Heterogeneous integration of a III-V quantum dot laser on high thermal conductivity silicon carbide.

Heat accumulation prevents semiconductor lasers from operating at their full potential. This can be addressed through heterogeneous integration of a III-V laser stack onto non-native substrate materials with high thermal conductivity. Here, we demonstrate III-V quantum dot lasers heterogeneously integrated on silicon carbide (SiC) substrates with high temperature stability. A large T0 of 221 K with a relatively temperature-insensitive operation occurs near room temperature, while lasing is sustained up to 105°C. The SiC platform presents a unique and ideal candidate for realizing monolithic integration of optoelectronics, quantum, and nonlinear photonics.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Low loss (Al)GaAs on an insulator waveguide platform.

In this Letter, we demonstrate a low loss gallium arsenide and aluminum gallium arsenide on an insulator platform by heterogenous integration. The resonators on this platform exhibit record high quality factors up to 1.5×106, corresponding to a propagation loss ∼0.4 dB/cm. For the first time, to the best of our knowledge, the loss of integrated III-V semiconductor on insulator waveguides becomes comparable with that of the silicon-on-insulator waveguides. This Letter should have a significant impact on photonic integrated circuits (PICs) and become an essential building block for the evolving nonlinear PICs and integrated quantum photonic systems in the future.

A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42-12/BIG 2-12 SNAP trial.

Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Patients and methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: arm A, nab-paclitaxel 150 mg/m2 days 1 and 15 Q28; arm B, nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Q28; arm C, nab-paclitaxel 75 mg/m2 days 1, 8, 15 and 22 Q28. Induction was three cycles nab-paclitaxel 150/125 mg/m2, days 1, 8 and 15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared with the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life (QoL) evaluation was carried out, and the global indicator for physical well-being was defined as the primary QoL end point; completion rates of QoL forms were >90%. Results: In total, 255 patients were assessable for the primary end point. After 18.2-month median follow-up, 182 PFS events were observed. Median PFS was 7.9 months [90% confidence interval CI 6.8-8.4] in arm A, 9.0 months (90% CI 8.1-10.9) in arm B and 8.5 months (90% CI 6.7-9.5) in arm C. PFS in arm B was significantly longer than the historical reference of first-line docetaxel (P = 0.03). Grade ≥2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of the patients in arm A, B and C, respectively (Grade ≥3 in 9.1%, 5.6% and 6.6% of the patients, respectively). Noteworthy, the QoL scores for sensory neuropathy did not worsen with prolonged nab-paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225.

O-band electrically injected quantum dot micro-ring lasers on on-axis (001) GaP/Si and V-groove Si.

We report statistical comparisons of lasing characteristics in InAs quantum dot (QD) micro-rings directly grown on on-axis (001) GaP/Si and V-groove (001) Si substrates. CW thresholds as low as 3 mA and high temperature operation exceeding 80 °C were simultaneously achieved on the GaP/Si template template with an outer-ring radius of 50 µm and a ring width of 4 µm, while a sub-milliamp threshold of 0.6 mA was demonstrated on the V-groove Si template with a smaller cavity size of 5-µm outer-ring radius and 3-µm ring width. Evaluations were also made with devices fabricated simultaneously on native GaAs substrates over a significant sampling analysis. The overall assessment spotlights compelling insights in exploring the optimum epitaxial scheme for low-threshold lasing on industry standard Si substrates.

Monolithically integrated InAs/InGaAs quantum dot photodetectors on silicon substrates.

We report InAs/InGaAs quantum dot (QD) waveguide photodetectors (PD) monolithically grown on silicon substrates. A high-crystalline quality GaAs-on-Si template was achieved by aspect ratio trapping together with the combined effects of cyclic thermal annealing and strain-balancing layer stacks. An ultra-low dark current of 0.8 nA and an internal responsivity of 0.9 A/W were measured in the O band. We also report, to the best of our knowledge, the first characterization of high-speed performance and the first demonstration of the on-chip photodetection for this QD-on-silicon system. The monolithically integrated waveguide PD shares the same platform as the previously demonstrated micro-ring lasers and can thus be integrated with laser sources for power monitors or amplifiers for pre-amplified receivers.

Integrated optical driver for interferometric optical gyroscopes.

We present the first chip-scale "integrated optical driver" (IOD) that can interrogate with a sensing coil to realize an interferometric optical gyroscope. The chip comprises a light source, three photodiodes, two phase modulators and two 3-dB couplers within an area of 4.5 mm2. This allows for a significant reduction in size, weight, power consumption and cost of optical gyroscopes.

Electrically pumped continuous wave quantum dot lasers epitaxially grown on patterned, on-axis (001) Si.

High performance III-V lasers at datacom and telecom wavelengths on on-axis (001) Si are needed for scalable datacenter interconnect technologies. We demonstrate electrically injected quantum dot lasers grown on on-axis (001) Si patterned with {111} v-grooves lying in the [110] direction. No additional Ge buffers or substrate miscut was used. The active region consists of five InAs/InGaAs dot-in-a-well layers. We achieve continuous wave lasing with thresholds as low as 36 mA and operation up to 80°C.

Local paleoenvironmental controls on the carbon-isotope record defining the Bitter Springs Anomaly.

Large magnitude (>10‰) carbon-isotope (δ13 C) excursions recorded in carbonate-bearing sediments are increasingly used to monitor environmental change and constrain the chronology of the critical interval in the Neoproterozoic stratigraphic record that is timed with the first appearance and radiation of metazoan life. The ~10‰ Bitter Springs Anomaly preserved in Tonian-aged (1000-720 Ma) carbonate rocks in the Amadeus Basin of central Australia has been offered as one of the best preserved examples of a primary marine δ13 C excursion because it is regionally reproducible and δ13 C values covary in organic and carbonate carbon arguing against diagenetic exchange. However, here we show that δ13 C values defining the excursion coincide with abrupt lithofacies changes between regularly cyclic grainstone and microbial carbonates, and desiccated red bed mudstones with interbedded evaporite and dolomite deposits, recording local environmental shifts from restricted marine conditions to alkaline lacustrine and playa settings that preserve negative (-4‰) and positive (+6‰) δ13 C values, respectively. The stratigraphic δ13 C pattern in both organic and carbonate carbon recurs within the basin in a similar way to associated sedimentary facies, reflecting the linkage of local paleoenvironmental conditions and δ13 C values. These local excursions may be time transgressive or record a relative sea-level influence manifest through exposure of sub-basins isolated by sea-level fall below shallow sills, but are independent of secular seawater variation. As the shallow intracratonic setting of the Bitter Springs Formation is typical of other Neoproterozoic carbonate successions used to construct the present δ13 C seawater record, it identifies the potential for local influences on δ13 C excursions that are neither diagenetic nor representative of the global exogenic cycle.

Fully integrated microwave frequency synthesizer on heterogeneous silicon-III/V.

We demonstrate a photonic microwave generator on the heterogeneous silicon-InP platform. Waveguide photodiodes with a 3 dB bandwidth of 65 GHz and 0.4 A/W responsivity are integrated with lasers that tune over 42 nm with less than 150 kHz linewidth. Microwave signal generation from 1 to 112 GHz is achieved.

Breast cancer detection among Irish BRCA1 & BRCA2 mutation carriers: a population-based study.

BACKGROUND: High-risk breast cancer screening for BRCA1/2 mutation carriers with clinical breast exam, mammography and MRI has reported sensitivity of 100 %, but BRCA1/2 mutation carriers still present with interval cancers. AIMS: We investigated the presentation and screening patterns of an Irish cohort of BRCA1/2 mutation carriers with breast cancer. MATERIALS AND METHODS: BRCA1/2 mutation carriers with breast cancer were identified in this retrospective cohort study. Records were reviewed for BRCA1/2 mutation status, demographics, screening regimen, screening modality, stage and histology at diagnosis. RESULTS: Fifty-three cases of breast cancer were diagnosed between 1968 and 2010 among 60 Irish hereditary breast ovarian cancer (HBOC) families. In 50 of 53 women, the diagnosis of breast cancer predated the identification of BRCA1/2 mutations. Breast cancer detection method was identified in 47 % of patients (n = 25): 80 % (n = 20) by clinical breast exam (CBE), 12 % by mammography (n = 3), 8 % by MRI (n = 2). Fourteen women (26 %) developed a second breast cancer. Ten of these patients (71 %) were involved in regular screening; 50 % were detected by screening mammography, 20 % by MRI and 30 % by CBE alone. Six patients (43 %) had a change in morphology from first to second breast cancers. There was no change in hormone receptor status between first and second breast cancers. CONCLUSION: In this cohort of Irish BRCA1/2 mutation carriers, compliance with screening was inconsistent. There was a 30 % incidence of interval cancers occurring in women in high-risk screening. Preventive surgery may be a more effective risk reduction strategy for certain high-risk women.

Micro-trace fossils reveal pervasive reworking of Pliocene sapropels by low-oxygen-adapted benthic meiofauna.

Animal burrowers leave an indelible signature on the sedimentary record in most marine environments, with the seeming exception of low-oxygen environments. In modern sedimentary settings, however, sub-millimetre-sized benthic animals (meiofauna) are adapted to low oxygen and even sulfidic conditions. Almost nothing is known about their impact on ancient marine sediments because they leave few recognizable traces. Here we show, in classic Pliocene-aged anoxic facies from the Mediterranean, the first reported trace fossil evidence of meiofaunal activity and its relation to changing oxygenation. A novel approach utilizing electron imaging of ion-polished samples shows that meiofauna pervasively reworked sediment under oxygen-depleted conditions that excluded macrofauna, fragmenting organic laminae and emplacing 15- to 70-µm-diameter faecal pellets without macroscopically influencing the fabric. The extent of reworking raises the question: how pervasively altered are other sediments presently assumed to lack animal influence and how far into the geological record does this influence extend?

The cost of the inpatient management of febrile neutropenia in cancer patients--a micro-costing study in the Irish healthcare setting.

The objective was to evaluate the resource use and cost of hospitalisation for febrile neutropenia (FN) from the health-payer's perspective. This was a single centre study. Adults undergoing chemotherapy, who were admitted for FN, were identified prospectively. Patient medical records were reviewed retrospectively. Demographics and resource utilisation data were obtained from a cohort of 32 patients (69% female, mean age = 58.8 years). Twenty-five per cent of patients had more than one FN episode. In total, 42 FN episodes were captured; 60% of episodes had occurred within the first two cycles of chemotherapy. The bootstrap estimation was used to determine mean hospital length of stay (LOS) with standard deviation (±SD) and mean costs ± SD. The mean LOS was 7.3 ± 0.5 days. The mean cost per FN episode was €8915 ± 718. The major cost driver was hospital bed-stay (mean cost of €6851 ± 549). Other cost drivers included antibacterial treatment at €760 ± 156, laboratory investigations at €538 ± 47 and the requirement for blood bank products at €525 ± 189. To our knowledge, this is the first investigation of the cost of chemotherapy induced FN within the context of the Irish healthcare setting.

Patients over 65 years are assigned lower ECOG PS scores than younger patients, although objectively measured physical activity is no different.

OBJECTIVES: The Eastern Cooperative Group Performance Status (ECOG PS) is a widely used standard functional classification in oncology practice, the verbal descriptors of which refer to physical activity (PA). Little is known about the cut-off points of this scale and measured PA levels. This research investigated the relationship between PS assigned, objectively measured PA, and patient age. MATERIALS AND METHODS: One hundred ambulatory patients with treatment-naive cancer wore an accelerometer (RT3) for a mean (SD) of 5.6 (1.1) days before initial oncology evaluation and ECOG PS assignment. RESULTS: Seventy five participants (75%) were <65 years and 25 were ≥65 years. Eighty nine (89%) were assigned an ECOG PS of 0 or 1 and 11% a PS of 2 or 3. A weak but significant inverse association was found between objectively measured PA and PS (rho = -0.26, p = 0.01). Seventy one participants (80%) with a PS of 0 or 1 spent more than 50% of waking hours resting. Participants assigned a PS of 2-3 spent significantly more time resting than those assigned a PS of 0 (p = 0.01). Age ≥65 years was significantly related to PS assigned (p = 0.04), although the older cohort were no less sedentary than younger patients. CONCLUSION: PA levels were low, but PS scoring reflected relative PA levels and differentiated between patients of PS 0 and 2-3. Chronological age was not predictive of activity levels, but older patients were assigned lower PS scores. Incorporation of objective PA measures may merit further investigation especially in the geriatric oncology setting.

Testing the 'teachable moment' premise: does physical activity increase in the early survivorship phase?

PURPOSE: Little is known about objectively measured physical activity during the early survivorship period. This study measured physical activity, fatigue, and quality of life (QOL) in breast cancer patients over the first year after completion of chemotherapy and compared results to a matched non-cancer group. METHODS: Data was obtained from 24 breast cancer subjects (mean ± SD) 50.9 ± 12.8 years at time points of 6 weeks, 6 months and 1 year after completion of adjuvant chemotherapy and from 20 matched women. The following variables were assessed, physical activity (RT3 accelerometer and International Physical Activity Questionnaire), quality-of-life (EORTC QLQ C-30) and fatigue (Brief Fatigue Inventory). RESULTS: At 6 weeks after completion of chemotherapy, high levels of sedentary behaviour were found (6.8 ± 1.9 h sedentary per day), which did not improve, and was no different to the comparison group (6.5 ± 1.4 h). Less light activity was performed in the cancer cohort compared to the comparison group (p = 0.003). Body mass index (BMI) increased significantly in the cancer cohort (p = 0.015) and 1 year after chemotherapy finished only 13% (n = 3) had a BMI <25, while the comparable value was 45% (n = 9) in the non-cancer group. The QOL domain of cognitive function improved over the first 6 months (p = 0.034) but physical functioning declined (p = 0.008) over this time period. Fatigue did not change, and at the 1-year time point, 38% of the cancer patients (n = 11) reported high levels of fatigue. CONCLUSION: This study highlighted the unchanging sedentary behaviour and weight gain of breast cancer survivors during the first year after completion of chemotherapy, which may inform rehabilitation models in this population.

Incidental detection of colorectal malignancies using FDG PET-CT.

The aim of this study was to evaluate the detection rate of incidental colorectal malignancies using whole-body 18FDG-PET/CT at an Irish teaching hospital. We performed a retrospective review of the records of 800 consecutive patients undergoing PET-CT scans at our institution from January 2009 - August 2009. The radiologic reports were analysed and all scans with focal colonic FDG uptake were audited. The colonoscopic and histologic records of the patients who underwent further investigation were reviewed for cancerous and pre-cancerous histology. A total of 643 patients were included in the study. Forty-eight patients (7.5%) had scans which demonstrated focal colonic FDG uptake. Of the 21 patients who underwent further investigation with endoscopy, 14 (66.7%) had biopsies which were positive for dysplasia, this represented 2.2% of the total patients undergoing PET-CT. Eight of these fourteen patients (1.2% of the total) had biopsies demonstrating adenocarcinoma. Four of these patients (50%) had TNM stage 1 or 2 colorectal carcinoma and underwent subsequent curative surgical resection. We found a 2.2% rate of incidentally-diagnosed colorectal malignant and premalignant lesions in patients undergoing PET-CT at our institution. A 1.2% rate of adenocarcinoma was identified. This rate is higher than previously described in the literature.

Optimally tolerated dose of lapatinib in combination with docetaxel plus trastuzumab in first-line treatment of HER2-positive metastatic breast cancer.

BACKGROUND: This phase IB, open-label, dose-escalation study evaluated the safety, tolerability, and optimally tolerated regimen (OTR) of lapatinib in combination with docetaxel and trastuzumab in patients with previously untreated stage IV metastatic breast cancer (MBC) tumors overexpressing human epidermal growth factor receptor 2 (HER2). PATIENTS AND METHODS: Evaluated dose regimens included lapatinib (500-1500 mg/day), docetaxel (triweekly; 60-100 mg/m²), and trastuzumab (weekly; 2 mg/kg fixed dose); prophylactic granulocyte colony-stimulating factor was included with regimens with ≥750 mg/day lapatinib. End points included OTR and safety/tolerability (primary), overall response rate (ORR), and pharmacokinetics (secondary). RESULTS: None of the patients (N = 53) experienced dose-limiting toxic effects (DLTs) at the highest dose level; thus, the OTR of lapatinib with 100 mg/m(2) docetaxel was not determined. Common adverse events included diarrhea, nausea, alopecia, fatigue, and rash; grade 3/4 (≥2 patients) were neutropenia, diarrhea, leukopenia, peripheral neuropathy, and rash. Seven patients had DLTs (cycle 1). In 45 patients with measurable disease confirmed by bone scan, investigator-assessed ORR was 31%; without bone scan, confirmation was 64%; 8 patients without measurable disease were evaluated as stable. Lapatinib/docetaxel plasma concentrations were positively associated with complete response. CONCLUSIONS: Lapatinib/docetaxel/trastuzumab is a feasible and well-tolerated treatment of untreated HER2-positive stage IV MBC. Two lapatinib/docetaxel OTR doses were recommended (1250 mg/75 mg/m²; 1000 mg/100 mg/m²). CLINICAL TRIAL NUMBER: NCT00251433.

Feasibility and efficacy of a supervised exercise intervention in de-conditioned cancer survivors during the early survivorship phase: the PEACH trial.

PURPOSE: This study aims to evaluate the feasibility and efficacy of an 8-week supervised exercise program in de-conditioned cancer survivors within 2-6 months of chemotherapy completion. METHODS: Participants were randomly assigned to an 8-week, twice-weekly, supervised aerobic exercise training regime (n = 23) or a usual care group (n = 20). Feasibility was assessed by recruitment rate, program adherence and participant feedback. The primary outcome was aerobic fitness assessed by the Modified Bruce fitness test at baseline (0 weeks), post-intervention (8 weeks) and at 3-month follow-up. Secondary outcomes included physical activity, waist circumference, fatigue and quality of life. RESULTS: The recruitment rate was 81 % and adherence to the supervised exercise was 78.3 %. Meaningful differences in aerobic fitness between the exercise and usual care groups at both the 8-week [mean 3.0 mL kg(-1) min(-1) (95 % CI -1.1-7.0)] and 3-month follow-up [2.1 mL kg(-1) min(-1) (-2.3-6.6)] were found, although these differences did not achieve statistical significance (p values >0.14). Self-reported physical activity increased in the exercise group (EG) compared to the usual care group at both 8-week (p = 0.01) and 3-month follow-up (p = 0.03) and significant differences in favour of the EG were found for physical well-being at both the 8-week (p = 0.03) and 3-month follow-up (p = 0.04). Improvements in fatigue (p = 0.01), total quality of life plus fatigue (p = 0.04), and a composite physical functioning score (p = 0.01) at the 3-month follow-up were also found. CONCLUSION: The PEACH trial suggests that 8 weeks of supervised aerobic exercise training was feasible and may improve aerobic fitness, fatigue and quality of life in de-conditioned cancer survivors during the early survivorship phase. IMPLICATIONS FOR CANCER SURVIVORS: Exercise interventions commenced in the early survivorship phase appear safe, feasible and may lead to improvements in QOL and fatigue.

The effect of aerobic exercise on metabolic and inflammatory markers in breast cancer survivors--a pilot study.

PURPOSE: Physical activity is associated with a reduced risk of breast cancer development and recurrence. There are several hypothesised mechanisms for this including positive effects on metabolic and inflammatory biomarkers and favourable changes in anthropometric variables. This pilot study examined the effect of an 8-week aerobic exercise intervention on several of these outcomes, including body composition, the metabolic syndrome, C-reactive protein (CRP) and physical activity, in breast cancer survivors 2-6 months post-chemotherapy. METHODS: Assessments were completed at baseline, at 8-weeks and 3-months post-intervention. Measures taken following a 12-h fast included body composition (bioimpedance analysis), metabolic syndrome (waist circumference, blood pressure, high-density lipoprotein cholesterol, triglycerides and fasting glucose), insulin resistance (homeostatic model assessment), CRP and physical activity (accelerometry and questionnaire). Participants were randomized to either an 8-week moderate-intensity aerobic exercise group or a usual-care control group. Analysis was completed using repeated-measures analysis of variance (ANOVA) (p = 0.05). RESULTS: Twenty-six breast cancer survivors participated (mean (standard deviation) age 48.1 (8.8) years, exercise group; n = 16, control group; n = 10). At baseline, 13 participants were overweight, 6 were obese and 19 centrally obese. Intention-to-treat analysis revealed no significant differences between the exercise and control groups in any of the outcomes measures; however, analysis of those who adhered to >90 % of the supervised exercise class showed a significant decrease in waist circumference (p = 0.05) and a significant increase in subjectively reported "total weekly" (p = 0.005) activity. CONCLUSION: While this 8-week aerobic exercise pilot intervention did not elicit significant improvements in biomarkers of breast cancer risk, there was some suggestion of improvements in waist circumference and subjectively measured physical activity in participants with >90 % adherence to the programme. A trial of longer duration and greater subject numbers is warranted.