiops truncatus) from Florida, United States. Pathological findings include neuronal necrosis and inflammation of the brain and meninges, and quantitative real time RT-PCR reveal the brain carried the highest viral load. Virus isolated from the brain contains a S246N neuraminidase substitution which leads to reduced inhibition by neuraminidase inhibitor oseltamivir. The increased prevalence of A(H5N1) viruses in atypical avian hosts and its cross-species transmission into mammalian species highlights the public health importance of continued disease surveillance and biosecurity protocols.

Robust capital cost optimization of generation and multitimescale storage requirements for a 100% renewable Australian electricity grid.

Transitioning from a fossil-fuel-dependent economy to one based on renewable energy requires significant investment and technological advancement. While wind and solar technologies provide lower cost electricity, enhanced energy storage and transmission infrastructure come at a cost for managing renewable intermittency. Energy storage systems vary in characteristics and costs, and future grids will incorporate multiple technologies, yet the optimal combination of storage technologies and the role of interconnectors in alleviating storage needs are not widely explored. This study focuses on optimal generation-storage capacity requirements to elucidate associated investments. We propose a multitimescale storage solution consisting of three storage categories and an interconnector between Australia's eastern and western grids. Subsequently, through an extensive sensitivity analysis, we investigate the impact of specific storage technologies and cost variations. Our findings demonstrate that the proposed interconnector offers a cost-effective solution, reducing generation and storage power capacity needs by 6 and 14%, respectively, resulting in 4% savings on overall investment costs. Moreover, the study's sensitivity analysis reveals that wind generation provides 50-70% of the energy demand for the least-cost solution. Despite storage inefficiencies, long-duration storage would need to be deployed to support power capacity for 2-4 days, representing 15-40% of peak demand, depending on future technology costs. Subsequently, achieving a fully renewable electricity sector in Australia requires a significant expansion of generation and storage infrastructure, with a 13-fold increase in storage power capacity and a 40-fold increase in storage energy capacity compared to existing levels.

Experimental infection of domestic turkeys with lymphoproliferative disease virus of North American origin.

Lymphoproliferative disease virus (LPDV) was first documented in wild turkeys in North America in 2009. LPDV infection is often subclinical but can manifest as lymphoid proliferation or round cell neoplasia. Despite high prevalence across many sampled areas corresponding to declining populations of wild turkeys, knowledge regarding LPDV pathogenesis, risk factors for disease development, and associated impacts on population dynamics are unknown. To understand transmission, viral shedding, and tissue tropism, we inoculated 21 domestic turkeys via the oral cavity, crop, nasal cavity, subcutis, or coelomic cavity. For 12 weeks, oropharyngeal swabs, cloacal swabs, and whole blood were collected weekly. At 1 week postinoculation, 3 turkeys (3/21; 14%) had detectable LPDV proviral DNA in blood by polymerase chain reaction, and 10 developed DNAemia (50%; 10/20) by 12 weeks. LPDV proviral DNA was intermittently detected in oropharyngeal and cloacal swabs. Splenomegaly was the most consistent gross finding in DNAemic birds (8/11; 73%). Lymphoid hyperplasia in the spleen was the most significant microscopic finding (9/11; 82%). Three turkeys (3/11; 27%) developed round cell neoplasia characterized by sheets of pleomorphic, round to polygonal cells in the adrenal gland, bone marrow, skin, small intestine, and/or spleen. LPDV was detected in the spleen and bone marrow from all turkeys with DNAemia and all neoplasms. Our study establishes that infection and disease with North American LPDV from wild turkeys can be experimentally reproduced in domestic turkeys, laying the groundwork for future investigations into LPDV pathogenesis, development of diagnostic techniques, and understanding the impacts of LPDV on wild turkey populations.

Unrecognized diversity of mammalian orthoreoviruses in North American bats.

Bats have recently been identified as potential reservoir hosts for mammalian orthoreoviruses (MRVs) throughout Europe and China. Here we present the first evolutionary and biological characterization of bat-borne MRVs in North America, including phylogenomic analysis, in vitro relative infectivity in bat and other mammalian cell cultures, host cell receptor specificity, and epifluorescence microscopy of viral factory formation. Through genetic and phylogenetic comparisons, we show that two divergent MRV serotype 2 (T2) strains - isolated from a silver-haired bat (Lasionycteris noctivagans) and a big brown bat (Eptesicus fuscus) from Pennsylvania, USA - provide an evolutionary link to an MRV strain (T2W) recovered from an 8-week-old infant who died in Winnipeg, Manitoba, Canada in 1997. Although these findings suggest North American bats may represent a previously unrecognized source for the cross-species transmission of MRVs to other animals, including humans, the ecology and epidemiology of MRVs in wildlife remain enigmatic.

Hip osteoarthritis: A novel network analysis of subchondral trabecular bone structures.

Hip osteoarthritis (HOA) is a degenerative joint disease that leads to the progressive destruction of subchondral bone and cartilage at the hip joint. Development of effective treatments for HOA remains an open problem, primarily due to the lack of knowledge of its pathogenesis and a typically late-stage diagnosis. We describe a novel network analysis methodology for microcomputed tomography (micro-CT) images of human trabecular bone. We explored differences between the trabecular bone microstructure of femoral heads with and without HOA. Large-scale automated extraction of the network formed by trabecular bone revealed significant network properties not previously reported for bone. Profound differences were discovered, particularly in the proximal third of the femoral head, where HOA networks demonstrated elevated numbers of edges, vertices, and graph components. When further differentiating healthy joint and HOA networks, the latter showed fewer small-world network properties, due to decreased clustering coefficient and increased characteristic path length. Furthermore, we found that HOA networks had reduced length of edges, indicating the formation of compressed trabecular structures. In order to assess our network approach, we developed a deep learning model for classifying HOA and control cases, and we fed it with two separate inputs: (i) micro-CT images of the trabecular bone, and (ii) the network extracted from them. The model with plain micro-CT images achieves 74.6% overall accuracy while the trained model with extracted networks attains 96.5% accuracy. We anticipate our findings to be a starting point for a novel description of bone microstructure in HOA, by considering the phenomenon from a graph theory viewpoint.

Implementation of a Constipation Action Plan for Patients Discharged From a Pediatric Hospitalist Service.

OBJECTIVE: The objective of this study was to determine the effect of a pharmacist-led constipation action plan on the rate of health care utilization. METHODS: We conducted a prospective research study of patients 2 to 18 years of age admitted to a pediatric hospitalist service for constipation. A study pharmacist developed a patient-specific constipation action plan for each enrolled patient. Data were collected from the electronic medical record, patient/caregiver interview, and follow-up phone calls completed by a pharmacist. The primary outcome was to determine the effect of a pharmacist-led constipation action plan on the rate of health care utilization. RESULTS: Twenty-seven patients were enrolled in the study. Median (range) age was 9 (2-18) years. Health care utilization of the entire study population decreased from approximately 8.7 encounters per month prior to implementation to approximately 3 encounters per month after implementation. Patients also reported an increase in daily bowel movements from approximately 1 per day prior to implementation to 2 per day post implementation. CONCLUSIONS: Health care utilization appeared to decrease after implementation of a patient-specific, pharmacist-led constipation action plan.

The development of tumour vascular networks.

The growth of solid tumours relies on an ever-increasing supply of oxygen and nutrients that are delivered via vascular networks. Tumour vasculature includes endothelial cell lined angiogenesis and the less common cancer cell lined vasculogenic mimicry (VM). To study and compare the development of vascular networks formed during angiogenesis and VM (represented here by breast cancer and pancreatic cancer cell lines) a number of in vitro assays were utilised. From live cell imaging, we performed a large-scale automated extraction of network parameters and identified properties not previously reported. We show that for both angiogenesis and VM, the characteristic network path length reduces over time; however, only endothelial cells increase network clustering coefficients thus maintaining small-world network properties as they develop. When compared to angiogenesis, the VM network efficiency is improved by decreasing the number of edges and vertices, and also by increasing edge length. Furthermore, our results demonstrate that angiogenic and VM networks appear to display similar properties to road traffic networks and are also subject to the well-known Braess paradox. This quantitative measurement framework opens up new avenues to potentially evaluate the impact of anti-cancer drugs and anti-vascular therapies.

Impact of anaemia at discharge following colorectal cancer surgery.

OBJECTIVES: Preoperative anaemia is common in patients with colorectal cancer and increasingly optimised prior to surgery. Comparably little attention is given to the prevalence and consequences of postoperative anaemia. We aimed to investigate the frequency and short- or long-term impact of anaemia at discharge following colorectal cancer resection. METHODS: A dedicated, prospectively populated database of elective laparoscopic colorectal cancer procedures undertaken with curative intent within a fully implemented ERAS protocol was utilised. The primary endpoint was anaemia at time of discharge (haemoglobin (Hb) < 120 g/L for women and < 135 g/L for men). Patient demographics, tumour characteristics, operative details and postoperative outcomes were captured. Median follow-up was 61 months with overall survival calculated with the Kaplan-Meier log rank method and Cox proportional hazard regression based on anaemia at time of hospital discharge. RESULTS: A total of 532 patients with median 61-month follow-up were included. 46.4% were anaemic preoperatively (cohort mean Hb 129.4 g/L ± 18.7). Median surgical blood loss was 100 mL (IQR 0-200 mL). Upon discharge, most patients were anaemic (76.6%, Hb 116.3 g/L ± 14, mean 19 g/L ± 11 below lower limit of normal, p < 0.001). 16.7% experienced postoperative complications which were associated with lower discharge Hb (112 g/L ± 12 vs. 117 g/L ± 14, p = 0.001). Patients discharged anaemic had longer hospital stays (7 [5-11] vs. 6 [5-8], p = 0.037). Anaemia at discharge was independently associated with reduced overall survival (82% vs. 70%, p = 0.018; HR 1.6 (95% CI 1.04-2.5), p = 0.034). CONCLUSION: Anaemia at time of discharge following elective laparoscopic colorectal cancer surgery and ERAS care is common with associated negative impacts upon short-term clinical outcomes and long-term overall survival.

Retrospective Assessment of the Use of Liposomal Bupivacaine in Lumbar Fusions in Immediate Postoperative Hospital Care.

BACKGROUND: Liposomal bupivacaine (LB) is approved by the U.S. Food and Drug Administration for administration into surgical sites for postsurgical analgesia. The liposomal formulation allows for sustained effects up to 72 hours. METHODS: A retrospective study assessed patients undergoing lumbar interbody surgery. Visual analog scale pain scores and amount of opioids consumed were recorded at 12-hour intervals for 72 hours postoperatively, as were patterns of discharge and hospital length of stay (LOS). RESULTS: A total of 122 patients (97 LB vs. 25 control group) were reviewed. Median LOS was shorter in the LB cohort compared with controls (1.94 vs. 3.08 days, respectively; P = 0.0043). When assessing the percentage of discharges between groups at 12-hour intervals, there were significantly more discharges in the LB cohort at 36-48 hours (P = 0.0226), and no differences elsewhere. There was a decrease in intravenous opioids consumed at 48-60 hours in the LB cohort compared with controls (P = 0.0494), a difference not detected at other time points or with oral or total opioids. Mean visual analog scale scores were significantly higher in the LB cohort compared with controls at 0-12 hours (5.2 vs. 3.9, respectively; P = 0.0079), but insignificantly different subsequently up to 72 hours. The LB cohort and controls were not significantly different in total amount of opioids consumed, overall pain scores, or regarding how the opioid amount consumed or pain scores changed over time. CONCLUSIONS: The use of LB in lumbar interbody fusion decreases patients' LOS but has little effect on reducing overall pain scores or opioid use in the 72-hour postoperative hospital period.

Publisher Correction: Truels and strategies for survival.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Bevacizumab as adjuvant therapy for recurrent respiratory papillomatosis in an infant.

Recurrent Respiratory Papillomatosis (RRP) is a benign disease of the airway that can result in symptoms ranging from mild dysphonia to respiratory distress to respiratory failure related to colonization of the lung parenchyma. It is a disease that typically begins in childhood and can require treatment indefinitely, though may remit in adolescence. Although treatment includes surgical management, certain cases require adjuvant therapy. Many therapies have been tried over the years with varying levels of success. Our patient presented as a 7 month old male in respiratory distress, who was subsequently diagnosed with RRP. He has required a tracheostomy, ventilation, and frequent surgical debridement for the last 20 months. Due to the aggressiveness of his disease, he was started on systemic bevacizumab (Avastin) in an effort to stabilize his lesions. Though early effect seemed apparent based on Derkay scores, systemic bevacizumab has failed to elicit clinical improvement in our patient. He remains with a tracheostomy receiving bevacizumab 10 mg/kg as an intermittent infusion approximately every 4 weeks along with surgical debridement with little to no clinical improvement thus far. In light of the recent successes with bevacizumab therapy, this case highlights the difficulty in finding new treatment for this disease.

Distinct Lineages of Feline Parvovirus Associated with Epizootic Outbreaks in Australia, New Zealand and the United Arab Emirates.

Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had not been reported for several decades. Case data from 989 cats and clinical samples from additional 113 cats were obtained to determine the cause of the outbreaks and epidemiological factors involved. Most cats with FPL were shelter-housed, 9 to 10 weeks old at diagnosis, unvaccinated, had not completed a primary vaccination series or had received vaccinations noncompliant with current guidelines. Analysis of parvoviral VP2 sequence data confirmed that all FPL cases were caused by FPV and not CPV. Phylogenetic analysis revealed that each of these outbreaks was caused by a distinct FPV, with two virus lineages present in eastern Australia and virus movement between different geographical locations. Viruses from the UAE outbreak formed a lineage of unknown origin. FPV vaccine virus was detected in the New Zealand cases, highlighting the difficulty of distinguishing the co-incidental shedding of vaccine virus in vaccinated cats. Inadequate vaccination coverage in shelter-housed cats was a common factor in all outbreaks, likely precipitating the multiple re-emergence of infection events.

Limited Intrahost Diversity and Background Evolution Accompany 40 Years of Canine Parvovirus Host Adaptation and Spread.

Canine parvovirus (CPV) is a highly successful pathogen that has sustained pandemic circulation in dogs for more than 40 years. Here, integrating full-genome and deep-sequencing analyses, structural information, and in vitro experimentation, we describe the macro- and microscale features that accompany CPV's evolutionary success. Despite 40 years of viral evolution, all CPV variants are more than ∼99% identical in nucleotide sequence, with only a limited number (<40) of substitutions becoming fixed or widespread during this time. Notably, most substitutions in the major capsid protein (VP2) gene are nonsynonymous, altering amino acid residues that fall within, or adjacent to, the overlapping receptor footprint or antigenic regions, suggesting that natural selection has channeled much of CPV evolution. Among the limited number of variable sites, CPV genomes exhibit complex patterns of variation that include parallel evolution, reversion, and recombination, compromising phylogenetic inference. At the intrahost level, deep sequencing of viral DNA in original clinical samples from dogs and other host species sampled between 1978 and 2018 revealed few subconsensus single nucleotide variants (SNVs) above ∼0.5%, and experimental passages demonstrate that substantial preexisting genetic variation is not necessarily required for rapid host receptor-driven adaptation. Together, these findings suggest that although CPV is capable of rapid host adaptation, a relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since its initial emergence have inhibited the long-term accumulation of genetic diversity. Hence, continuously high levels of inter- and intrahost diversity are not necessarily required for virus host adaptation.IMPORTANCE Rapid mutation rates and correspondingly high levels of intra- and interhost diversity are often cited as key features of viruses with the capacity for emergence and sustained transmission in a new host species. However, most of this information comes from studies of RNA viruses, with relatively little known about evolutionary processes in viruses with single-stranded DNA (ssDNA) genomes. Here, we provide a unique model of virus evolution, integrating both long-term global-scale and short-term intrahost evolutionary processes of an ssDNA virus that emerged to cause a pandemic in a new host animal. Our analysis reveals that successful host jumping and sustained transmission does not necessarily depend on a high level of intrahost diversity nor result in the continued accumulation of high levels of long-term evolution change. These findings indicate that all aspects of the biology and ecology of a virus are relevant when considering their adaptability.

Factors Predicting Operative Difficulty of Laparoscopic Total Mesorectal Excision.

BACKGROUND: Laparoscopic total mesorectal excision is a challenging procedure requiring high-quality surgery for optimal outcomes. Patient, tumor, and pelvic factors are believed to determine difficulty, but previous studies were limited to postoperative data. OBJECTIVE: This study aimed to report factors predicting laparoscopic total mesorectal excision performance by using objective intraoperative assessment. DESIGN: Data from a multicenter laparoscopic total mesorectal excision randomized trial (ISRCTN59485808) were reviewed. SETTING: This study was conducted at 4 centers in the United Kingdom. PATIENTS AND INTERVENTION: Seventy-one patients underwent elective laparoscopic total mesorectal excision for rectal adenocarcinoma with curative intent: 53% were men, mean age was 69 years, body mass index was 27.7, tumor height was 8.5 cm, 24% underwent neoadjuvant therapy, and 25% had previous surgery. MAIN OUTCOME MEASURES: Surgical performance was assessed through the identification of intraoperative adverse events by using observational clinical human reliability analysis. Univariate analysis and multivariate binomial regression were performed to establish factors predicting the number of intraoperative errors, surgeon-reported case difficulty, and short-term clinical and histopathological outcomes. RESULTS: A total of 1331 intraoperative errors were identified from 365 hours of surgery (median, 18 per case; interquartile range, 16-22; and range, 9-49). No patient, tumor, or bony pelvimetry measurement correlated with total or pelvic error count, surgeon-reported case difficulty, cognitive load, operative data, specimen quality, number or severity of 30-day morbidity events and length of stay (all r not exceeding ±0.26, p > 0.05). Mesorectal area was associated with major intraoperative adverse events (OR, 1.09; 95%CI, 1.01-1.16; p = 0.015) and postoperative morbidity (OR, 1.1; 95% CI, 1.01-1.2; p = 0.033). Obese men were subjectively reported as harder cases (24 vs 36 mm, p = 0.042), but no detrimental effects on performance or outcomes were seen. LIMITATIONS: Our sample size is modest, risking type II errors and overfitting of the statistical models. CONCLUSION: Patient, tumor, and bony pelvic anatomical characteristics are not seen to influence laparoscopic total mesorectal excision operative difficulty. Mesorectal area is identified as a risk factor for intraoperative and postoperative morbidity. See Video Abstract at http://links.lww.com/DCR/B35. FACTORES QUE PREDICEN LA DIFICULTAD OPERATIVA DE LA ESCISIÓN MESORRECTAL TOTAL LAPAROSCÓPICA: La escisión mesorrectal total laparoscópica es un procedimiento desafiante. Para obtener resultados óptimos, se requiere cirugía de alta calidad. Se cree que, factores como el paciente, el tumor y la pelvis, determinan la dificultad, pero estudios previos solamente se han limitado a datos postoperatorios.Informar de los factores que predicen el resultado de la escisión mesorrectal total laparoscópica, mediante una evaluación intraoperatoria objetiva.Datos de un ensayo multicéntrico y randomizado de escisión mesorrectal total laparoscópica (ISRCTN59485808).Cuatro centros del Reino Unido.Un total de 71 pacientes fueron sometidos a escisión mesorrectal total laparoscópica electiva, para adenocarcinoma rectal con intención curativa. 53% hombres, edad media, índice de masa corporal y altura del tumor 69, 27.7 y 8.5 cm respectivamente, 24% terapia neoadyuvante y 25% cirugía previa.Rendimiento quirúrgico evaluado mediante la identificación de eventos intraoperatorios adversos, mediante el análisis clínico observacional de confiabilidad humana. Se realizaron análisis univariado y la regresión binomial multivariada para establecer factores que predicen el número de errores intraoperatorios, reportes del cirujano sobre la dificultad del caso y los resultados clínicos e histopatológicos a corto plazo.Se identificaron un total de 1,331 errores intraoperatorios en 365 horas de cirugía (media de 18 por caso, IQR 16-22, rango 9-49). Ningún paciente, tumor o medición de pelvimetría pélvica, se correlacionó con la cuenta de errores pélvicos o totales, reporte del cirujano sobre dificultad del caso, carga cognitiva, datos operativos, calidad de la muestra, número o gravedad de eventos de morbilidad de 30 días y duración de la estadía (todos r <± 0.26, p > 0.05). El área mesorrectal se asoció con eventos adversos intraoperatorios importantes (OR, 1.09; IC 95%, 1.01-1.16; p = 0.015) y morbilidad postoperatoria (OR, 1.1; IC 95%, 1.01-1.2; p = 0.033). Como información subjetiva, hombres obesos fueron casos más difíciles (24 mm frente a 36 mm, p = 0.042) pero no se observaron efectos perjudiciales sobre el rendimiento o los resultados.Nuestro tamaño de muestra es un modesto riesgo de errores de tipo II y el sobreajuste de los modelos estadísticos.No se observa que las características anatómicas del paciente, tumor y pelvis ósea influyan en la dificultad operatoria de la escisión mesorrectal laparoscópica total. El área mesorrectal se identifica como un factor de riesgo para la morbilidad intraoperatoria y postoperatoria. Vea el resumen del video en http://links.lww.com/DCR/B35.

Truels and strategies for survival.

The truel is a three person competition that generalises the classic duel. In this game three players try to eliminate each other in a series of one-to-one duels until there is only one survivor. The players' marksmanship, shooting order and strategies for choosing a target play a significant role in individual's survival probability. Strategies such as shooting into the air (abstention), shooting at the strongest opponent, and shooting at the weakest opponent have been analysed in the previous literature. In this paper, for the first time, we consider suicidal and random strategies that can be chosen by the weaker player. We show that although there is no possible highest probability region for weakest player adopting suicidal strategy, the player may increase the survival probability via switching between suicidal and abstention strategies randomly. In addition, we demonstrate that there is a narrow survival area for the weakest player when the player aims randomly at two other opponents, and eventually the area fades away if the player fires randomly at himself or the other two opponents.

Bayesian Phylogenetic Analysis of Avipoxviruses from North American Wild Birds Demonstrates New Insights into Host Specificity and Interspecies Transmission.

Avian pox is commonly diagnosed in a variety of North American wild and domestic birds, yet little is known about the evolutionary relationships among the causative poxviruses. This study aimed to determine the phylogenetic relationships among isolates identified in different avian host species to better characterize the host range of specific viral strains and compare the genetic variability within and between viral clades. Skin lesions grossly and microscopically consistent with poxvirus infection from 82 birds collected in Canada, the United States, and the U.S. Virgin Islands were included in this study. A total of 12 avian species were represented; the most common species sampled were wild turkeys (Meleagris gallopavo), mourning doves (Zenaida macroura), and American crows (Corvus brachyrhynchos). Poxvirus samples from these birds were genotyped using PCR that targeted the 4b core protein gene followed by amplicon sequencing. Bayesian phylogenetic analyses of these viruses, in conjunction with publicly available sequences, representing avipoxvirus strains from six continents revealed statistically significant monophyletic clades based on genetic distances of sequences within and between observed clades. Genetic variation within the fowlpox clade was low compared to the canarypox clade. Host and geographic origins of viral isolates revealed overall clustering of viral strains within avian species, with a few exceptions. No genetic differences were observed between viruses from Canada and the United States within individual species. These results are novel in their characterization and comparison of the phylogenetic relationships of poxvirus isolates in wild bird species from North America. Further, we provide new data on the level of host specificity and specific strains circulating in North America.

El análisis filogenético bayesiano de los avipoxvirus de las aves silvestres de América del Norte demuestra nuevos conocimientos sobre la especificidad del huésped y la transmisión interespecífica. La viruela aviar se diagnostica comúnmente en una variedad de aves silvestres y domésticas de América del Norte, pero se sabe poco sobre las relaciones evolutivas entre los poxvirus. Este estudio tuvo como objetivo determinar las relaciones filogenéticas entre aislamientos identificados en diferentes especies de hospedadores aviares para caracterizar mejor el rango de hospedadores de cepas virales específicas y comparar la variabilidad genética dentro y entre los clados virales. Se incluyeron en este estudio lesiones cutáneas que eran consistentes macro y microscópicamente con la infección por poxvirus de 82 aves recolectadas en Canadá, Estados Unidos y las Islas Vírgenes de los Estados Unidos. Un total de 12 especies de aves fueron representadas; las especies más comunes en la muestra fueron los pavos silvestres (Meleagris gallopavo), huilota común (Zenaida macroura) y cuervos americanos (Corvus brachyrhynchos). Las muestras de poxvirus de estas aves fueron genotipadas mediante PCR que se enfocó en el gene de la proteína central 4b seguido de secuenciación de amplicón. Los análisis filogenéticos bayesianos de estos virus, junto con las secuencias disponibles públicamente, que representan cepas de avipoxvirus de seis continentes revelaron clados monofiléticos estadísticamente significativos basados en distancias genéticas de las secuencias dentro y entre los clados observados. La variación genética dentro del clado de la viruela del pollo fue baja en comparación con el clado de virus de canario. El huésped y los orígenes geográficos de los aislamientos virales revelaron un agrupamiento general de cepas virales dentro de las especies aviares, con algunas excepciones. No se observaron diferencias genéticas entre los virus de Canadá y los Estados Unidos dentro de las especies individuales. Estos resultados son novedosos en la caracterización y comparación de las relaciones filogenéticas de los aislados de poxvirus en especies de aves silvestres de América del Norte. Además, se proporcionan nuevos datos sobre el nivel de especificidad del huésped y las cepas específicas que circulan en América del Norte. Key words: Bayesian analysis, mourning dove, phylogenetic, poxvirus, sequencing, wild turkey, 4b gene.

On detection of periodicity in C-reactive protein (CRP) levels.

C-reactive protein (CRP) is an acute-phase plasma protein that can be used as a biomarker for activation of the immune system. A spectral analysis of CRP level over time for patients with gynaecological tumours has been reported by Madondo et al., using a periodogram method, suggesting that there is no significant periodicity in the data. In our study, we investigate the impact of low sample number on periodogram analysis, for non-uniform sampling intervals-we conclude that data of Madondo et al. cannot rule out periodic behaviour. The search for patterns (periodic or otherwise) in the CRP time-series is of interest for providing a cue for the optimal times at which cancer therapies are best administered. In this paper we show (i) there is no evidence to rule out periodicity in CRP levels, and (ii) we provide a prescription for the minimum data sample rate required in future experiments for improved testing of a periodic CRP signal hypothesis. The analysis we provide may be used for establishing periodicity in any short time-series signal that is observed without a priori information.

Complex and Dynamic Interactions between Parvovirus Capsids, Transferrin Receptors, and Antibodies Control Cell Infection and Host Range.

Antibody and receptor binding are key virus-host interactions that control host range and determine the success of infection. Canine and feline parvovirus capsids bind the transferrin receptor type 1 (TfR) to enter host cells, and specific structural interactions appear necessary to prepare the stable capsids for infection. Here, we define the details of binding, competition, and occupancy of wild-type and mutant parvovirus capsids with purified receptors and antibodies. TfR-capsid binding interactions depended on the TfR species and varied widely, with no direct relationship between binding affinity and infection. Capsids bound feline, raccoon, and black-backed jackal TfRs at high affinity but barely bound canine TfRs, which mediated infection efficiently. TfRs from different species also occupied capsids to different levels, with an estimated 1 to 2 feline TfRs but 12 black-backed jackal TfRs binding each capsid. Multiple alanine substitutions within loop 1 on the capsid surface reduced TfR binding but substitutions within loop 3 did not, suggesting that loop 1 directly engaged the TfR and loop 3 sterically affected that interaction. Binding and competition between different TfRs and/or antibodies showed complex relationships. Both antibodies 14 and E competed capsids off TfRs, but antibody E could also compete capsids off itself and antibody 14, likely by inducing capsid structural changes. In some cases, the initial TfR or antibody binding event affected subsequent TfR binding, suggesting that capsid structure changes occur after TfR or antibody binding and may impact infection. This shows that precise, host-specific TfR-capsid interactions, beyond simple attachment, are important for successful infection.IMPORTANCE Host receptor binding is a key step during viral infection and may control both infection and host range. In addition to binding, some viruses require specific interactions with host receptors in order to infect, and anti-capsid antibodies can potentially disrupt these interactions, leading to neutralization. Here, we examine the interactions between parvovirus capsids, the receptors from different hosts, and anti-capsid antibodies. We show that interactions between parvovirus capsids and host-specific TfRs vary in both affinity and in the numbers of receptors bound, with complex effects on infection. In addition, antibodies binding to two sites on the capsids had different effects on TfR-capsid binding. These experiments confirm that receptor and antibody binding to parvovirus capsids are complex processes, and the infection outcome is not determined simply by the affinity of attachment.

Does the number of operating specialists influence the conversion rate and outcomes after laparoscopic colorectal cancer surgery?

BACKGROUND: Laparoscopic techniques in colorectal surgery have been widely utilised due to short-term patient benefits but conversion to open surgery is associated with adverse short- and long-term patient outcomes. The aim of this study was to investigate the influence of dual specialist operating on the conversion rate and patient outcomes following laparoscopic colorectal surgery. METHODS: A prospectively populated colorectal cancer surgery database was reviewed. Cases were grouped into single or dual consultant procedures. Cluster analysis and odds ratio (OR) were used to identify risk factors for conversion. Primary outcome measures were conversion to open and five year overall survival (OS) calculated using the Kaplan-Meier log-rank method. RESULTS: 750 patients underwent laparoscopic colorectal cancer resection between 2002 and 2015 (median age 73, 319 (42.5%) female, 282 (37.6%) rectal malignancies, 135 patients (18%) had two consultants). The single surgeon conversion rate was 20.4% compared to 5.5% for dual operating (OR 4.4, 95% CI 1.87-10.2, p < 0.001). There were no demographic or tumour differences between the laparoscopic/converted and number of surgeon groups. Two-step cluster analysis identified cluster I (lower risk) 406 patients, 8% converted and cluster II (higher risk) 261 patients, conversion rate 30%. Median follow-up was 48 months (range 0-168). Five-year OS was significantly inferior for both converted and single surgeon cases (63% vs. 77%, p < 0.001 and 61% vs. 70%, p = 0.033, respectively). CONCLUSION: In selected colorectal cancer patients operated by fully trained laparoscopic surgeons, we observed a reduction in conversion with associated long-term survival benefit from dual operating specialists.