People use math as a weapon: critical mathematics consciousness in the time of COVID-19.

The emergence of the COVID-19 pandemic has brought increased attention to the critical mathematical literacy of citizens in the United States and around the world. A statistically and mathematically literate society is crucial for ensuring that citizens are able to sift through political rhetoric to maintain life-saving procedures such as social distancing and other infection dampening efforts. Additionally, recent civil unrest due to the disproportionate killings of Black men by police provokes investigation into the public's mathematical literacy. In this paper, we investigate adolescent students' critical mathematics consciousness and mathematics literacy as they reason through two interview tasks on the coronavirus and police shooting data. Drawing on Frankenstein's program of Critical Mathematics Education, we introduce an analytic framework for documenting the critical mathematics consciousness of adolescent students. We interviewed fifteen 14- to 16-year-old students as they solved five tasks designed to elicit their critical and ethical mathematical awareness. Our findings indicate that students exhibit very little critical mathematics consciousness in the context of the police problem but show awareness that data can be presented in ways that manipulate the public's emotions in the coronavirus problem. We conclude the paper with a discussion of implications for designing future instruction to support students' growth in critical mathematics consciousness.

Evaluating the ALERT algorithm for local outbreak onset detection in seasonal infectious disease surveillance data.

Estimation of epidemic onset timing is an important component of controlling the spread of seasonal infectious diseases within community healthcare sites. The Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm uses a threshold-based approach to suggest incidence levels that historically have indicated the transition from endemic to epidemic activity. In this paper, we present the first detailed overview of the computational approach underlying the algorithm. In the motivating example section, we evaluate the performance of ALERT in determining the onset of increased respiratory virus incidence using laboratory testing data from the Children's Hospital of Colorado. At a threshold of 10 cases per week, ALERT-selected intervention periods performed better than the observed hospital site periods (2004/2005-2012/2013) and a CUSUM method. Additional simulation studies show how data properties may effect ALERT performance on novel data. We found that the conditions under which ALERT showed ideal performance generally included high seasonality and low off-season incidence.

Response to Multi-Line Chemotherapy in Non-Serous Epithelial Ovarian Cancer.

OBJECTIVES: To describe the response rate to chemotherapy, rates of recurrence, and overall survival in patients with non-serous epithelial ovarian cancers. METHODS: This retrospective cohort study used the Manitoba Cancer Registry to identify all women with non-serous epithelial ovarian, fallopian, or peritoneal cancer treated between 1995 and 2010. Chart review entailed extracting information regarding therapy and outcomes. All patients with recurrence were identified and response to chemotherapy was assessed. RESULTS: We identified 392 patients with non-serous ovarian cancers, 192 of whom received chemotherapy in the first-line setting. Optimal debulking resulted in improvements in rates of recurrence and overall survival (P < 0.001). Histology did not have an effect on recurrence or overall survival. Forty-eight patients (25%) had a recurrence and received second-line therapy, and 21 (11%) received third-line therapy. Response rates were similar regardless of histology. In the second-line setting, 40.9%-83.3% of patients (other > mucinous > clear cell > endometrioid) and in the third-line setting, 33.3%-75.0% of patients (other > mucinous > clear cell > endometrioid) received >6 lines of chemotherapy. Twenty-three percent of patients experienced a recurrence within 2 years of first-line therapy. Two-year survival was 79.4% after first-line treatment, 27.6% after second-line treatment, and 19.5% after third-line treatment. CONCLUSION: Patients with clear cell ovarian cancer had chemotherapy continuation rates similar to those of previously reported studies. This is one of the first studies reporting response rates for mucinous and endometrioid subtypes. Recurrent disease responds to treatment with second- and third-line therapy, emphasizing the importance of offering patients subsequent lines of chemotherapy for disease management. Further studies are needed to determine the optimal regimen.

Comparison of Herpes Simplex Virus PCR with Culture for Virus Detection in Multisource Surface Swab Specimens from Neonates.

The American Academy of Pediatrics currently recommends herpes simplex virus (HSV) culture or PCR for testing of swabs of the conjunctivae, mouth, nasopharynx, and rectum (surface swabs) from neonates. The objectives of this study were to compare the performance and time to results of HSV PCR with those of HSV culture with surface swabs from neonates. Banked multisource surface swab samples that were collected from infants less than or equal to 30 days old from January 2017 to December 2017 and that had previously been cultured for HSV were identified and tested retrospectively by HSV PCR. Surface swab samples from 97 patients were included in the study. Of these 97 patients, 7 (7%) had clinical HSV disease. Of the 7 neonates with HSV disease, 3 (42.9%) had surface swabs positive by culture and 6 (85.7%) had swabs positive by PCR. Limiting the analysis to specimens that were positive only by culture or only by PCR, the specificity for both methods was 100%, but the sensitivity of PCR was 100%, whereas it was 50% for culture. During the study period, 341 HSV cultures and 426 HSV PCRs were performed. The median time from swab collection to reporting of results was 7.6 days (interquartile range [IQR], 7.1 to 7.9 days) for culture and 0.8 days (IQR, 0.6 to 1.0 days) for PCR. HSV PCR of surface swabs from neonates was considerably more rapid and sensitive than HSV culture without yielding false-positive results. Although larger studies are needed to support our findings, strong consideration should be given to utilize PCR instead of culture for the detection of HSV in surface swabs from neonates.

Vulvar postoperative care, gestalt or evidence based medicine? A comprehensive systematic review.

OBJECTIVE: This paper reviews all current literature for vulvar postoperative care, and forms a summary of evidence based practice. DATA SOURCES: Scopus, Cochrane Library, CINHAL, Web of Science Core Collection, PubMed, Embase, Google Scholar, clinicaltrials.gov and Medline databases were searched. METHODS OF STUDY SELECTION: Various combinations of key-terms were used to identify relevant articles. All identified primary research articles and review articles were then examined with their references in order to identify further relevant studies. The literature was examined within gynecology, gynecologic oncology, surgical oncology, urology, plastic surgery and dermatology. TABULATION, INTEGRATION AND RESULTS: A total of 199 studies were reviewed and 80 were included in this paper. All relevant studies pertaining to the subject were included. Studies were excluded if there was no relevance to the review as deemed by both authors. CONCLUSION: There remains much room for improvement to minimize postoperative stay, decrease the chances of morbidity and improve patient outcome and satisfaction, while establishing standardized care pathways. Further research and clinical trials are needed in this area to help us to provide evidence-based care to our postoperative vulvar patient population.

Utilizing community and voluntary sector partnerships to survey and compare the health outcomes of hard-to- reach groups to the wider community-the EURO- URHIS 2 Hard-to-Reach Project.

Background: This article describes the Hard-to-Reach (HtR) Project that was developed to capture health and lifestyle data from groups who are HtR by postal surveys within the larger EURO-URHIS 2 project. By collaborating with partner organizations, data were collected using standard survey tools, allowing for comparison with the wider population. Following a scoping exercise to determine which groups were HtR in Greater Manchester, black and minority ethnic (BME) groups and students were selected. BME groups were surveyed through partnership with Community and Voluntary Sector Organizations (CVSOs). Language barriers were addressed through the recruitment of volunteer interpreters. Students were surveyed by accessing university premises. Fifteen survey visits took place at nine CVSOs and five visits to University facilities. In total, 144 eligible surveys were collected. There were significant differences for both HtR groups, compared with Greater Manchester and the EURO-URHIS 2 mean. Both HtR groups had worse outcomes than both Greater Manchester and EURO-URHIS 2 for psychological problems. In addition, students had worse outcomes for passive smoking, binge drinking, use of cannabis, lack of access to green spaces, less sense of belonging and social cohesion and damp or mildewed homes, and better outcomes for self-perceived health and overweight and obesity. BME had in addition worse outcomes than both Greater Manchester and EURO-URHIS 2 for long-standing restrictive illness. Despite the limitations of this study, the development of this methodology allowed for the collection of comparable data, showing up statistically significant differences between the HtR populations and the wider population which merits further investigation.

Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014.

During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis.

A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA.

BACKGROUND: Clusters of acute flaccid paralysis or cranial nerve dysfunction in children are uncommon. We aimed to assess a cluster of children with acute flaccid paralysis and cranial nerve dysfunction geographically and temporally associated with an outbreak of enterovirus-D68 respiratory disease. METHODS: We defined a case of neurological disease as any child admitted to Children's Hospital Colorado (Aurora, CO, USA) with acute flaccid paralysis with spinal-cord lesions involving mainly grey matter on imaging, or acute cranial nerve dysfunction with brainstem lesions on imaging, who had onset of neurological symptoms between Aug 1, 2014, and Oct 31, 2014. We used Poisson regression to assess whether the numbers of cases during the outbreak period were significantly greater than baseline case numbers from a historical control period (July 31, 2010, to July 31, 2014). FINDINGS: 12 children met the case definition (median age 11·5 years [IQR 6·75-15]). All had a prodromal febrile illness preceding neurological symptoms by a median of 7 days (IQR 5·75-8). Neurological deficits included flaccid limb weakness (n=10; asymmetric n=7), bulbar weakness (n=6), and cranial nerve VI (n=3) and VII (n=2) dysfunction. Ten (83%) children had confluent, longitudinally extensive spinal-cord lesions of the central grey matter, with predominant anterior horn-cell involvement, and nine (75%) children had brainstem lesions. Ten (91%) of 11 children had cerebrospinal fluid pleocytosis. Nasopharyngeal specimens from eight (73%) of 11 children were positive for rhinovirus or enterovirus. Viruses from five (45%) of 11 children were typed as enterovirus D68. Enterovirus PCR of cerebrospinal fluid, blood, and rectal swabs, and tests for other causes, were negative. Improvement of cranial nerve dysfunction has been noted in three (30%) of ten children. All ten children with limb weakness have residual deficits. INTERPRETATION: We report the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of enterovirus-D68 respiratory illness. Our findings suggest the possibility of an association between enterovirus D68 and neurological disease in children. If enterovirus-D68 infections continue to happen in an endemic or epidemic pattern, development of effective antiviral or immunomodulatory therapies and vaccines should become scientific priorities. FUNDING: National Center for Advancing Translational Sciences, National Institutes of Health.

Enterovirus D68 in Critically Ill Children: A Comparison With Pandemic H1N1 Influenza.

OBJECTIVE: In 2014, the Unites States experienced an outbreak of enterovirus D68 associated with severe respiratory illness. The clinical characteristics associated with severe illness from enterovirus D68 during this outbreak compared with those associated with the 2009 H1N1 influenza virus outbreak are unknown. DESIGN AND SETTING: In this retrospective cohort study, we characterized the clinical features of children with enterovirus D68 admitted to the PICU between August 1, 2014, and November 1, 2014, and compared them with critically ill children infected with H1N1 influenza during the pandemic admitted between May 1, 2009, and January 31, 2010. PATIENTS: PICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-seven severely ill children with enterovirus D68 infections were compared with 68 children infected with H1N1 influenza during the 2009 pandemic. Children with enterovirus D68 were more likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway disease exacerbations, with greater receipt of albuterol (94% vs 49%) and steroids (89% vs 40%; p < 0.0001 for both). Although more children with enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza, they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05 for all). Compared with children with other enteroviruses and rhinoviruses, children with enterovirus D68 were more likely to have a history of asthma (64% vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both). CONCLUSIONS: Critically ill children with enterovirus D68 were more likely to present with reactive airway disease exacerbations, whereas children with H1N1 influenza were more likely to present with pneumonia. Compared with the pandemic H1N1 influenza outbreak, the enterovirus D68 outbreak resulted in more children requiring admission to the ICU, but was associated with less severe outcomes.

Wishful Thinking? Inside the Black Box of Exposure Assessment.

BACKGROUND: Decision-making processes used by experts when undertaking occupational exposure assessment are relatively unknown, but it is often assumed that there is a common underlying method that experts employ. However, differences in training and experience of assessors make it unlikely that one general method for expert assessment would exist. Therefore, there are concerns about formalizing, validating, and comparing expert estimates within and between studies that are difficult, if not impossible, to characterize. Heuristics on the other hand (the processes involved in decision making) have been extensively studied. Heuristics are deployed by everyone as short-cuts to make the often complex process of decision-making simpler, quicker, and less burdensome. Experts' assessments are often subject to various simplifying heuristics as a way to reach a decision in the absence of sufficient data. Therefore, investigating the underlying heuristics or decision-making processes involved may help to shed light on the 'black box' of exposure assessment. METHODS: A mixed method study was conducted utilizing both a web-based exposure assessment exercise incorporating quantitative and semiqualitative elements of data collection, and qualitative semi-structured interviews with exposure assessors. Qualitative data were analyzed using thematic analysis. RESULTS: Twenty-five experts completed the web-based exposure assessment exercise and 8 of these 25 were randomly selected to participate in the follow-up interview. Familiar key themes relating to the exposure assessment exercise emerged; 'intensity'; 'probability'; 'agent'; 'process'; and 'duration' of exposure. However, an important aspect of the detailed follow-up interviews revealed a lack of structure and order with which participants described their decision making. Participants mostly described some form of an iterative process, heavily relying on the anchoring and adjustment heuristic, which differed between experts. CONCLUSION: In spite of having undertaken comparable training (in occupational hygiene or exposure assessment), experts use different methods to assess exposure. Decision making appears to be an iterative process with heavy reliance on the key heuristic of anchoring and adjustment. Using multiple experts to assess exposure while providing some form of anchoring scenario to build from, and additional training in understanding the impact of simple heuristics on the process of decision making, is likely to produce a more methodical approach to assessment; thereby improving consistency and transparency in expert exposure assessment.

Triggering interventions for influenza: the ALERT algorithm.

BACKGROUND: Early, accurate predictions of the onset of influenza season enable targeted implementation of control efforts. Our objective was to develop a tool to assist public health practitioners, researchers, and clinicians in defining the community-level onset of seasonal influenza epidemics. METHODS: Using recent surveillance data on virologically confirmed infections of influenza, we developed the Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm, a method to identify the period of highest seasonal influenza activity. We used data from 2 large hospitals that serve Baltimore, Maryland and Denver, Colorado, and the surrounding geographic areas. The data used by ALERT are routinely collected surveillance data: weekly case counts of laboratory-confirmed influenza A virus. The main outcome is the percentage of prospective seasonal influenza cases identified by the ALERT algorithm. RESULTS: When ALERT thresholds designed to capture 90% of all cases were applied prospectively to the 2011-2012 and 2012-2013 influenza seasons in both hospitals, 71%-91% of all reported cases fell within the ALERT period. CONCLUSIONS: The ALERT algorithm provides a simple, robust, and accurate metric for determining the onset of elevated influenza activity at the community level. This new algorithm provides valuable information that can impact infection prevention recommendations, public health practice, and healthcare delivery.

Epidemiology and clinical characteristics of infants with human parechovirus or human herpes virus-6 detected in cerebrospinal fluid tested for enterovirus or herpes simplex virus.

Human parechovirus (HPeV) and human herpes virus-6 (HHV-6) are acquired commonly in infancy and associated with central nervous system infection. The prevalence of HPeV and HHV-6 in the cerebrospinal fluid (CSF) of infants tested for enterovirus (EV) and herpes-simplex virus (HSV) is unknown. All stored CSF samples from EV or HSV testing in infants less than 6 months of age at Children's Hospital Colorado between January 1, 2010 and December 31, 2011 were tested for HPeV, HHV-6, EV, and HSV by PCR. Clinical characteristics and epidemiological data were collected using retrospective electronic chart review. Of 239 infants tested, 29 cases of EV (12.1%), 7 cases of HPeV (2.9%), 5 cases of HHV-6 (2.1%), and 5 cases of HSV (2.1%) were identified with no bacterial co-infections. HPeV cases occurred between July and October in infants with median age of 24 days. Infants with HPeV had a median maximum temperature of 39 °C, median fever duration of 3 days and median peripheral white blood cell count of 5.2 × 10(3)/µL. HHV-6 cases occurred in infants with median age of 61 days without seasonality. Five percent of infants less than 6 months of age undergoing testing for EV or HSV have HPeV or HHV-6 in the CSF. Targeting testing of HPeV towards febrile infants less than 2 months of age with leukopenia in the late summer to early fall, and HHV-6 towards older infants may increase diagnostic yield. The clinical and fiscal impact of testing infants for HPeV and HHV-6 needs to be determined.

Viral gastroenteritis in children in Colorado 2006-2009.

Acute gastroenteritis accounts for a significant burden of medically attended illness in children under the age of five. For this study, four multiplex reverse transcription PCR assays were used to determine the incidence of adenovirus, astrovirus, coronavirus, norovirus GI and GII, rotavirus, and sapovirus in stool samples submitted for viral electron microscopy (EM) to the Children's Hospital Colorado. Of 1105 stool samples available, viral RNA/DNA was detected in 247 (26.2%) of 941 pediatric samples (median age = 2.97 years, 54% male) with 28 (3.0%) positive for more than one virus. Adenovirus, astrovirus, norovirus GI, norovirus GII, rotavirus, and sapovirus were detected in 95 (10.0%), 33 (3.5%), 8 (0.9%), 90 (9.6%), 49 (5.2%), and 2 (0.2%) of the pediatric samples, respectively. No coronaviruses were identified. Sequencing of norovirus positive samples indicated an outbreak of norovirus strain GII.4 in 2006 with evidence of numerous circulating strains. Multiple samples from the same immunocompromised patients demonstrated symptomatic shedding of norovirus for up to 32 weeks and astrovirus for 12 weeks. RT-PCR detected 99 of 111 (89%) adenovirus-positive samples versus 12 (11%) by EM, and 186 of 192 (97%) sapovirus/astrovirus/norovirus-positive samples versus 21 (11%) by EM. Noroviruses and adenoviruses are common causes of gastroenteritis in children. Immunocompromised patients can be infected with multiple viruses and shed viruses in their stools for prolonged periods. This data support the superiority of RT-PCR compared to EM for diagnosis of viral gastroenteritis.

Pure Immature Teratoma of the Ovary in Adults: Thirty-Year Experience of a Single Tertiary Care Center.

OBJECTIVE: The aim of this study was to evaluate clinicopathologic characteristics, treatment outcome, and reproductive function in women diagnosed with ovarian immature teratoma (IT). Our standard chemotherapy regime is currently etoposide/cisplatin (EP), creating a unique opportunity to evaluate this protocol in ovarian ITs. MATERIALS AND METHODS: This study is a retrospective analysis. Twenty-seven women older than 18 years with ovarian IT stages IA to IIIC were identified and included in this study. Patients were treated at 1 institution, Health Sciences Center, Women's Hospital, Winnipeg, Manitoba, Canada, between 1983 and 2013. RESULTS: The median age at diagnosis was 27.0 years (range, 18-36 years). Twenty-two (82%) presented with an International Federation of Gynecology and Obstetrics stage I disease, 3 (11%) had stage II, and 2 patients (7%) had stage III disease. The histologic grade distribution was grade I in 9 patients (33%), grade II in 3 patients (11%), and grade III in 15 patients (56%). Initial management was surgical for all patients: 3 (11%) hysterectomy and bilateral salpingo-oophorectomy, 1 (4%) cystectomy only, and 23 (85%) unilateral salpingo-oophorectomy. Twenty-one patients (78%) received adjuvant therapy. The median follow-up was 60 months (range, 36-72 months). One patient recurred (histological grade III) 6 months after surgery and had a complete clinical response to 4 cycles of EP chemotherapy. Twelve patients reported an attempt to conceive resulting in 10 pregnancies (8 after chemotherapy). CONCLUSIONS: Ovarian IT is a curable disease. Fertility-sparing surgery should be offered. Adjuvant treatment with cisplatinum-based chemotherapy, typically with bleomycin, etoposide, and cisplatin, is still considered the standard in stages greater than stage IA grade I. Etoposide/cisplatin as a primary chemotherapy regime for early- or advanced-stage disease is an effective treatment with minimal adverse effects and high tolerability. This is the first published study examining EP as a primary treatment modality for IT. Further studies are needed to strengthen these findings.

Agreement of experts and non-experts in a desktop exercise evaluating exposure to asthmagens in the cotton and textile, and other industries.

In the absence of personal exposure measurements, expert assessment, generally on a case-by-case basis, is often used to estimate exposures. However, the decision processes of individual experts when making assessments are unknown, making it difficult to assess the quality of these assessments or to compare different assessments to each other. We conducted a study in primarily the textile and cotton industries, but also in baking, metal work, and agriculture industries in which we assessed agreement between experts assessing intensity and probability of exposure in the absence of exposure measurements to compare how well their performance compares to agreement of non-desktop-based exercises reported in literature. In addition, agreement was compared with that of non-experts undertaking the same exercise, and results were further stratified to assess the impact of factors expected of affected assessments. Intraclass correlation coefficients of absolute agreement (ICC1) and consistency (ICC3) between raters were calculated. Sensitivity and specificity were estimated using a probabilistic simulation methodology developed previously. Fourteen occupational hygienists and exposure assessors with complete data for all 48 job descriptions and 8 non-experts participated. Although confidence intervals about correlation-coefficient differences are not reported, the individual limits were found to be so broad as to suggest that no statistically significant comparisons can be made. Nevertheless, preliminary observations are presented here as suggested by the computed means. Absolute agreement between expert raters was fair-good, but was somewhat better for intensity (ICC1 = 0.61) than for probability (ICC1 = 0.44) of exposure and was better for experts than non-experts. Estimated sensitivity was 0.95 and specificity 0.82 for intensity, and 0.91 and 0.78 for probability of exposure, respectively. Stratification for factors hypothesized to affect agreement did not show statistically significant differences, but consistent patterns of point estimates indicated that agreement between raters (both expert on non-experts) dropped for medium levels of information compared with little or extensive information. Inclusion of a photo or video generally improved agreement between experts but not between non-experts, whereas the year of the job description had no influence on the assessments. These data indicate that the desktop exposure assessment exercise was of similar quality to previously reported levels of agreement. Agreements between experts' assessments were independent of the time period of the job and can be improved by inclusion of visual material. Agreement between experts as well as the non-experts does not increase with the detail of provided job information.

Epidemiology and clinical presentation of parainfluenza type 4 in children: a 3-year comparative study to parainfluenza types 1-3.

BACKGROUND: Human parainfluenza viruses (HPIVs) are among the most common causes of respiratory tract infections in children. Little is known about the epidemiology and clinical presentation of HPIV type 4. METHODS: A retrospective chart review and comparison of patients positive for HPIV types 1-4 by multiplex polymerase chain reaction between 2009 and 2012 at Children's Hospital Colorado was performed. Patients who had only direct fluorescent antibody testing performed or concurrent viral infections were excluded. RESULTS: Of 11,533 samples, 752 (6.5%) were positive for HPIV. After exclusion criteria, 316 samples were included in the study. HPIV-4 had year-round prevalence with biennial peaks in odd-numbered years. HPIV-4 and HPIV-3 had similar clinical presentations. 50.8% and 51.5% of patients with HPIV-3-4 had hypoxia compared to 20.3% and 33.3% of patients with HPIV-1-2 (P < .01). HPIV-1 (23.6%) and HPIV-2 (24.2%) were more associated with stridor than HPIV-3 (6.6%) and HPIV-4 (0%) (P < .01). No patients with HPIV-4 had croup. Patients with HPIV-4 had similar lengths of stay and mortality as those with HPIV-1-3. CONCLUSIONS: This is the first large-scale analysis of HPIV-4 clinical and epidemiologic features. HPIV-4 was most similar to HPIV-3 in clinical presentation. HPIV-4 had year-round prevalence with peaks in the autumn of odd-numbered years. HPIV-4 is a common respiratory pathogen capable of causing significant morbidity in children.

Isolation, propagation, genome analysis and epidemiology of HKU1 betacoronaviruses.

From 1 January 2009 to 31 May 2013, 15 287 respiratory specimens submitted to the Clinical Virology Laboratory at the Children's Hospital Colorado were tested for human coronavirus RNA by reverse transcription-PCR. Human coronaviruses HKU1, OC43, 229E and NL63 co-circulated during each of the respiratory seasons but with significant year-to-year variability, and cumulatively accounted for 7.4-15.6 % of all samples tested during the months of peak activity. A total of 79 (0.5 % prevalence) specimens were positive for human betacoronavirus HKU1 RNA. Genotypes HKU1 A and B were both isolated from clinical specimens and propagated on primary human tracheal-bronchial epithelial cells cultured at the air-liquid interface and were neutralized in vitro by human intravenous immunoglobulin and by polyclonal rabbit antibodies to the spike glycoprotein of HKU1. Phylogenetic analysis of the deduced amino acid sequences of seven full-length genomes of Colorado HKU1 viruses and the spike glycoproteins from four additional HKU1 viruses from Colorado and three from Brazil demonstrated remarkable conservation of these sequences with genotypes circulating in Hong Kong and France. Within genotype A, all but one of the Colorado HKU1 sequences formed a unique subclade defined by three amino acid substitutions (W197F, F613Y and S752F) in the spike glycoprotein and exhibited a unique signature in the acidic tandem repeat in the N-terminal region of the nsp3 subdomain. Elucidating the function of and mechanisms responsible for the formation of these varying tandem repeats will increase our understanding of the replication process and pathogenicity of HKU1 and potentially of other coronaviruses.

Expression, purification, crystallization and preliminary X-ray diffraction analysis of a lactococcal bacteriophage small terminase subunit.

Terminases are enzymes that are required for the insertion of a single viral genome into the interior of a viral procapsid by a process referred to as 'encapsulation or packaging'. Many double-stranded DNA viruses such as bacteriophages T3, T4, T7, λ and SPP1, as well as herpes viruses, utilize terminase enzymes for this purpose. All the terminase enzymes described to date require two subunits, a small subunit referred to as TerS and a large subunit referred to as TerL, for in vivo activity. The TerS and TerL subunits interact with each other to form a functional hetero-oligomeric enzyme complex; however the stoichiometry and oligomeric state have not been determined. We have cloned, expressed and purified recombinant small terminase TerS from a 936 lactococcal bacteriophage strain ASCC454, initially isolated from a dairy factory. The terminase was crystallized using a combination of nanolitre sitting drops and vapour diffusion using sodium malonate as the precipitant, and crystallization optimized using standard vapour-diffusion hanging drops set up in the presence of a nitrogen atmosphere. The crystals belong to the P2 space group, with unit-cell parameters a=73.93, b=158.48, c=74.23 Å, and diffract to 2.42 Šresolution using synchrotron radiation. A self-rotation function calculation revealed that the terminase oligomerizes into an octamer in the asymmetric unit, although size-exclusion chromatography suggests that it is possible for it to form an oligomer of up to 13 subunits.

Comparing barriers and enablers of women's health leadership in India with East Africa and North America.

Background: Women are estimated to hold between 70 and 75% of global health positions worldwide yet persistent inequities in power and leadership remain. There is little information on specific enablers and barriers that women working in public health face in India and how those compare with other regions. Methods: We collected and analyzed information from women working in public health in India and East Africa (Kenya, Rwanda, and Uganda) and in global health (Canada and United States), to understand and document the specific enablers and barriers women face in India, compared with other regions. Findings: Several universal themes emerged around factors enabling (mentors, professional networks, leadership based in empathy and team building) or impeding (obvert bias and family responsibilities) women across all contexts. Within this, there are nuances in how women's leadership growth factors and obstacles play out in India differently than in other contexts. Interpretation: There are important similarities in the enablers and barriers faced by women in India and other geographies and important ways these differs in for women in India. By designing programs and policies at institutional levels to address these factors, we can create a professional ecosystem that works for women in health and beyond. Funding: This research was funded by WomenLift Health, which is funded by the Bill and Melinda Gates Foundation. Representatives from WomenLift Health, listed as authors, participated in the conceptualization of the research to define objectives and core questions, provided commentary and revision to improve the manuscript, and supervised the progress of the research.

Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination.

This study compared the complete genome sequences of 16 NL63 strain human coronaviruses (hCoVs) from respiratory specimens of paediatric patients with respiratory disease in Colorado, USA, and characterized the epidemiology and clinical characteristics associated with circulating NL63 viruses over a 3-year period. From 1 January 2009 to 31 December 2011, 92 of 9380 respiratory specimens were found to be positive for NL63 RNA by PCR, an overall prevalence of 1 %. NL63 viruses were circulating during all 3 years, but there was considerable yearly variation in prevalence and the month of peak incidence. Phylogenetic analysis comparing the genome sequences of the 16 Colorado NL63 viruses with those of the prototypical hCoV-NL63 and three other NL63 viruses from the Netherlands demonstrated that there were three genotypes (A, B and C) circulating in Colorado from 2005 to 2010, and evidence of recombination between virus strains was found. Genotypes B and C co-circulated in Colorado in 2005, 2009 and 2010, but genotype A circulated only in 2005 when it was the predominant NL63 strain. Genotype C represents a new lineage that has not been described previously. The greatest variability in the NL63 virus genomes was found in the N-terminal domain (NTD) of the spike gene (nt 1-600, aa 1-200). Ten different amino acid sequences were found in the NTD of the spike protein among these NL63 strains and the 75 partial published sequences of NTDs from strains found at different times throughout the world.