Simulating the low-temperature, metastable electrochromism of Photosystem I: Applications to Thermosynechococcus vulcanus and Chroococcidiopsis thermalis.

Low-temperature, metastable electrochromism has been used as a tool to assign pigments in Photosystem I (PS I) from Thermosynechococcus vulcanus and both the white light and far-red light (FRL) forms of Chroococcidiopsis thermalis. We find that a minimum of seven pigments is required to satisfactorily model the electrochromism of PS I. Using our model, we provide a short list of candidates for the chlorophyll f pigment in FRL C. thermalis that absorbs at 756 nm, whose identity, to date, has proven to be controversial. Specifically, we propose the linker pigments A40 and B39 and two antenna pigments A26 and B24 as defined by crystal structure 1JB0. The pros and cons of these assignments are discussed, and we propose further experiments to better understand the functioning of FRL C. thermalis.

Rothia aeria vertebral discitis/osteomyelitis in an immunocompetent adult: Case report and literature review.

Rothia aeria is a gram-positive, pleomorphic bacteria forming part of human oral microflora usually only causing periodontal and dental infections. We describe the case of a 68-year-old immunocompetent male with lumbar vertebral discitis/osteomyelitis caused by R. aeria. A review of the literature demonstrated seventeen cases of non-dental R. aeria infection of which only six were in immunocompetent individuals. This is the first reported case of R. aeria vertebral discitis/osteomyelitis.

Tobramycin pharmacokinetics in patients with cystic fibrosis before and after bilateral lung transplantation.

STUDY OBJECTIVES: To compare the pharmacokinetics (PK) of tobramycin in patients with cystic fibrosis (CF) before and after bilateral lung transplantation, in order to evaluate optimal dosing practices post transplant. DESIGN: Retrospective, single-center, chart review study, in which tobramycin concentrations from CF patients were used to calculate PK parameters, including elimination rate constant, half-life, volume of distribution (Vd), area under the curve (AUC), and clearance before and after lung transplantation. SETTING: Medical school-affiliated teaching hospital. PATIENTS: Eight patients with CF, who received a bilateral lung transplant from January 1, 2005 through August 1, 2009 (4 males, 4 females; mean age 26.3 years). INTERVENTIONS: None. MAIN RESULTS: Sixty-nine sets of pre- (n=52) and post transplant (n=17) tobramycin concentrations were available. PK parameters were significantly altered post transplant. Elimination rate constant decreased 38% from 0.26±0.1 to 0.16±0.1 h(-1) (P<0.001), with a related increase of 200% in half-life from 2.8±0.8 to 8.4±8.7 h (P<0.001). Clearance decreased 25% post transplant from 67.3±32.3 to 50.2±15.9 mL/min (P=0.04). No statistically significant change occurred in AUC or Vd after transplant, although a trend was seen toward increased Vd. Dosage requirements after transplantation were significantly lower, 10.7±2.5 and 7.6±1.6 mg/kg/day, pre and post transplant, respectively (P<0.001). Concentrations were also evaluated in 2 time periods: 0-3 weeks and ≥6 weeks post transplant, based on available data. Clearance and Vd ≥6 weeks post transplant did not significantly differ from pre-transplant values (P=0.28 and 0.54, respectively), suggesting that these changes may be temporary. CONCLUSIONS: The results suggest that tobramycin PK are altered in patients with CF after bilateral lung transplantation, although no clear trend was seen owing to inter-patient variability. We propose that PK parameters should be reassessed during each treatment course post transplant.

Establishment of the hemlock woolly adelgid predator, Laricobius nigrinus (Coleoptera: Derodontidae), in the Eastern United States.

The hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae), native to western North America and Asia, was accidentally introduced from Japan to the eastern United States. To potentially establish biological control of A. tsugae, we released a predator endemic to western North America, Laricobius nigrinus Fender (Coleoptera: Derodontidae), from 2003 to 2005, in 22 localities from Georgia to Massachusetts. Release sites spanned the invasive range of the adelgid across five United States Department of Agriculture plant hardiness zones (5a to 7a). Release sizes were 75, 150, 300, 600, or 1,200 adult L. nigrinus per site in the fall, winter, early spring, or sequentially (i.e., fall or winter and early spring). We monitored establishment by annual sampling for L. nigrinus adults with beat sheets and for L. nigrinus larvae by branch clipping. At the end of 3 yr, L. nigrinus was established in 13 of the 22 sites. The following variables were evaluated for their correlation with the numbers of L. nigrinus larvae and adults recovered and for their effect on establishment (scored as F(3) presence/absence): (1) Minimum winter temperature at the release site, (2) A. tsugae density at the time of release, (3) release size, and (4) release season. Only minimum winter temperature was correlated with larval recoveries and no variables were correlated with adult recoveries. Logistic regression modeling found that establishment was positively related to minimum winter temperature and release size. We recommend smaller release sizes in warm areas where establishment probability was high (i.e., zones 7a, 6b, and 6a) and larger release sizes in cold areas where establishment probability was low (i.e., zones 5b and 5a). Releases during fall-early spring and across the range of A. tsugae densities tested were successful.

Contributions of neuroimaging, balance testing, electrophysiology and blood markers to the assessment of sport-related concussion.

OBJECTIVE: To review the diagnostic tests and investigations used in the management of sports concussion, in the adult and paediatric populations, to (a) monitor the severity of symptoms and deficits, (b) track recovery and (c) advance knowledge relating to the natural history and neurobiology of the injury. DESIGN: Qualitative literature review of the neuroimaging, balance testing, electrophysiology, blood marker and concussion literature. INTERVENTION: PubMed and Medline databases were reviewed for investigations used in the management of adult and paediatric concussion, including structural imaging (computerised tomography, magnetic resonance imaging, diffusion tensor imaging), functional imaging (single photon emission computerised tomography, positron emission tomography, functional magnetic resonance imaging), spectroscopy (magnetic resonance spectroscopy, near infrared spectroscopy), balance testing (Balance Error Scoring System, Sensory Organization Test, gait testing, virtual reality), electrophysiological tests (electroencephalography, evoked potentials, event related potentials, magnetoencephalography, heart rate variability), genetics (apolipoprotein E4, channelopathies) and blood markers (S100, neuron-specific enolase, cleaved Tau protein, glutamate). RESULTS: For the adult and paediatric populations, each test has been classified as being: (1) clinically useful, (2) a research tool only or (3) not useful in sports-related concussion. CONCLUSIONS: The current status of the diagnostic tests and investigations is analysed, and potential directions for future research are provided. Currently, all tests and investigations, with the exception of clinical balance testing, remain experimental. There is accumulating research, however, that shows promise for the future clinical application of functional magnetic resonance imaging in sport concussion assessment and management.

Changes in von Willebrand factor and fibrinolysis following a post-exercise cool-down.

The purpose of this study was to determine the effect of a post-exercise active cool-down on von Willebrand factor and fibrinolysis. Ten subjects performed two maximal oxygen uptake (VO2max) tests followed by a 10-min passive (PC) or an active (AC) cool-down. Blood samples were obtained pre-exercise, post-exercise, post-PC/AC, and 1 h post-exercise and analyzed for von Willebrand factor antigen (vWf:Ag), tissue plasminogen activator (tPA) antigen and activity and plasminogen activator inhibitor-1 (PAI-1) activity. Data were analyzed using repeated measures analysis of variance. No significant differences were found between VO2max tests for treadmill time, VO2max, respiratory exchange ratio, maximal heart rate, or maximal blood lactate concentration. vWf:Ag was significantly elevated (P <0.05)following PC [198.4 (18.3)% normal] versus AC [174.5 (15.6)% normal] and remained elevated 1-h post-exercise [179.4 (16.4)% normal for PC vs 158.6 (13.8)% normal for AC]. There were no differences between tests for tPA or PAI-1 activity, although tPA antigen was significantly elevated following PC versus AC (P <0.05). Following the cool-down, hematocrit was higher (P <0.05) for the PC test [48.90 (0.36)] compared with AC [47.43 (0.51)]. An AC reduces post-exercise vWf:Ag and tPA antigen without affecting tPA or PAI-1 activity.

Documentation of hazards and safety perceptions for mechanized logging operations in East Central Alabama.

The logging industry remains one of the most hazardous in the nation. Despite more stringent safety regulations and improvements in equipment safety features, the rate of logging fatalities has decreased at a much lower rate than the decrease in the rate of illnesses and injuries in the same occupation. The objective of this research was to identify and assess the hazards associated with logging operations in the Southeast region of the U.S. and propose interventions, taking into consideration the fact that, currently, most operations in the region are fully mechanized. Five logging crews in East Central Alabama participated in the study and were observed repeatedly during their normal operations. Researchers observed loggers engaging in multiple unsafe behaviors, but none of those led to an injury. The incidence of unsafe behaviors may be due in part to a lack of awareness of the hazards. Results indicate that Occupational Safety and Health Administration (OSHA) regulations appear to have little influence on logging safety. Loggers believe that most safety training recommendations are difficult to implement and negatively impact productivity. Thus, there seem to be fundamental drawbacks in the logging industry regarding effective delivery of safety training to loggers. The present study was a joint venture by the Industrial and Systems Engineering and Psychology departments of Auburn University, with support from the United States Forest Service (USFS).

Acute-onset nontraumatic paraplegia in childhood: fibrocartilaginous embolism or acute myelitis?

Fibrocartilaginous embolus causing acute spinal cord infarction is a rare cause of acute-onset paraplegia or quadriplegia. Few cases of survivors have been reported in the neurosurgical literature, with most reports involving postmortem or biopsy findings. There is little information on MRI findings in such patients. We present the youngest patient ever reported, and discuss the important differences between fibrocartilaginous embolus and acute myelitis of childhood. A 6-year-old girl with a history of back pain presented with sudden-onset nontraumatic paraplegia, with a clinical anterior spinal artery syndrome. Initial MRI scan revealed intervertebral disc disease at L1-2 and an incidental thoracic syrinx, but no cause for her acute-onset paraplegia was identified. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord expansion from T10 to the conus medullaris, with increased cord signal in the anterior aspect of the spinal cord. The intervertebral disc disease was unchanged. The imaging and clinical findings were caused by fibrocartilaginous embolus, which meant there was no need for spinal cord biopsy. The report describes the clinical and imaging criteria for diagnosis of fibrocartilaginous embolus, highlighting the case for avoiding an unnecessary biopsy. The clinical pattern in the paediatric group is discussed, with features differentiating it from acute myelitis of childhood.

Delayed presentation of transorbital intracranial pen.

A 13 year old Fijian boy sustained a stab wound to the left orbit 3 years ago. It was not appreciated by the treating physicians in Fiji that the plastic pen had crossed from the left orbit, through the nose, right orbit and right optic nerve, into the right middle cranial fossa and lodged in the right temporal lobe and that the pen remained in situ for the past 3 years. The boy presented to Australia with a discharge from the entry wound in his left lower eyelid. The retained foreign body was not detected on computed tomography imaging, but was detected on subsequent magnetic resonance image. A combined neurosurgery/plastic surgery craniofacial approach was undertaken with successful complete removal of the retained pen, and preservation of vision in his only seeing eye.

Accident reduction factors and causal inference in traffic safety studies: a review.

Accident reduction factors are used to predict the change in accident occurrence which a countermeasure can be expected to cause. Since ethical and legal obstacles preclude the use of randomized experiments when evaluating traffic safety improvements, empirical support for the causal effectiveness of accident countermeasures comes entirely from observational studies. Drawing on developments in causal inference initiated by Donald Rubin, it is argued here that the mechanism by which sites are selected for application of a countermeasure should be included as part of a study's data model, and that when important features of the selection mechanism are neglected, existing methods for estimating accident reduction factors become inconsistent. A promising, but neglected, way out of these difficulties lies in developing rational countermeasure selection methods which also support valid causal inference of countermeasure effects.

Microbial population changes during bioremediation of an experimental oil spill.

Three crude oil bioremediation techniques were applied in a randomized block field experiment simulating a coastal oil spill. Four treatments (no oil control, oil alone, oil plus nutrients, and oil plus nutrients plus an indigenous inoculum) were applied. In situ microbial community structures were monitored by phospholipid fatty acid (PLFA) analysis and 16S rDNA PCR-denaturing gradient gel electrophoresis (DGGE) to (i) identify the bacterial community members responsible for the decontamination of the site and (ii) define an end point for the removal of the hydrocarbon substrate. The results of PLFA analysis demonstrated a community shift in all plots from primarily eukaryotic biomass to gram-negative bacterial biomass with time. PLFA profiles from the oiled plots suggested increased gram-negative biomass and adaptation to metabolic stress compared to unoiled controls. DGGE analysis of untreated control plots revealed a simple, dynamic dominant population structure throughout the experiment. This banding pattern disappeared in all oiled plots, indicating that the structure and diversity of the dominant bacterial community changed substantially. No consistent differences were detected between nutrient-amended and indigenous inoculum-treated plots, but both differed from the oil-only plots. Prominent bands were excised for sequence analysis and indicated that oil treatment encouraged the growth of gram-negative microorganisms within the alpha-proteobacteria and Flexibacter-Cytophaga-Bacteroides phylum. alpha-Proteobacteria were never detected in unoiled controls. PLFA analysis indicated that by week 14 the microbial community structures of the oiled plots were becoming similar to those of the unoiled controls from the same time point, but DGGE analysis suggested that major differences in the bacterial communities remained.

Comparison of common cytotypesof Andropogon gerardii(Andropogoneae, Poaceae).

Many plant species contain populations with more than one polyploid cytotype, but little is known of the mechanisms maintaining several cytotypes in a population. Andropogon gerardii cytotypes were compared to evaluate different models of autopolyploid cytotype coexistence. The enneaploid (90 chromosome, 9x) cytotype was found to be larger and taller than the hexaploid (60 chromosome, 6x) cytotype. Seed production is significantly more efficient in hexaploids, but seed production per area was not significantly different. The two cytotypes are not exomorphologically separable in the field because of great plasticity in response to environmental variation and wide variation within each cytotype. These data suggest cytotypic variation is maintained by natural selection.

Clinical pharmacokinetics in the 21st century. Does the evidence support definitive outcomes?

Clinical pharmacokinetics emerged as a clinical discipline in the late 1960s and early 1970s. Clinical pharmacokinetic monitoring (CPM) helped many pharmacists to enter the clinical arena, but the focus was more on the pharmacists and tools. With the widespread acceptance of pharmaceutical care and patient-focused pharmacy, we now must take a sobering look at how clinical pharmacokinetics fits into the pharmaceutical care process. The existing literature is laden with articles that evaluate the effect of CPM on surrogate end-points. Many pharmacists have also had personal experiences that attest to the usefulness of CPM. Decreased mortality, decreased length of treatment, decreased length of hospital stay, decreased morbidity, and decreased adverse effects from drug therapy have been examined in an effort to measure and evaluate the impact of CPM on patient outcomes. While many of these studies demonstrated significant positive outcomes, several showed that CPM did not have a significant impact on specific patient outcomes. A few studies even found a negative impact on specific patient outcomes. Ultimately, there is good evidence in only a few specific patient groups to support the benefit of CPM. Despite the limitations of data supporting the routine use of CPM in managing drug therapy in diverse populations, many pharmacists continue to expend considerable time and effort in this activity. We need to define those patients who are most likely to benefit from CPM and incorporate this into our provision of pharmaceutical care, while minimising the time and money spent on CPM that provides no value. In redefining the patients who will benefit from CPM, we need to critically re-evaluate clinical studies on the relationship between drug concentration and response. Similarly, we need to pay special attention to recent studies evaluating the impact of CPM on outcomes in specific subpopulations. In the absence of specific studies demonstrating the value of CPM in particular patients, we propose that a more comprehensive decision-making process be undertaken that culminates in the quintessential question: 'Will the results of the drug assay make a significant difference in the clinical decision-making process and provide more information than sound clinical judgement alone?' We also need to consider opportunities to expand the use of CPM for new drugs and where new evidence suggests benefit. Even when there is strong evidence that CPM is useful in managing therapy in particular patient groups, clinicians need to remember that the therapeutic range is no more than a confidence interval and, therefore, we need to 'treat the patient and not the level'. We need to incorporate the patient-specific and outcome-oriented principles of pharmaceutical care into our CPM, even as we utilise CPM as an essential tool in pharmaceutical care.

Validation of the Hartford nomogram in trauma surgery patients.

OBJECTIVE: To validate the Hartford nomogram for once-daily aminoglycoside dosing in trauma surgery patients. METHODS: A chart review was performed in trauma surgery patients who were started on once-daily aminoglycoside therapy. A peak aminoglycoside concentration was drawn 30 minutes after the end of the first or second infusion, and a random concentration was drawn approximately 10 hours after the dose. The 10-hour random concentration was used to validate the Hartford nomogram by predicting the actual dosing interval (determined by extrapolating the peak and random concentrations to achieve a trough concentration <1 mg/L). The percentage of intervals accurately predicted by the nomogram was determined. RESULTS: Forty-nine patients (34 men and 15 women), age 43.0+/-15.9 y, total body weight 81.3+/-24.5 kg, ideal body weight 68.1+/-10.7 kg, dosing body weight (DBW) 72.0+/-14.4 kg, and estimated creatinine clearance [Cl(cr)] 89.5+/-20.6 mL/min/1.73 m2 were evaluated. Patients received 505+/-105 mg (7.0+/-0.4 mg/kg) of either gentamicin or tobramycin per dose. The concentration 30 minutes after the infusion was 22.4+/-5.9 mg/L, the concentration at the end of the dosing interval was 0.20+/-0.46 mg/L, the 10-hour random concentration was 2.6+/-1.8 mg/L, the elimination rate constant was 0.26+/-0.08 h(-1), the elimination half-life was 3.0+/-1.2 hours, and the volume of distribution was 19.9+/-7.9 L (0.28+/-0.09 L/kg of DBW). Ninety-eight percent (48/49) of the intervals were accurately predicted by the nomogram. CONCLUSIONS: In trauma surgery patients with Cl(cr) of more than 60 mL/min/1.73 m2, the Hartford nomogram using a single random aminoglycoside concentration accurately predicted the same once-daily aminoglycoside intervals as determined by two concentrations. Less aggressive therapeutic drug monitoring in this patient subpopulation can lead to significant cost savings.

Evaluation of aminoglycoside pharmacokinetics in postpartum patients using Bayesian forecasting.

Many postpartum women have suboptimal serum concentrations after standard doses of aminoglycosides. The purpose of this study was to characterize the pharmacokinetics of aminoglycosides in postpartum patients through the use of Bayesian forecasting and to test the ability of these subpopulation parameters to predict actual aminoglycoside serum concentrations. In phase I, 28 postpartum patients who received empiric gentamicin therapy were identified and Bayesian subpopulation parameters generated. In phase II, additional gentamicin concentrations (peaks and troughs) were evaluated to test bias and precision of Bayesian subpopulation versus traditional estimates in predicting actual aminoglycoside serum concentrations. In phase I, 56 gentamicin serum concentrations in 28 patients, (age, 26 +/- 7 years; actual body weight [ABW], 84.3 +/- 18.4 kg; ideal body weight [IBW], 54.6 +/- 5.1 kg; dosing weight [DW], 66.3 +/- 9.4 kg; creatinine clearance [Clcr], 140.4 +/- 34.0 ml/min / 1.73 m2), were evaluated to calculate subpopulation pharmacokinetic parameters of volume of distribution (Vd) 0.29 +/- 0.07 l/kg (DW); elimination rate constant (ke) 0.29 +/- 0.05 h-1 and half-life (t1/2) 2.5 +/- 0.5 hours. In phase II, 50 gentamicin serum concentrations in 25 patients (age, 23 +/- 4 years; ABW 79.4 +/- 17.5 kg; IBW 55.0 +/- 7.3 kg; DW 64.8 +/- 9.6 kg; Clcr 139.7 +/- 29.3 ml/min/1.73 m2) were evaluated to calculate subpopulation pharmacokinetic parameters of Vd 0.30 +/- 0.04 l/kg (DW); ke 0.27 +/- 0.06 h-1; and t1/2 2.9 +/- 0.8 hours. Predictive performance tests (95% confidence intervals) demonstrate that subpopulation postpartum Bayesian parameters show greater precision for peak concentrations and less bias for trough concentrations than do traditional population estimates (p < 0.05). Definition of the Bayesian subpopulation parameters will allow us to dose aminoglycosides optimally in postpartum patients who have fragmented data.

General versus subpopulation values in Bayesian prediction of aminoglycoside pharmacokinetics in hematology-oncology patients.

The predictive performance of Bayesian estimates incorporating pharmacokinetic values for hematology-oncology patients was compared with that of Bayesian estimates incorporating general population values. In study phase 1, medical records were reviewed for 50 adult patients with a hematologic or oncologic diagnosis who had received i.v. gentamicin or tobramycin. Aminoglycoside pharmacokinetic values were calculated for the patients by using a modified two-point Sawchuk-Zaske method, and the subpopulation mean for each variable was determined. In phase 2, data for 10 other hematology-oncology patients receiving aminoglycosides were entered into the Abbottbase Bayesian pharmacokinetics program. Aminoglycoside pharmacokinetic values and serum concentrations for each of these 10 patients were estimated, first using the program's general population values and then repeating the analysis using the subpopulation means for volume of distribution and renal clearance slope obtained in phase 1. The serum aminoglycoside concentrations predicted by each Bayesian method were compared with the actual peaks and troughs. Both the peak and trough predictions of the Abbottbase program using the subpopulation values for volume of distribution and renal clearance slope were significantly less biased than those predicted by the Abbottbase program incorporating the general population values. The methods did not differ significantly in precision. Use of subpopulation pharmacokinetic values in Bayesian predictions of serum aminoglycoside concentrations in hematology-oncology patients reduced bias significantly but had no significant effect on precision.