A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Effects of space allowance and marketing strategy on growth performance of pigs raised to 165 kg.

A total of 976 pigs (PIC 327 × Camborough; PIC, Hendersonville, TN; initially 22.0 ± 1.53 kg body weight [BW]) were used in a 160-d growth study to evaluate the effects of increasing space allowance and varying marketing strategies on growth performance of pigs raised to market weights of ~165 kg. Pens of pigs were blocked by location within the barn and allotted to one of six treatments. Pen served as the experimental unit, and there were eight replicate pens per treatment. The first four treatments consisted of increased initial stocking density and did not utilize topping strategies: (1) 14 pigs/pen (1.17 m2/pig), (2) 17 pigs/pen (0.97 m2/pig), (3) 20 pigs/pen (0.82 m2/pig), and (4) 23 pigs/pen (0.71 m2/pig). The fifth treatment began with 25 pigs/pen (0.66 m2/pig) and had four marketing events with the heaviest 3 pigs/pen removed on day 93, and additional pigs removed to a common inventory of 20 pigs/pen on day 122 and 17 pigs/pen on day 147 with final marketing on day 160. The final treatment began the experiment with 23 pigs/pen (0.71 m2/pig) with three marketing events to achieve a common inventory of 20 pigs/pen on day 108 and 17 pigs/pen on day 147. Pens of pigs were weighed and feed disappearance measured on days 0, 55, 93, 108, 122, 135, 147, and 160. As space allowance decreased from 1.17 to 0.71 m2/pig via increased initial pen inventory (treatments 1 to 4), overall average daily gain (ADG) and average daily feed intake (ADFI) decreased (linear, P < 0.001), while gain:feed ratio (G:F) did not differ (P > 0.05). The treatments with multiple marketing events were compared with each other and with the treatment that began with 0.71 m2/pig and only marketed once at the end of the study. Overall ADG and ADFI were not different (P > 0.05) among these three treatments. Marketing pigs three or four times improved (P < 0.05) G:F compared with the treatment that began the study with 0.71 m2/pig and marketed only once. Reducing floor space allowance for heavy weight pigs decreased intake, which resulted in lower growth rate and final BW, with these reductions occurring before the critical k-value was reached. Total weight gain per pen was maximized with the lowest space allowance and the multiple marketing treatments. Thus, strategic use of pig removals prior to final marketing may allow producers to maximize both number of pigs and total weight marketed through a barn when feeding to heavy weights.

Final internal cooking temperature of pork chops influenced consumer eating experience more than visual color and marbling or ultimate pH.

The objective was to determine the effect of "quality grade" (combination of visual color and marbling) or ultimate pH on consumer eating experience of pork chops cooked to different final internal temperatures. The hypothesis was that consumers would rate a greater percentage of pork chops as acceptable when graded "choice," had a greater ultimate pH, or when cooked to 63 °C compared with chops graded "standard," had a lesser ultimate pH, or when cooked to 71 or 82 °C. Consumers (264 total) were served chops in 1 of 2 experiments. Chops in Exp. 1 were classified as "choice" when NPPC visual color score ≥3 and visual marbling score was ≥2 or "standard" when NPPC scores did not meet the qualifications for "choice" and were cooked to either 63 or 71 °C. Chops in Exp. 2 were categorized as high pH (5.88 to 6.23) or low pH (5.36 to 5.56) and cooked to 63, 71, or 82 °C. Chops were cooked with a sous-vide device (ANOVA Precision Cooker, Anova Applied Electronics, San Francisco, CA) in a water bath. Consumers used a 9-point Likert-type score system where scores 1 through 3 were considered not tender, not juicy, not flavorful, or unacceptable. Scores 4 through 6 were consider neutral for tenderness, juiciness, flavor, and overall acceptability. Scores 7 through 9 were considered tender, juicy, flavorful, and acceptable. Data were organized as a percentage of responses and analyzed using the GLIMMIX procedure of SAS for both experiments with models including treatment (quality grade, ultimate pH, and final internal temperature) and all interactions. Quality grade did not affect (P ≥ 0.30) consumer ratings for any sensory trait. More (P < 0.01) consumers rated chops with a high pH (36.07%) as juicy compared with chops with a low pH (24.29%), but pH category did not alter (P ≥ 0.13) perceptions for tenderness, flavor, or overall acceptability. In both studies, a greater (P < 0.001) percentage of consumers rated chops cooked to 63 °C as acceptable compared with chops cooked to 71 °C. Therefore, internal cooking temperature has a greater impact on consumer eating experience than "quality grade" or ultimate pH.

The effects of ultimate pH and color on sensory traits of pork loin chops cooked to a medium-rare degree of doneness.

The objective was to determine the effects of pH and color on sensory characteristics of boneless pork loin chops cooked to an internal endpoint temperature of 63 °C. Center cut loins (296 total) from barrows and gilts, 5 different sire lines, and a range in pH of 5.36 through 6.23 were used. Previously, ultimate pH was correlated with sensory characteristics of chops cooked to a medium (71 °C) degree of doneness. Additionally, increasing ultimate pH improved sensory tenderness and juiciness of loin chops cooked to a medium degree of doneness. However, in 2011, the United States Department of Agriculture Food Safety and Inspection Service reduced the recommended final internal cooking temperature of pork chops from 71 to 63 °C (followed by a 3-min rest). The effects of ultimate pH on sensory traits of pork chops cooked to a medium-rare (63 °C) degree of doneness are not known. Therefore, loins were categorized using historical categories based on ultimate pH: >5.95, n = 22; 5.80 to 5.95, n = 75; 5.65 to 5.80, n = 102; 5.50 to 5.65, n = 91; <5.50, n= 6. On 1-d postmortem, loins were evaluated for CIE instrumental L*, a*, b*, visual color, marbling, and subjective firmness. Then, loins were aged in vacuum packages at 4 °C until 16-d postmortem. After aging, loins were cut into 2.54-cm thick chops, vacuum-packaged, and frozen until sensory or instrumental tenderness analysis. One chop was also used to determine extractable lipid. Chops were weighed, cooked to 63 °C, cooled to approximately 23 °C, weighed again to determine cook loss, and then evaluated for Warner-Bratzler shear force. Another chop was cooked to 63 °C internal temperature and served warm to trained panelists to determine sensory traits. Coefficients of determination (R2) were calculated to determine the predictability of ultimate pH and instrumental color on sensory tenderness, juiciness, and flavor. A 1-way ANOVA and means separation test were used to determine specific differences among pH categories. Ultimate pH explained less than 5% of the variation in tenderness and less than 1% of the variation in juiciness or flavor. Furthermore, sensory tenderness did not differ (P > 0.05) among pH categories, except for chops with an ultimate pH > 5.95. Chops with a pH > 5.95 were at least 9.1% more tender (P < 0.05) than chops with a pH < 5.95. Visual and instrumental color were not predictive (R2 ≤ 0.03) of any sensory traits. Overall, pH does not influence sensory traits of pork chops cooked to medium-rare degree of doneness unless pH is at least 5.95.

Pharmacokinetics of Lidocaine and Its Metabolites Following Vaginal Administration of Lidocaine Gel to Healthy Female Subjects.

Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single-dose and multiple-dose studies in healthy young adult women. Lidocaine doses of 2.5%, 5%, and 10% (w/w) were administered, and parent drug and metabolites monoethylglycinexylidide and glycinexylidide were measured in plasma. Lidocaine was absorbed through vaginal tissue and into the systemic circulation in a dose-proportional manner, and there was little systemic accumulation. Plasma concentrations were 10- to 20-fold lower than concentrations obtained after administration of intravenous lidocaine used to treat arrhythmic activity, thus demonstrating a wide safety margin for a vaginal lidocaine product.