Carryover effects of temperature and pCO2 across multiple Olympia oyster populations.

Predicting how populations will respond to ocean change across generations is critical to effective conservation of marine species. One emerging factor is the influence of parental exposures on offspring phenotype, known as intergenerational carryover effects. Parental exposure may deliver beneficial or detrimental characteristics to offspring that can influence larval recruitment patterns, thus shaping how populations and community structure respond to ocean change. Impacts of adult exposure to elevated winter temperature and pCO2 on reproduction and offspring viability were examined in the Olympia oyster (Ostrea lurida) using three populations of adult, hatchery-reared O. lurida, plus an additional cohort spawned from one of the populations. Oysters were sequentially exposed to elevated temperature (+4°C, at 10°C), followed by elevated pCO2 (+2,204 µatm, at 3,045 µatm) during winter months. Male gametes were more developed after elevated temperature exposure and less developed after high pCO2 exposure, but there was no impact on female gametes or sex ratios. Oysters previously exposed to elevated winter temperature released larvae earlier, regardless of pCO2 exposure. Those exposed to elevated winter temperature as a sole treatment released more larvae on a daily basis but, when also exposed to high pCO2 , there was no effect. These combined results indicate that elevated winter temperature accelerates O. lurida spermatogenesis, resulting in earlier larval release and increased production, with elevated pCO2 exposure negating effects of elevated temperature. Altered recruitment patterns may therefore follow warmer winters due to precocious spawning, but these effects may be masked by coincidental high pCO2 . Offspring were reared in common conditions for 1 yr, then deployed for 3 months in four estuarine bays with distinct environmental conditions. Offspring of parents exposed to elevated pCO2 had higher survival rates in two of the four bays. This carryover effect demonstrates that parental conditions can have substantial ecologically relevant impacts that should be considered when predicting impacts of environmental change. Furthermore, Olympia oysters may be more resilient in certain environments when progenitors are pre-conditioned in stressful conditions. Combined with other recent studies, our work suggests that the Olympia may be more equipped than other oysters for the challenge of a changing ocean.

Medical resource utilization for administration of trastuzumab in a New Zealand oncology outpatient setting: a time and motion study.

BACKGROUND: In New Zealand, trastuzumab is standard therapy for human epidermal growth factor receptor-2 (HER2)-positive early and metastatic breast cancer. Given the requirement for ongoing adjuvant or maintenance treatment and intravenous (IV) delivery, such a regimen consumes considerable health care resources. The development of a subcutaneous (SC) trastuzumab formulation with a short administration time offers the potential to reduce hospital expenditure. The aim of this study was to determine medical resource utilization associated with administration of trastuzumab SC injection via handheld syringe vs trastuzumab IV infusion in patients with HER2-positive breast cancer in New Zealand. METHODS: This noninterventional, descriptive study was conducted at the outpatient oncology centers at Auckland City and Tauranga Hospitals. Trained observers recorded times associated with health care professional (HCP) tasks and consumables use associated with preparation and administration of trastuzumab IV or SC in women with early or metastatic breast cancer. The cost for each formulation was calculated as the mean cost of HCP time (based on Pharmaceutical Management Agency hourly rates) plus the mean cost of consumables used. RESULTS: Use of trastuzumab SC vs IV reduced mean chair time by 36.95 minutes and total nurse time by 6.12 minutes; there was a 20.45-minute reduction in pharmacist time when the SC formulation was used. After adding consumable costs, the overall estimated saving with trastuzumab SC vs IV was $76.94 (New Zealand dollars) per patient per cycle. CONCLUSIONS: Compared with trastuzumab IV infusion, administration of trastuzumab via SC injection reduced time spent in the clinic and decreased HCP resources and consumables needed to administer treatment. These reductions could contribute to a decrease in health care costs and an improvement in the efficiency of HER2-positive breast cancer treatment delivery.

Antimicrobial Effects of Novel Triple Antibiotic Paste-Mimic Scaffolds on Actinomyces naeslundii Biofilm.

INTRODUCTION: Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)-mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. METHODS: Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm(3), n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. RESULTS: Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly (P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant (P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS. CONCLUSIONS: Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics.

Clinical trial participation improves outcome: a matched historical cohort study.

BACKGROUND: Well-conducted, investigator-led randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of new treatments and are a key component of evidence-based medicine. It is unclear whether participating in an RCT is beneficial to the individual before the results of RCTs are known. PURPOSE: In a matched historical cohort study, we examined whether participation in RCTs was associated with improved health outcomes. METHODS: Participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), or Telmisartan Randomized Assessment Study in ACE-intolerant Subjects with Cardiovascular Disease (TRANSCEND) studies and non-participant controls were selected from patients attending outpatient clinics at Middlemore Hospital between 2001 and 2003. RESULTS: A total of 251 RCT participants and 502 randomly selected patients not enrolled in a trial but who met study entry criteria were matched for age, gender, and ethnicity. There was a significant difference in all-cause mortality for trial participants versus non-participants over the study period (unadjusted relative risk reduction (RRR) = 63%; 95% confidence interval (CI) = 28%-81%) and a significant reduction in cardiovascular mortality (unadjusted RRR = 81%; 95% CI = 17%-95%) favouring RCT participants. Allowing for co-morbidity, the adjusted RRR of all-cause mortality associated with trial participation was 55% (95% CI = 10%-77%). Active treatment in an RCT was found to be less explanatory than trial participation. The adjusted RRR for cardiovascular mortality associated with active treatment in a trial was 86% (95% CI = -2% to 98%), with trial participation found to be less explanatory than active treatment. LIMITATIONS: The main limitations of this trial relate to its design as a retrospective study with a historical cohort comparison group. Limitations include lack of complete data for some patients, bias in selection of the comparison group, and the effects of confounding variables. However, the study design and analysis were planned so as to minimize these as much as possible. CONCLUSION: This study revealed significantly lower all-cause mortality among participants in industry-sponsored RCTs compared with non-participants who received routine hospital outpatient care. This effect was independent of study drug.

Body-shape perceptions in older adults and motivations for exercise.

This study examined the relationships among age, sex, exercise and body-image dissatisfaction in older adults and evaluated the role of body-shape dissatisfaction as a motivation to exercise. A pencil-and-paper questionnaire was administered to 175 older adults (101 women and 74 men) ranging in age from 50 to 98 years (M=72 yr., SD=9) to obtain general information, information regarding exercise participation, motivations for exercise and body-shape perceptions. A body-shape dissatisfaction score was calculated using the difference between the participant's choice for current and ideal body shape from a nine-figure body-silhouette scale. Present study findings suggested that both older adult men and women expressed a desire for a thinner body shape independent of age and current participation in exercise. In addition, the results indicated that body-shape dissatisfaction did not motivate this sample to engage in regular exercise; physical health and physical fitness emerged as the most important motivations to exercise.

Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity.

OBJECTIVE: To test whether a reduction in air temperature within the clinical range [37 degrees C to 30, 100% relative humidity (RH)] altered mucus transport velocity (MTV) and ciliary beat frequency (CBF) in an in vitro ovine tracheal model. DESIGN: Controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Farm-reared sheep. INTERVENTIONS: Tracheae were mounted flat in an organ bath. Krebs Henseleit bathed the serosal surface and air at 100% (RH) was passed over the mucosal surface at 4 l/min. Cilial beat frequency (CBF) was measured photo-electrically and mucus transport velocity (MTV) by timing movement. After 2 h at 37 degrees C (100% RH) the tissue was either maintained with those settings (controls), or the air temperature reduced to 34 degrees C or 30 degrees C. Tissue was taken for histology before and after each experiment. MEASUREMENTS AND RESULTS: CBF was 19.8+/-2.7 beats/s and MTV 5.7+/-2.6 mm/min in tissue exposed to air at 37 degrees C. Cilial activity continued for up to 6 h in the controls but mucus transport was more fragile. Reduction of the air temperature to either 34 degrees C or 30 degrees C led to a decrease in both CBF and MTV and, frequently, total mucociliary failure. There was a reduction in epithelial mucous cell numbers in all preparations. Tissues exposed to low temperature had additional abnormal histology. CONCLUSIONS: Delivery of inspired gas at 30 degrees C, or even 34 degrees C, with 100% RH may not be sufficient to prevent epithelial damage occurring during 6 h exposure.

Identification and characterisation of proteinase inhibitors and their genes from seeds of apple (Malus domestica).

Trypsin and papain proteinase inhibitors have been identified and purified from aqueous extracts of apple seeds (Malus domestica). Superdex G75 gel filtration chromatography identified a higher molecular weight (HMW) papain inhibitory fraction (22-26 kDa) and a lower molecular weight papain and trypsin inhibitory fraction (6-12 kDa). The lower molecular weight fraction was separated into a trypsin inhibitor (designated Trp1) and early (designated Pap1) and late (designated Pap2) eluting papain inhibitors after anion exchange (Hitrap SP) chromatography. For Pap2, two inhibitory peaks (designated Pap2-1 and Pap2-2) were identified after further anion exchange (Resource S) chromatography. Each of these lower molecular weight inhibitors was purified by reverse phase HPLC to homogeneity as determined by SDS-PAGE and by mass spectrometry. The HMW papain inhibitory fraction was purified further by anion-exchange (Hitrap Q followed by Resource Q) column chromatography where a minor inhibitor (HMWPap1) and major inhibitor (HMWPap2) fraction were identified. The relative abundance in seeds of apple and the spectrum of proteinase inhibition has been determined for all of these inhibitors. Reverse-phase HPLC separated HMWPap2 into a minor (HMWPap2-1) and a major (HMWPap2-2) inhibitory fraction, and SDS-PAGE and mass spectrometry confirmed that HMWPap2-2 was purified to homogeneity. Amino acid composition data were obtained from Trp1, Pap1, Pap2-2, and HMWPap2-2, and N-terminal sequence data from Trp1, Pap2-1, Pap2-2, and HMWPap2-2, with two of these sequences (Pap2-2 and HMWPap2-2) perfectly matching predicted protein sequences based on EST sequences from an apple database. The relationship of these inhibitors with those of other species is discussed.

Extensions of the lost letter technique to divisive issues of creationism, darwinism, sex education, and gay and lesbian affiliations.

Two field studies using 1,004 "lost letters" were designed to test the hypotheses that returned responses would be greater in small towns than from a city, that addressees' affiliation with a group either (1) opposed to physical education in schools, (2) supporting gay and lesbian teachers, or (3) advocating Creationism or Darwinism would reduce the return rate. Of 504 letters "lost" in Study A, 163 (32.3%) were returned in the mail from residents of southeast Louisiana and indicated across 3 addressees and 2 sizes of community, addressees' affiLiations were not associated with returned responses. Community size and addressees' affiliations were associated with significantly different rates of return in the city. Return rates from sites within a city were lower when letters were addressed to an organization which opposed (teaching) health education in the schools than to one supporting daily health education. Of 500 letters "lost" in Study B, 95 (19.0%) were returned from residents of northwest Florida and indicated across 5 addressees and 2 sizes of community, addressees' affiliations were significantly associated with returned responses overall (5 addressees) and in small towns (control, Creationism, Darwinism addressees), but not with community size. Community size and addressees' affiliations were associated with significantly different rates of return in small towns, with returns greater than or equal to those in the city (except for the addressee advocating teaching Darwinism in public schools). The present findings appear to show that applications of the lost letter technique to other divisive social issues are useful in assessing public opinion.

Energy balance in the intubated human airway is an indicator of optimal gas conditioning.

OBJECTIVE: The optimal level of inspired heat and humidity for patients receiving long-term mechanical ventilation is still the subject of debate. Many laboratory studies examining surrogate markers for optimal humidity suggest that inspired gas should be at body temperature and fully saturated. The aim of this study was to determine the inspired gas condition that was thermodynamically neutral to the airway of intubated patients, and also examine the contribution of the endotracheal tube to airway heat and water balance. DESIGN: Prospective, block-randomized, observational study. SETTING: General adult intensive care unit of a metropolitan teaching hospital. PATIENTS: Ten adult patients requiring intermittent positive pressure ventilation for nonpulmonary reasons. INTERVENTIONS: Each patient was given four different gas conditions--30 degrees C, 30 mg/L; 34 degrees C, 38 mg/L; 37 degrees C, 44 mg/L; and 40 degrees C, 50 mg/L--to breathe in random order. MEASUREMENTS AND MAIN RESULTS: Inspired and expired gas temperature and humidity, and the temperature gradient down the endotracheal tube, were measured and the inspired gas condition that gave thermodynamic neutrality was determined. This was found to be gas at body temperature, saturated. Airway workload and airway water loss increased linearly as the inspired gas departed from this condition, at approximately 1.4 kJ/hr/ degrees C and 0.5 mL/hr/ degrees C, respectively. The endotracheal tube contributed very little to heat and water exchange. CONCLUSIONS: Inspired gas at body temperature and saturated is thermodynamically neutral to the intubated airway, and thus may be considered the optimal condition for ventilation lasting more than a few hours.