Chronic Underfit of the Small Firm’s HRM Function: When Low Functional Elaboration Interacts with Contingencies

We address qualitative functional elaboration of human resource management (HRM) in small firms where HRM is typically simple and informal. After describing qualitative functional elaboration in terms of structuration, managerial process, and effects on HRM, we discuss relevant contingencies that can render small-firm HRM’s degree of elaboration insufficient relative to firm needs and goals. We then discuss implications of chronic underfit of HRM in small firms, drawing on theory of asymmetric effects of misfit. Finally, we discuss implications for future research, practice, and entrepreneurship education

On Antecedents of Functional Elaboration of HRM in Small Firms

This work further develops the foundation for a functional elaboration theory of human resource management (HRM) in small firms (Wilkerson & Seers, 2019) by detailing some antecedents of HRM’s qualitative and quantitative elaboration in the small firm. Whereas theoretical development in this area to date has focused on functional elaboration and associated fit or misfit of HRM to relevant contingencies, adequate explanation of antecedents has been lacking. We present propositions regarding several entrepreneurial and organizational predictors of, as well as relevant interactive effects on, HRM’s functional elaboration in small firms

Development of a liquid chromatography tandem mass spectrometry method for the simultaneous measurement of voriconazole, posaconazole and itraconazole

Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20  µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3  µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R2 = 0.995) and 5 mg/L for posaconazole (R2 = 0.990) and itraconazole (R2 = 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring. </jats:sec

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin) : study protocol for a randomized controlled trial

Peer reviewedPublisher PD

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

On the Origin of Near-Infrared Extragalactic Background Light Anisotropy

Extragalactic background light (EBL) anisotropy traces variations in the total production of photons over cosmic history, and may contain faint, extended components missed in galaxy point source surveys. Infrared EBL fluctuations have been attributed to primordial galaxies and black holes at the epoch of reionization (EOR), or alternately, intra-halo light (IHL) from stars tidally stripped from their parent galaxies at low redshift. We report new EBL anisotropy measurements from a specialized sounding rocket experiment at 1.1 and 1.6 micrometers. The observed fluctuations exceed the amplitude from known galaxy populations, are inconsistent with EOR galaxies and black holes, and are largely explained by IHL emission. The measured fluctuations are associated with an EBL intensity that is comparable to the background from known galaxies measured through number counts, and therefore a substantial contribution to the energy contained in photons in the cosmos.Comment: 65 pages, 29 figures, Published in Science Nov 7 2014 (includes supplementary material

Development of a CHO production medium utilizing proteomic and metabolomics analysis

productivity. Metabolomics and proteomic analysis was conducted on two medium formulations with disparate growth and production characteristics. Medium formulation 1 (M1) demonstrates moderate peak VCD with a high specific productivity (qP) over a 14 day growth performance assay utilizing a recombinant IgG producing CHO-S cell line and DG44 cell line. Medium formulation 2 (M2) demonstrates a high peak VCD with moderate qP under the same conditions and cell line. A comparative analysis of metabolite abundance and enzyme regulation identified that M1 had greater flux in the sorbitol pathway verses glycolysis, the TCA cycle was upregulated to a greater degree than M2. A Design of Experiment (DoE) study was developed to increase the specific productivity of M1 without decreasing the VCD to M2 levels resulting in a superior volumetric titer. Simultaneously, we utilized traditional empirical approaches to increase the qP of M2 in a parallel set of experiments. We describe here the path to develop the medium, metabolic and proteomic pathways which were found to be important, and a comparison of results based on the traditional empirical path verses the hypothesis based advanced cellular analytics path

Buffered 1% Lidocaine With Epinephrine Can Be as Effective as Nonbuffered 2% Lidocaine With Epinephrine for Maxillary Field Block

Buffering local anesthetics with epinephrine (Epi) offers clinicians options not often considered. This study assessed outcomes for pulpal anesthesia, pain on injection, and time to midface numbness for buffered 1% lidocaine with 1:100,000 Epi versus nonbuffered 2% lidocaine with 1:100,000 Epi. In this trial with a randomized, crossover design, buffered 1% lidocaine was compared with nonbuffered 2% lidocaine. Subjects were adult volunteers who served as their own controls. The predictor variables were alternate drug formulations. The outcome variables were subjects' responses to cold and electric pulp testing (EPT) stimulation of the maxillary first molar and canine, pain levels during the injection, and time to midface numbness. After maxillary field blocks with 40 mg of buffered lidocaine or 80 mg of nonbuffered lidocaine, subjects reported pain on injection and responses of the maxillary first molar and canine after cold and EPT stimulation. Teeth were tested before field block and at 30-minute intervals until a positive response was detected. Two weeks later, subjects were tested with the alternate drug combinations. For all outcome variables, assessment of treatment difference, calculated as 1% buffered minus 2% nonbuffered, was performed with the Wilcoxon rank sum test with significance at P < .05. More of the 24 subjects were women and Caucasian. The median age was 23.5 years (interquartile range, 21, 25 years), and the median body weight was 155 lb (interquartile range, 128.5, 176.5 lb). Pain levels during the injection were significantly lower for 1% buffered lidocaine, with P = .04. Times to response after injection were not significantly different between the 2 drug formulations for the cold test on a molar, with P = .08, or the cold test on a canine, with P = .22. However, times to response were significantly longer for nonbuffered drugs for EPT on the molar and canine, both with P = .01. Buffering 1% lidocaine with 1:100,000 Epi reduces the pain on injection with a maxillary field block and results in similar lengths of pulpal anesthesia tested with a cold stimulus as compared with nonbuffered 2% lidocaine with 1:100,000 Epi

Safe and just operating spaces for regional social-ecological systems

Humanity faces a major global challenge in achieving wellbeing for all, while simultaneously ensuring that the biophysical processes and ecosystem services that underpin wellbeing are exploited within scientifically informed boundaries of sustainability. We propose a framework for defining the safe and just operating space for humanity that integrates social wellbeing into the original planetary boundaries concept (Rockström et al., 2009a,b) for application at regional scales. We argue that such a framework can: (1) increase the policy impact of the boundaries concept as most governance takes place at the regional rather than planetary scale; (2) contribute to the understanding and dissemination of complexity thinking throughout governance and policy-making; (3) act as a powerful metaphor and communication tool for regional equity and sustainability. We demonstrate the approach in two rural Chinese localities where we define the safe and just operating space that lies between an environmental ceiling and a social foundation from analysis of time series drawn from monitored and palaeoecological data, and from social survey statistics respectively. Agricultural intensification has led to poverty reduction, though not eradicated it, but at the expense of environmental degradation. Currently, the environmental ceiling is exceeded for degraded water quality at both localities even though the least well-met social standards are for available piped water and sanitation. The conjunction of these social needs and environmental constraints around the issue of water access and quality illustrates the broader value of the safe and just operating space approach for sustainable development