Approximating Nearest Neighbor Distances

Several researchers proposed using non-Euclidean metrics on point sets in Euclidean space for clustering noisy data. Almost always, a distance function is desired that recognizes the closeness of the points in the same cluster, even if the Euclidean cluster diameter is large. Therefore, it is preferred to assign smaller costs to the paths that stay close to the input points. In this paper, we consider the most natural metric with this property, which we call the nearest neighbor metric. Given a point set P and a path $\gamma$, our metric charges each point of $\gamma$ with its distance to P. The total charge along $\gamma$ determines its nearest neighbor length, which is formally defined as the integral of the distance to the input points along the curve. We describe a $(3+\varepsilon)$-approximation algorithm and a $(1+\varepsilon)$-approximation algorithm to compute the nearest neighbor metric. Both approximation algorithms work in near-linear time. The former uses shortest paths on a sparse graph using only the input points. The latter uses a sparse sample of the ambient space, to find good approximate geodesic paths.Comment: corrected author nam

A Class of Eccentric Binaries with Dynamic Tidal Distortions Discovered with Kepler

We have discovered a class of eccentric binary systems within the Kepler data archive that have dynamic tidal distortions and tidally-induced pulsations. Each has a uniquely shaped light curve that is characterized by periodic brightening or variability at time scales of 4-20 days, frequently accompanied by shorter period oscillations. We can explain the dominant features of the entire class with orbitally-varying tidal forces that occur in close, eccentric binary systems. The large variety of light curve shapes arises from viewing systems at different angles. This hypothesis is supported by spectroscopic radial velocity measurements for five systems, each showing evidence of being in an eccentric binary system. Prior to the discovery of these 17 new systems, only four stars, where KOI-54 is the best example, were known to have evidence of these dynamic tides and tidally-induced oscillations. We perform preliminary fits to the light curves and radial velocity data, present the overall properties of this class and discuss the work required to accurately model these systems.Comment: 13 pages, submitted to Ap

Genetic Analysis of a Novel Human Adenovirus with a Serologically Unique Hexon and a Recombinant Fiber Gene

In February of 1996 a human adenovirus (formerly known as Ad-Cor-96-487) was isolated from the stool of an AIDS patient who presented with severe chronic diarrhea. To characterize this apparently novel pathogen of potential public health significance, the complete genome of this adenovirus was sequenced to elucidate its origin. Bioinformatic and phylogenetic analyses of this genome demonstrate that this virus, heretofore referred to as HAdV-D58, contains a novel hexon gene as well as a recombinant fiber gene. In addition, serological analysis demonstrated that HAdV-D58 has a different neutralization profile than all previously characterized HAdVs. Bootscan analysis of the HAdV-D58 fiber gene strongly suggests one recombination event

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome

IMPORTANCE: Patients with atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson’s disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes, but have not been prospectively studied. OBJECTIVE: To define the distinguishing features of PSP and CBS, and to assess their usefulness in facilitating early diagnosis and separation from PD. DESIGN, SETTING, PARTICIPANTS: Cohort study which recruited APS and PD patients from movement disorder clinics across the UK from September 2015 to December 2018, and will follow up patients over 5 years. APS patients were stratified into PSP-Richardson syndrome, PSP-subcortical (including PSP-parkinsonism and PSP-progressive gait freezing cases), PSP-cortical (including PSP-frontal and PSP/CBS overlap cases), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer’s and CBS-non-Alzheimer’s groups. MAIN OUTCOME MEASURES: Baseline group comparisons were conducted using: 1) Clinical trajectory; 2) Cognitive screening scales; 3) Serum neurofilament light chain (NF-L); 4) TRIM11, ApoE and MAPT genotypes; 5) Volumetric MRI. RESULTS: 222 APS cases (101 PSP, 55 MSA, 40 CBS and 26 indeterminate) were recruited (58% male; mean age at recruitment, 68.3 years). Age-matched controls (n=76) and PD cases (n=1967) were also included. Concordance between the ante-mortem clinical diagnosis and pathological diagnosis was achieved in 12/13 (92%) of PSP and CBS cases coming to post-mortem. Applying the MDS PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP. 49/101 (49%) of reclassified PSP patients did not have classical PSP-Richardson syndrome. PSP-subcortical patients had a longer diagnostic latency and a more benign clinical trajectory than PSP-Richardson syndrome and PSP-cortical (p<0.05). PSP-subcortical was distinguished from PSP-cortical and PSP-Richardson syndrome by cortical volumetric MRI measures (AUC 0.84-0.89), cognitive profile (AUC 0.80-0.83), serum NF-L (AUC 0.75-0.83) and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP subtypes. 8/17 (47%) of CBS patients with CSF analysis were identified as having CBS-Alzheimer’s. CBS-Alzheimer’s patients had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment and higher APOE-ε4 allele frequency than CBS-non-Alzheimer’s (p<0.05, AUC 0.80-0.87). Serum NF-L levels distinguished PD from PSP and CBS (p<0.05, AUC 0.80). CONCLUSIONS AND RELEVANCE: Clinical, therapeutic and epidemiological studies focusing on PSP-Richardson syndrome are likely to miss a large number of patients with underlying PSP-tau pathology. CSF analysis defines a distinct CBS-Alzheimer’s subgroup. PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis

Computational and Serologic Analysis of Novel and Known Viruses in Species Human Adenovirus D in Which Serology and Genomics Do Not Correlate

In November of 2007 a human adenovirus (HAdV) was isolated from a bronchoalveolar lavage (BAL) sample recovered from a biopsy of an AIDS patient who presented with fever, cough, tachycardia, and expiratory wheezes. To better understand the isolated virus, the genome was sequenced and analyzed using bioinformatic and phylogenomic analysis. The results suggest that this novel virus, which is provisionally named HAdV-D59, may have been created from multiple recombination events. Specifically, the penton, hexon, and fiber genes have high nucleotide identity to HAdV-D19C, HAdV-D25, and HAdV-D56, respectively. Serological results demonstrated that HAdV-D59 has a neutralization profile that is similar yet not identical to that of HAdV-D25. Furthermore, we observed a two-fold difference between the ability of HAdV-D15 and HAdV-D25 to be neutralized by reciprocal antiserum indicating that the two hexon proteins may be more similar in epitopic conformation than previously assumed. In contrast, hexon loops 1 and 2 of HAdV-D15 and HAdV-D25 share 79.13 and 92.56 percent nucleotide identity, respectively. These data suggest that serology and genomics do not always correlate

Properly Folded Bacterially Expressed H1N1 Hemagglutinin Globular Head and Ectodomain Vaccines Protect Ferrets against H1N1 Pandemic Influenza Virus

Background: In the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is the most effective approach to prevent the large scale mortality and morbidity that was associated with the 1918 "Spanish Flu". The traditional process of influenza vaccine production in eggs is time consuming and may not meet the demands of rapid global vaccination required to curtail influenza pandemic. Methodology/Principal Findings: Recombinant technology can be used to express the hemagglutinin (HA) of the emerging new influenza strain in a variety of systems including mammalian, insect, and bacterial cells. In this study, two forms of HA proteins derived from the currently circulating novel H1N1 A/California/07/2009 virus, HA1 (1-330) and HA (1- 480), were expressed and purified from E. coli under controlled redox refolding conditions that favoured proper protein folding. However, only the recombinant HA1 (1-330) protein formed oligomers, including functional trimers that bound receptor and caused agglutination of human red blood cells. These proteins were used to vaccinate ferrets prior to challenge with the A/California/07/2009 virus. Both proteins induced neutralizing antibodies, and reduced viral loads in nasal washes. However, the HA1 (1-330) protein that had higher content of multimeric forms provided better protection from fever and weight loss at a lower vaccine dose compared with HA (1-480). Protein yield for the HA1 (1-330) ranged around 40 mg/Liter, while the HA (1-480) yield was 0.4-0.8 mg/Liter. Conclusions/Significance: This is the first study that describes production in bacterial system of properly folded functional globular HA1 domain trimers, lacking the HA2 transmembrane protein, that elicit potent neutralizing antibody responses following vaccination and protect ferrets from in vivo challenge. The combination of bacterial expression system with established quality control methods could provide a mechanism for rapid large scale production of influenza vaccines in the face of influenza pandemic threat

Road Trauma in Teenage Male Youth with Childhood Disruptive Behavior Disorders: A Population Based Analysis

Donald Redelmeier and colleagues conducted a population-based case-control study of 16-19-year-old males hospitalized for road trauma or appendicitis and showed that disruptive behavior disorders explained a significant amount of road trauma in this group

Kepler Mission Design, Realized Photometric Performance, and Early Science

The Kepler Mission, launched on Mar 6, 2009 was designed with the explicit capability to detect Earth-size planets in the habitable zone of solar-like stars using the transit photometry method. Results from just forty-three days of data along with ground-based follow-up observations have identified five new transiting planets with measurements of their masses, radii, and orbital periods. Many aspects of stellar astrophysics also benefit from the unique, precise, extended and nearly continuous data set for a large number and variety of stars. Early results for classical variables and eclipsing stars show great promise. To fully understand the methodology, processes and eventually the results from the mission, we present the underlying rationale that ultimately led to the flight and ground system designs used to achieve the exquisite photometric performance. As an example of the initial photometric results, we present variability measurements that can be used to distinguish dwarf stars from red giants.Comment: 16 pages, 5 figures, 1 table 26 Jan revision replaced Subject headings with keywords from approved lis

Extracranial germ cell tumours : mature and immature (1990–2015). First report by the South African Association of Paediatric Haematology Oncology (SAAPHO)

DATA AVAILABILITY STATEMENT : Data restricted due to ethical considerations, but reasonable requests will be considered by the corresponding author and only with the express consent of the South African Association of Paediatric Haematology Oncology (SAAPHO).BACKGROUND AND OBJECTIVES : Outcomes of rare paediatric teratomas have not previously been reported nor treatment regimens standardised in low- and middle-income settings. We sought to evaluate treatment outcomes of children and adolescents with histologically confirmed extracranial germ cell tumours, both mature teratomas (MT) and immature teratomas (IT) in preparation for the development of the South African national treatment guideline. METHODS : Retrospective data by folder review were collated from nine South African paediatric oncology units. Kaplan–Meier analysis with Cox regression was performed to determine 5-year overall survival (OS) and prognostic factors. RESULTS : From January 1990 to December 2015, 60 patients were diagnosed with MTs; 14 males (median age 2 months; interquartile range [IQR]: 0–8.75 months) and 46 females (median age 9 months; IQR: 0–88.5 months). Forty patients were diagnosed with ITs; 10 males (median age less than 1 month; IQR: 0–1.75 months) and 30 females (median age 4.5 months; IQR: 1–162 months). There were high rates of upfront surgical resections in patients with MTs (58/60; 96.6%) and ITs (36/40; 90%), and similarly satisfactory rates of complete resection in patients with both MTs (55/60; 91.7%) and ITs (32/40; 80%). The 5-year OS for the whole group was 85.4%, significantly influenced by stage: Stage I (96.9%), Stage II (100%), Stage III (38.9%) (p < .001 [MT]; p = .013 [IT]). The event-free survival (EFS) ratio for the whole cohort was 78.7%. CONCLUSIONS : Five-year OS for those with low-stage disease was excellent, but was poorer for patients with advanced disease. The implementation of a national treatment guideline will facilitate the standardising of surgical approaches, indications for chemotherapy and specifications for follow-up to improve survival and to collect more robust late effects data.The National Research foundation; Harry Crossley Foundation and Professor Bongani Mayosi Netcare Clinical Scholarship.https://wileyonlinelibrary.com/journal/pbchj2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein