Population-based germline breast cancer gene association studies and meta-analysis to inform wider mainstream testing.

BACKGROUND: Germline genetic testing, previously restricted to familial and young-onset breast cancer, is now offered increasingly broadly to 'population-type' breast cancer patients in mainstream oncology clinics, with wide variation in the genes included. METHODS: Weighted meta-analysis was performed for three population-based case-control studies (BRIDGES, CARRIERS and UK Biobank) comprising in total 101,397 women with breast cancer and 312,944 women without breast cancer, to quantify for 37 putative breast cancer susceptibility genes (BCSGs) the frequency of pathogenic variants (PVs) in unselected, 'population-type' breast cancer cases and their association with breast cancer and its subtypes. RESULTS: Meta-analysed odds ratios (ORs) and frequencies of PVs in population-type breast cancer cases were generated for BRCA1 (OR= 8.73 (95% CI 7.47-10.20), 1 in 101), BRCA2 (OR=5.68 (5.13-6.30), 1 in 68) and PALB2 (OR= 4.30 (95% CI 3.68-5.03), 1 in 187). For both CHEK2 (OR=2.40 (95% CI 2.21-2.62), 1 in 73) and ATM (OR=2.16 (95%CI 1.93-2.41), 1 in 132) subgroup analysis showed stronger association with ER-positive disease. Magnitude of association and frequency of PVs were low for RAD51C (OR=1.53 (95%CI 1.15-2.04), 1 in 913), RAD51D (OR=1.76, (95%CI 1.15-2.41, 1 in 1079) and BARD1 (OR=2.34 (1.85-2.97), 1 in 672); frequencies and associations were moderately higher restricting to triple-negative breast cancers The PV-frequency in 'population-type' breast cancer cases was very low for 'syndromic' BCSGs TP53 (1 in 1844), STK11 (1 in 11,525), CDH1 (1 in 2668), PTEN (1 in 3755) and NF1 (1 in 1470), with metrics of association also modest ranging from OR=3.62 (95%CI 1.98-6.61) for TP53 down to OR=1.60 (95%CI 0.48-5.30) for STK11. CONCLUSIONS: These metrics reflecting 'population-type' breast cancer will be informative to defining the appropriate gene set as we continue to expand to germline testing out to more unselected population-type breast cancer cases.

Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Effect of spineless cactus [Nopalea cochenillifera (L.) Salm Dyck] on nutrient intake, ingestive behaviour, and performance of lambs.

The objective of this study was to evaluate the effect of increasing levels of spineless cactus (SC) [Nopalea cochenillifera (L.) Salm Dyck] on nutrient intake, ingestive behaviour, and performance of lambs in a feedlot. Thirty-two male (non-castrated) Santa Inês lambs with a mean initial body weight (BW) of 20.4 ± 2.60 kg were distributed across four levels of spineless cactus: zero, 24, 52, and 75% of total diet dry matter (DM). Over 56 days, the animals had their intake and performance monitored. The inclusion of SC influenced (p<0.05) in a quadratic way the dry matter intake and total digestible nutrients, but linearly decreased (p<0.05) the neutral detergent fiber intake. Drinking water intake decreased linearly (p<0.05) with the inclusion of SC in the diet. The inclusion of SC influenced (p<0.05) in a quadratic way the digestibility of organic matter in the diet. The increase in the level of SC in the diet increased linearly (p<0.05) the feeding and rumination efficiencies of the lambs. The maximum daily gain of 0.237 kg/day was achieved with 44% SC in the diet. It is recommended to include up to 40% of spineless cactus in the diet of lambs.

Productive performance, breast growth and digestive system development in European quail subjected to post-hatch fasting for different periods.

This study assessed the effect of different periods of post-hatch fasting on animal performance and breast and digestive system growth in European quail. Quail chicks were distributed in a completely randomized design, with four fasting periods (0, 24, 36, and 48 hs) and four replications of 40 birds per treatment. In 1 to 14-day-old chicks, weight gain decreased with increasing fasting time. Compensatory gain was observed from 15 days of age onward. Fasted quail had a lower length and relative weight of the digestive system than fed animals for up to 14 days. Histologically, the duodenal villus height was significantly lower in 3-day-old quail fasted for 36 hs than in those fasted for 48 hs, but this effect was not observed at 7 days. Scanning electron microscopy showed no differences in the small intestinal mucosa between fasted and fed birds at 3 days of age. Post-hatch fasting reduced the relative weight of the breast in quail aged 1 to 14 days but did not affect type IIa and IIb fiber diameter at 35 days. On the basis of these results, it is recommended that European quail raised for meat should not be fasted for more than 48 hs post-hatch.

Citywide Integrated Aedes aegypti Mosquito Surveillance as Early Warning System for Arbovirus Transmission, Brazil.

Arbovirus epidemiology lacks efficient and timely surveillance systems with accurate outbreak alert signals. We devised a citywide integrated surveillance system combining entomologic, epidemiologic, and entomo-virologic data gathered during 2017-2020 in Foz do Iguaçu, Brazil. We installed 3,476 adult mosquito traps across the city and inspected traps every 2 months. We compared 5 entomologic indices: traditional house and Breteau indices for larval surveys and trap positivity, adult density, and mosquitoes per inhabitant indices for adult trapping. We screened for dengue, Zika, and chikungunya viruses in live adult Aedes aegypti mosquitoes collected from traps. Indices based on adult mosquito sampling had higher outbreak predictive values than larval indices, and we were able to build choropleth maps of infestation levels <36 h after each round of trap inspection. Locating naturally infected vectors provides a timely support tool for local public health managers to prioritize areas for intervention response to prevent virus outbreaks.

Comprehensive assessment of germline pathogenic variant detection in tumor-only sequencing.

BACKGROUND: Tumor-only sequencing, implemented for the identification of somatic variants, is oftentimes used for the detection of actionable germline variants. We sought to determine whether tumor-only sequencing assays are suitable for detection of actionable germline variants, given their importance for the delivery of targeted therapies and risk-reducing measures. PATIENTS AND METHODS: The detection of germline variants affecting moderate- and high-penetrance cancer susceptibility genes (CSGs) by tumor-only sequencing was compared to clinical germline testing in 21 333 cancer patients who underwent tumor and germline testing using the Food and Drug Administration (FDA)-authorized Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay. Seven homologous recombination deficiency (HRD), two DNA damage response (DDR) and four mismatch repair (MMR) genes, as well as NF1, RB1 and TP53 were included in the analysis. FDA-authorized and New York State Department of Health-approved sequencing methods for germline, tumor/normal and tumor-only sequencing assays and analytical pipelines were employed. RESULTS: In patients who underwent tumor and germline sequencing, as compared to clinical genetic testing, tumor-only sequencing failed to detect 10.5% of clinically actionable pathogenic germline variants in CSGs, including 18.8%, 12.8% and 7.3% of germline variants in MMR, DDR and HRD genes, respectively. The sensitivity for detection of pathogenic germline variants by tumor-only sequencing was 89.5%. Whilst the vast majority of pathogenic germline exonic single-nucleotide variants (SNVs) and small indels were detected by tumor-only sequencing, large percentages of germline copy number variants, intronic variants and repetitive element insertions were not detected. CONCLUSIONS: Tumor-only sequencing is adequate for the detection of clinically actionable germline variants, particularly for SNVs and small indels; however, a small subset of alterations affecting HRD, DDR and MMR genes may not be detected optimally. Therefore, for high-risk patients with negative tumor-only sequencing results, clinical genetic testing could be considered given the impact of these variants on therapy and genetic counseling.

Analysis of mutation status and homologous recombination deficiency in tumors of patients with germline BRCA1 or BRCA2 mutations and metastatic breast cancer: OlympiAD.

BACKGROUND: Presence of a germline BRCA1 and/or BRCA2 mutation (gBRCAm) may sensitize tumors to poly(ADP-ribose) polymerase (PARP) inhibition via inactivation of the second allele, resulting in gene-specific loss of heterozygosity (gsLOH) and homologous recombination deficiency (HRD). Here we explore whether tissue sample testing provides an additional route to germline testing to inform treatment selection for PARP inhibition. PATIENTS AND METHODS: In this prespecified exploratory analysis, BRCA1 and/or BRCA2 mutations in blood samples (gBRCAm) and tumor tissue (tBRCAm) were analyzed from patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer and known gBRCAm, enrolled in the phase III OlympiAD trial. The frequency and nature of tBRCAm, HRD score status [HRD-positive (score ≥42) versus HRD-negative (score <42) using the Myriad myChoice® CDx test] and rates of gsLOH were determined, and their impact on clinical efficacy (objective response rate and progression-free survival) was explored. RESULTS: Tissue samples from 161/302 patients yielded tBRCAm, HRD and gsLOH data for 143 (47%), 129 (43%) and 125 (41%) patients, respectively. Concordance between gBRCAm and tBRCAm was 99%. gsLOH was observed in 118/125 (94%) patients [BRCA1m, 73/76 (96%); BRCA2m, 45/49 (92%)]. A second mutation event was recorded for two of the three BRCA1m patients without gsLOH. The incidence of HRD-negative was 16% (21/129) and was more common for BRCA2m (versus BRCA1m) and/or for hormone receptor-positive (versus triple-negative) disease. Olaparib antitumor activity was observed irrespective of HRD score. CONCLUSIONS: gBRCAm identified in patients with HER2-negative metastatic breast cancer by germline testing in blood was also identified by tumor tissue testing. gsLOH was common, indicating a high rate of biallelic inactivation in metastatic breast cancer. Olaparib activity was seen regardless of gsLOH status or HRD score. Thus, additional tumor testing to inform PARP inhibitor treatment selection may not be supported for these patients.

Sanitizer efficacy in reducing microbial load on commercially grown hydroponic lettuce.

BACKGROUND: Most hydroponic lettuce growers harvest and package their marketable-size lettuces with an intact root ball. With a high microbial load on the peat moss substrate, there is a risk of microbial transfer onto the edible portion during packaging and throughout the product's shelf life. Since the produce is believed to have no contact with the substrate, no sanitizer wash is performed before packaging and storage. RESULTS: Aerobic plate count (APC) results suggested that reduction in count was influenced by both sanitizer application and storage time. Peroxyacetic acid significantly reduced APC count on leaves, roots, and substrate, with a 1.8 log CFU g-1 initial reduction on the leaf. Fungi and APC levels increased with storage time, with the greatest APC increase in the roots. Leaves had the lowest coliform bacteria (CB), with chlorine slightly reducing CB count. Unlike APC, CB levels decreased during storage on the substrate and root samples. No Listeria positive was confirmed by agglutination test. Further evaluation of different commercial substrates reveals that Com4, a drier-compacted plug, had the least ability to support growth/survival of all microbial populations enumerated relative to the spongy, wet black plugs. CONCLUSION: The ability of peat moss substrates to host microorganisms is influenced by the physical properties of the product. Sanitizer wash efficacy is dependent on the initial microbial load and the length of storage. Chlorine and peroxyacetic acid are effective in reducing microbial populations on the leaves of hydroponically grown lettuce without affecting visual quality during shelf life. © 2020 Society of Chemical Industry.

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer.

BACKGROUND: In the OlympiAD study, olaparib was shown to improve progression-free survival compared with chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA1 and/or BRCA2 mutation (BRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). We now report the planned final overall survival (OS) results, and describe the most common adverse events (AEs) to better understand olaparib tolerability in this population. PATIENTS AND METHODS: OlympiAD, a Phase III, randomized, controlled, open-label study (NCT02000622), enrolled patients with a germline BRCAm and HER2-negative mBC who had received ≤2 lines of chemotherapy for mBC. Patients were randomized to olaparib tablets (300 mg bid) or predeclared TPC (capecitabine, vinorelbine, or eribulin). OS and safety were secondary end points. RESULTS: A total of 205 patients were randomized to olaparib and 97 to TPC. At 64% data maturity, median OS was 19.3 months with olaparib versus 17.1 months with TPC (HR 0.90, 95% CI 0.66-1.23; P = 0.513); median follow-up was 25.3 and 26.3 months, respectively. HR for OS with olaparib versus TPC in prespecified subgroups were: prior chemotherapy for mBC [no (first-line setting): 0.51, 95% CI 0.29-0.90; yes (second/third-line): 1.13, 0.79-1.64]; receptor status (triple negative: 0.93, 0.62-1.43; hormone receptor positive: 0.86, 0.55-1.36); prior platinum (yes: 0.83, 0.49-1.45; no: 0.91, 0.64-1.33). Adverse events during olaparib treatment were generally low grade and manageable by supportive treatment or dose modification. There was a low rate of treatment discontinuation (4.9%), and the risk of developing anemia did not increase with extended olaparib exposure. CONCLUSIONS: While there was no statistically significant improvement in OS with olaparib compared to TPC, there was the possibility of meaningful OS benefit among patients who had not received chemotherapy for metastatic disease. Olaparib was generally well-tolerated, with no evidence of cumulative toxicity during extended exposure. Please see the article online for additional video content.

Modeling selective-area growth of InAsSb nanowires.

An analytical growth model is presented to explain the influence of antimony fractional flux on the morphology evolution of catalyst-free InAs1-x Sb x semiconductor nanowires grown by the selective-area vapor-solid mechanism on a Si (111) substrate by molecular beam epitaxy. Increasing Sb fractional flux promoted radial growth and suppressed axial growth, resulting in 'nano-disks'. This behavior is explained by a model of indium adatom diffusion along nanowire facets.

Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study.

Background: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer. Patients and methods: Eligible patients ≥18 years with locally recurrent or metastatic breast cancer and a deleterious BRCA1/2 germline mutation were randomized 1 : 1 : 1 to VCP, VT, or placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and overall response rate (ORR). Results: Of 290 randomized patients, 284 were BRCA+, confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3 months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227], interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156), and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4 months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P < 0.001). Safety profile was comparable between carboplatin/paclitaxel arms. Adverse events (all grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with VT versus PCP. Conclusion: Numerical but not statistically significant increases in both PFS and OS were observed in patients with BRCA1/2-mutated recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional continuation single-agent therapy with veliparib/placebo if chemotherapy is discontinued without progression, in this patient population. Clinical trial information: NCT01506609.

Where does the Albumin go? Human Albumin Solution usage following the implementation of a demand management programme.

OBJECTIVE: To outline the Guy's and St Thomas' NHS Foundation Trust (GSTFT) and Evelina London Children's Hospital (ELCH) demand management plan for human albumin solution (HAS) and usage. BACKGROUND: There is no UK-wide guidance governing the use of HAS. A severe shortage in 2015 prompted a Trust demand management programme. Indications were categorised according to locally agreed colour code and ASFA categories. METHODS: Following the implementation of the demand management programme, a 6-month audit of HAS usage was completed. RESULTS: A total of 1303.1 L of HAS was used in 1139 infusions; 737 infusions were 20% HAS, accounting for 175.7 L (13.5%) in 181 patients. Indications for 20% HAS were red in 53.9% (94.7 L), blue in 26.5% (46.5 L) and grey in 19.6% (34.5 L). The remaining 1127.4 L (86.5%) infused were of 4.5 and 5 % HAS. A total of 1102.3 L (97.8%) was used for plasma exchange, 941.4 L (85.4%) ASFA category I, 93.7 L (8.5%) category II, 25.5 L (2.3%) category IV and 41.7 L (3.8%) for indications not specified according to ASFA; 25.1 L (2.2%) were used for a grey indication (volume resuscitation for hypovolaemia). CONCLUSIONS: The demand management programme provides surveillance of indications and retrospective verification of appropriate use. The majority of HAS indications were appropriate. Plasma exchange accounted for 84.6% of HAS usage and will be the focus of further demand management strategies. The demand management programme whilst aiming to promote best transfusion practice also ensures a tool to manage future shortages according to indication and available supply.

Risk of clinical deterioration in patients with lupus nephritis receiving rituximab.

Rituximab is a chimeric anti-CD20 monoclonal antibody that is used as an immunosuppressive agent in cyclophosphamide refractory lupus nephritis to induce remission. Although uncontrolled case series suggest efficacy, this is not yet supported by evidence from prospective randomized controlled trials. The objective of this retrospective case series is to report the clinical outcome of seven patients who received rituximab for lupus nephritis in a single centre between 2011 and 2014. One patient had clinical evidence of an uncomplicated response to therapy. A second patient responded well with the first rituximab course, but had transient worsening of renal function and nephrotic syndrome with a second course. The other five patients all had evidence of a clinical deterioration following rituximab. Two had transient worsening of both renal function and nephrotic syndrome, with subsequent evidence of response in one of these. A fifth patient showed evidence of worsening nephrotic syndrome and renal function which then improved but with renal function remaining below the level present before rituximab. A sixth developed rapidly progressive renal failure following rituximab with active nephritis on renal biopsy and required rescue therapy with high dose steroids and cyclophosphamide. A seventh developed a transient worsening of her nephrotic syndrome and an exacerbation of extrarenal symptoms following rituximab. The two patients showing a good response had complete B cell depletion and incomplete depletion may be a factor in the deterioration seen in the other patients. Our experience suggests that rituximab therapy in lupus nephritis is not without risk and patients should be informed of this beforehand. This is particularly important in view of the uncertainty that rituximab will offer a therapeutic benefit.

Proposal for Classification of the Great Saphenous Vein Aplasia by the B-mode Ultrasound.

BACKGROUND: The lack of the great saphenous vein (GSV) in its compartment is rarely mentioned in literature, although it happens in individuals with or without insufficiency of it. With the help of the B-mode ultrasound examination this vein can be easily identified. The aim of this study was to propose a classification for the findings. METHODS: Prospective study carried out for a period of 6 months in a sample of 2,665 lower limbs with ages ranging from 17 to 85, being that 1,286 patients are female. These patients underwent B-mode ultrasound examination as recommended by the literature. This evaluation determined whether there was a GSV aplasia by the analysis of its location in the saphenous compartment. RESULTS: After images were taken they were classified as: type I-aplasia only along the thigh, type II-aplasia only along the calf, type III-aplasia in the distal section of the thigh and proximal calf, type IV-vein in the saphenous compartment in the thigh and aplasia in the whole calf, type V-vein in the saphenous compartment only in a short segment in the proximal thigh, and type VI-vein with short segment in the saphenous compartment in the distal calf. From the total of 2,665 limbs, aplasia was found in 442 (16.6%). CONCLUSIONS: These anatomic findings attain an important role in daily practice, influencing the surgical decision, particularly with the arrival of endovascular procedures, such as the use of laser and thermoablation.

Texture analysis of (125)I-A5B7 anti-CEA antibody SPECT differentiates metastatic colorectal cancer model phenotypes and anti-vascular therapy response.

BACKGROUND: We aimed to test the ability of texture analysis to differentiate the spatial heterogeneity of (125)I-A5B7 anti-carcinoembryonic antigen antibody distribution by nano-single photon emission computed tomography (SPECT) in well-differentiated (SW1222) and poorly differentiated (LS174T) hepatic metastatic colorectal cancer models before and after combretastatin A1 di-phosphate anti-vascular therapy. METHODS: Nano-SPECT imaging was performed following tail vein injection of 20 MBq (125)I-A5B7 in control CD1 nude mice (LS174T, n=3 and SW1222, n=4), and CA1P-treated mice (LS174T, n=3; SW1222, n=4) with liver metastases. Grey-level co-occurrence matrix textural features (uniformity, homogeneity, entropy and contrast) were calculated in up to three liver metastases in 14 mice from control and treatment groups. RESULTS: Before treatment, the LS174T metastases (n=7) were more heterogeneous than SW1222 metastases (n=12) (uniformity, P=0.028; homogeneity, P=0.01; contrast, P=0.045). Following CA1P, LS174T metastases (n=8) showed less heterogeneity than untreated LS174T controls (uniformity, P=0.021; entropy, P=0.006). Combretastatin A1 di-phosphate-treated SW1222 metastases (n=11) showed no difference in texture features compared with controls (all P>0.05). CONCLUSIONS: Supporting the potential for novel imaging biomarkers, texture analysis of (125)I-A5B7 SPECT shows differences in spatial heterogeneity of antibody distribution between well-differentiated (SW1222) and poorly differentiated (LS174T) liver metastases before treatment. Following anti-vascular treatment, LS174T metastases, but not SW1222 metastases, were less heterogeneous.

Conditions for high yield of selective-area epitaxy InAs nanowires on SiO x /Si(111) substrates.

Experimental data and a model are presented which define the boundary values of V/III flux ratio and growth temperature for droplet-assisted nucleation of InAs semiconductor nanowires in selective-area epitaxy on SiO(x)/Si (111) substrates by molecular beam epitaxy. Within these boundaries, the substrate receives a balanced flux of group III and V materials allowing the growth of vertically oriented nanowires as compared to the formation of droplets or crystallites.

Maternal sepsis incidence, aetiology and outcome for mother and fetus: a prospective study.

OBJECTIVE: To determine the incidence of maternal bacteraemia during pregnancy and for 6 weeks postpartum, describe the gestation/stage at which sepsis occurs, the causative microorganisms, antibiotic resistance and review maternal, fetal and neonatal outcome. DESIGN: Prospective review. SETTING: Two tertiary referral, maternity hospitals in Dublin, Ireland. POPULATION: During 2005-2012 inclusive, 150 043 pregnant women attended and 24.4% of infants born in Ireland were delivered at the hospitals. METHODS: Demographic, clinical, microbiological and outcome data was collected from women with sepsis and compared with controls. MAIN OUTCOME MEASURES: Incidence, bacterial aetiology, gestation/stage at delivery, mode of delivery, antibiotic resistance, admission to augmented care, maternal, fetal and neonatal outcome. RESULTS: The sepsis rate was 1.81 per 1000 pregnant women. Escherichia coli was the predominant pathogen, followed by Group B Streptococcus. Sepsis was more frequent among nulliparous women (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.07-1.79) and multiple births (OR 2.04; 95% CI 0.98-4.08). Seventeen percent of sepsis episodes occurred antenatally, 36% intrapartum and 47% postpartum. The source of infection was the genital tract in 61% (95% CI 55.1-66.6) of patients and the urinary tract in 25% (95% CI 20.2-30.5). Sepsis was associated with preterm delivery (OR 2.81; 95% CI 1.99-3.96) and a high perinatal mortality rate (OR =5.78; 95% CI 2.89-11.21). Almost 14% of women required admission to augmented care. The most virulent organisms were Group A Streptococcus linked to postpartum sepsis at term and preterm Escherichia coli sepsis. CONCLUSIONS: Maternal sepsis is associated with preterm birth, a high perinatal mortality rate and nulliparous women.

Cupuassu (Theobroma grandiflorum) pulp, probiotic, and prebiotic: Influence on color, apparent viscosity, and texture of goat milk yogurts.

Cupuassu is an acidic fruit that has a characteristic aroma, flavor, and texture; its fiber-rich pulp can provide a different consistency than other fruit pulps. Goat milk is an excellent source of amino acids, fatty acids, and minerals, and is widely used for processing fermented milks, such as yogurt. However, compared with cow milk yogurts, it is difficult to make goat milk yogurts with a good consistency. Therefore, it is necessary to use certain technological strategies. This study was carried out to investigate the possibility of adding cupuassu pulp, probiotic (Lactobacillus acidophilus LA-5), and prebiotic (inulin) to improve the texture of goat milk yogurt. A total of 6 treatments were performed: natural (N), probiotic (Pro), prebiotic (Pre), synbiotic (S), cupuassu (C), and probiotic with cupuassu (PC). The viability of probiotic in yogurts (Pro, S, and PC) was evaluated. In addition, instrumental analyses (pH, color, apparent viscosity, and texture) were performed to evaluate the influence of these different ingredients on goat milk yogurts. The probiotic bacteria remained viable (≥7 log cfu·mL(-1)) throughout the 28d of refrigerated storage, which exceeded the minimum count required to confer probiotic physiological benefits. The pH levels of the yogurts inoculated with L. acidophilus (Pro, S, and PC) were lower than others yogurts (N, Pre, and C). However, all yogurt samples underwent gradual decreases in pH until 7 to 14d of storage. The lightness (L*) was affected initially by addition of all ingredients (cupuassu pulp, probiotic, and prebiotic). The addition of cupuassu pulp (C and PC) increased the L* during the period of storage. Apparent viscosity and firmness decreased in the PC yogurt. The consistency was highest in the yogurts with added prebiotic (Pre and S) than the other yogurts (N, Pro, C, and PC) at the end of the storage period (d 28). The cohesiveness remained constant in all yogurts (N, Pro, Pre, S, C, and PC). Based on the results obtained from the current study, it was concluded that cupuassu pulp addition improves the texture of goat milk yogurts. Therefore, this pulp could be an important technological strategy for the dairy goat industry.