Contributions to the theory of neighborhoods and its applications

Neighborhoods have played a fundamental role in general topology since the birth of the field. This work outlines the historial evolution of the notion of neighborhood and employs neighborhood assignments, weak neighborhood assignments, and a naturally induced notion of duality in a study of non-Hausdorff topological spaces. Neighborhood characterizations of various classes of spaces, among them the developable and the pseudometrizable spaces, are obtained. A generalization of topological spaces based upon a primitive notion of neighborhood is explored and examples are supplied to motivate the investigation

Employment Relations in the New Zealand Public Health Sector - A Survey

The New Zealand Public Health sector has undergone significant political, Legislative and managerial changes since 1986. These changes have had a major impact on the nature of employment relations in the sector. The unified, state sector industrial relations regime has been restructured and replaced a by diverse set of practices. Many of the changes of the last decade have had time to 'mature' and become embedded into the system and it now seems appropriate to start to identify issues that have arisen from the impact of the new regime of employment relations. This paper presents the results of a survey of related public health sector organisations including employers, unions, professional organisations, statutory bodies and funding agencies. Five distinct areas for future employment relations research, with varying Levels of priority, were identified by the respondents including; 1) Workforce development and planning. 2) The nature, scope and negotiation of employment contracts. 3) The problematic of people management of largely 'professional ' group of workers. 4) Relationships with external organisations such as the 'NZQA 'and the 'Health and Disability Commissioner' and the impact on internal employment relations. 5) The effects of uncertainty about current health care delivery structures and possible further politically directed restructuring are having on employment relations

Employment Relations in the New Zealand Public Health Sector - A Survey

The New Zealand Public Health sector has undergone significant political, Legislative and managerial changes since 1986. These changes have had a major impact on the nature of employment relations in the sector. The unified, state sector industrial relations regime has been restructured and replaced a by diverse set of practices. Many of the changes of the last decade have had time to 'mature' and become embedded into the system and it now seems appropriate to start to identify issues that have arisen from the impact of the new regime of employment relations. This paper presents the results of a survey of related public health sector organisations including employers, unions, professional organisations, statutory bodies and funding agencies. Five distinct areas for future employment relations research, with varying Levels of priority, were identified by the respondents including; 1) Workforce development and planning. 2) The nature, scope and negotiation of employment contracts. 3) The problematic of people management of largely 'professional ' group of workers. 4) Relationships with external organisations such as the 'NZQA 'and the 'Health and Disability Commissioner' and the impact on internal employment relations. 5) The effects of uncertainty about current health care delivery structures and possible further politically directed restructuring are having on employment relations

Desired clearance around a vehicle while parking or performing low speed maneuvers

AVM and Low Speed Maneuvers: Human Factors Issues ProjectThis experiment examined how close to objects (such as a wall or another vehicle) people would drive when parking. The findings will to be used as a basis for visual and/or auditory warnings provided by parking assistance systems. A total of 16 people (8 ages 18-30, 8 over age 65) served as subjects. Data were collected both for the subjects sitting in the driver’s seat of a 2004 Infinity Q45 and standing outside the vehicle (as if directing someone else to park). Data were collected for the desired clearance distance between the test vehicle and a wall (for safety concerns, the wall was moved instead of the vehicle) in ascending and descending thresholds, for 8 cardinal clock positions. The overall mean distance was 20.4 in for the 640 data points collected, with a range of 2.5 to 48.5 in. As an example of the specific results, when the wall was moved towards the driver and the subject was an observer (outside the car), the desired distances were 17.0, 18.9, 19.1, 20.3, 17.4, 18.7, 14.7, and 15.8 in for 1:30, 3:00, 4:30, 6:00, 7:30, 9:00, 10:30 and 12:00 clock positions. Using the regression method, 1 of the 2 methods developed, desired distance in inches was equal to 9.5 + 1.6 (if the position was to the side or rear) + 6.7 (if a door was to be opened) + 5.7 (if the object was approaching the car) + 4.9 (if the driver’s clearance was estimated) + .07 times the driver’s age.Nissan Research Centerhttp://deepblue.lib.umich.edu/bitstream/2027.42/64471/1/102435.pd

Alternative images for perpendicular parking: a usability study of a multi-camera parking assistance system

AVM and Low Speed Maneuvers: Human Factors Issues ProjectThe parking assistance system evaluated consisted of four outward facing cameras whose images could be presented on a monitor on the center console. The images presented varied in the location of the virtual eye point of the camera (the height above the vehicle and forward depression angle) and the number of camera images (one or multiple) appearing together. In the experiment, 16 drivers (eight under age 30, eight over age 65) parked a 2002 Infiniti Q45 in an 8.5-foot-wide stall. Each subject parked 24 times, using the various image combinations or no assistance at all. Parking clearances (the closest approach distance on the driver and passenger side, distance to a wall in front) declined with practice, stabilizing to 4 inches laterally and 13 inches in front after about three unrecorded practice trials and 15 test trials. Overall, age and sex differences were not large, though older drivers were more variable than younger drivers in how far they parked from the end of a stall. Finally, there were no statistically significant differences among camera image combinations, or differences from no-assistance conditions. Only half of the subjects made significant use of the assistance system, which is not an unusual outcome given its early state of system development. Of the image combinations examined, those with a single image field resulted in subjects parking 2 inches closer to the wall than those with multiple fields. Overall, subjects preferred scenes presenting what appeared to be a single image. Subjects reported that the aerial view was the most helpful.Nissan Research Centerhttp://deepblue.lib.umich.edu/bitstream/2027.42/64470/1/102434.pd

Binding of C4b-binding protein: A molecular mechanism of serum resistance of Neisseria gonorrhoeae

We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-binding protein (C4bp). Microbial surface-bound C4bp demonstrated cofactor activity. We constructed gonococcal strains with hybrid porin (Por) molecules derived from each of the major serogroups (Por1A and Por1B) of N. gonorrhoeae, and showed that the loop 1 of Por1A is required for C4bp binding. Por1B loops 5 and 7 of serum-resistant gonococci together formed a negatively charged C4bp-binding domain. C4bp-Por1B interactions were ionic in nature (inhibited by high salt or by heparin), whereas the C4bp-Por1A bond was hydrophobic. Only recombinant C4bp mutant molecules containing the NH2-terminal alpha-chain short consensus repeat (SCR1) bound to both Por1A and Por1B gonococci, suggesting that SCR1 contained Por binding sites. C4bp alpha-chain monomers did not bind gonococci, indicating that the polymeric form of C4bp was required for binding. Using fAb fragments against C4bp SCR1, C4bp binding to Por1A and Por1B strains was inhibited in a complement-dependent serum bactericidal assay. This resulted in complete killing of these otherwise fully serum resistant strains in only 10% normal serum, underscoring the importance of C4bp in mediating gonococcal serum resistance

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.Cancer Research UK Clinician Scientist Fellowship C53779/A20097 (M.L.B), Leukaemia Foundation Australia Senior Fellowship and Howard Hughes Medical Institute International Research Scholarship 55008729 (M.A.D), Peter and Julie Alston Centenary fellowship (K.D.S.), Wellcome Trust Principal Research Fellowship 101835/Z/13/Z (P.J.L), Peter MacCallum Postgraduate Scholarship (C.E.S), NHMRC Postgraduate Scholarship (K.L.C.), Maddie Riewoldt's Vision 064728 (Y-C.C), Victorian Cancer Agency (E.Y.N.L), CSL Centenary fellowship (S-J.D), National Breast Cancer Foundation Fellowship ECF-17-005 (P.A.B.), Addenbrooke’s Charitable Trust and NIHR Cambridge BRC (M.L.B., P.J.L), NHMRC grant 1085015, 1106444 (M.A.D) and 1128984 (M.A.D, S-J.D)

BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers.

Endomembrane organelle maturation requires cargo delivery via fusion with membrane transport intermediates and recycling of fusion factors to their sites of origin. Melanosomes and other lysosome-related organelles obtain cargoes from early endosomes, but the fusion machinery involved and its recycling pathway are unknown. Here, we show that the v-SNARE VAMP7 mediates fusion of melanosomes with tubular transport carriers that also carry the cargo protein TYRP1 and that require BLOC-1 for their formation. Using live-cell imaging, we identify a pathway for VAMP7 recycling from melanosomes that employs distinct tubular carriers. The recycling carriers also harbor the VAMP7-binding scaffold protein VARP and the tissue-restricted Rab GTPase RAB38. Recycling carrier formation is dependent on the RAB38 exchange factor BLOC-3. Our data suggest that VAMP7 mediates fusion of BLOC-1-dependent transport carriers with melanosomes, illuminate SNARE recycling from melanosomes as a critical BLOC-3-dependent step, and likely explain the distinct hypopigmentation phenotypes associated with BLOC-1 and BLOC-3 deficiency in Hermansky-Pudlak syndrome variants.This work was supported by grants from the National Institutes of Health, National Eye Institute (R01 EY015625, to M.S. Marks and G.  Raposo), National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR048155, to M.S. Marks, and F32 AR062476, to M.K. Dennis), National Institute of General Medical Sciences (R01 GM108807, to M.S. Marks); Fondation pour la Recherche Médicale (to T.  Galli); the UK Medical Research Council (G0900113, to J.P. Luzio); and the Wellcome Trust (108429, to E.V. Sviderskaya and D.C. Bennett). This work was also supported by a Canadian Institutes of Health Research Fellowship (to G.G.  Hesketh) and a Fondation pour la Recherche Médicale grant from Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut Curie, and Fondation pour la Recherche Médicale (DEQ20140329491 Team label, to G. Raposo).This is the final version of the article. It first appeared from Rockefeller University Press via http://dx.doi.org/10.1083/jcb.20160509

Quality standards in polycentric systems : a case of shipping

This article contributes to the literature on transnational environmental governance (TEG). Polycentricity is a popular conceptual approach in TEG, but coordination in polycentric systems remains largely unexplored. We put forward a conceptual model of quality standards as a productive links between different orders of governance in polycentric systems. Existing theories distinguish between regulative, institutional, and normalizing functioning of quality standards. We develop an integrative approach highlighting the mechanisms of coordination that rely on these three functions of quality standards. The case of TEG in shipping is used to illustrate how quality standards function not only as soft rules, but also as institutionalized references and shared conventions, enabling coordination across levels and scales. The paper draws attention to the limits of regulatory standardization, outlining how practical value can be gained from emphasizing the normative work associated with promulgation of quality standards.Peer reviewe

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients