Soliton Based Dynamic Nuclear Polarization: An Overhauser Effect in Cyclic Polyacetylene at High Field and Room Temperature.

Polyacetylene, a versatile material with an electrical conductivity that can span 7 orders of magnitude, is the prototypical conductive polymer. In this letter, we report the observation of a significant Overhauser effect at the high magnetic field of 14.1 T that operates at 100 K and room temperature in both linear and cyclic polyacetylene. Significant NMR signal enhancements ranging from 24 to 45 are obtained. The increased sensitivity enabled the characterization of the polymer chain defects at natural abundance. The absence of end methyl group carbon-13 signals provides proof of the closed-loop molecular structure of cyclic polyacetylene. The remarkable efficiency of the soliton based Overhauser effect DNP mechanism at high temperature and high field holds promise for applications and extension to other conductive polymer systems.

The value of case reports in rare oncological scenarios: mixed method analysis of colorectal metastases from breast cancer.

With improved survival of cancer patients, we increasingly encounter infrequent metastatic locations. While for the common metastatic locations both prognostic information as well as evidence-based guidelines are available, for rare locations we have to rely on anecdotal case reports, the value of which is currently unknown. Therefore, we performed a systemic literature review and compare the results with a large national real-life cohort focussed on breast cancer patients with colorectal metastases. We performed a systematic literature search for breast cancer patients with colorectal metastases. Autopsy studies were excluded. Data on stage, histological factors, treatment and outcome were extracted. All identified cases were analysed as individual patients. The real-life cohort was extracted from the nationwide Dutch pathology databank. Linkage with the Netherlands Cancer Registry provided clinical characteristics, treatment and outcome data. Survival analyses and univariate regression were performed to identify relevant features for future treatment decisions. We identified 308 patients from 207 studies in the literature, and 454 patients in the real-life cohort. Colorectal metastases were the first metastatic event in 42.5% and 47.0% respectively. Cohorts were comparable for age, gender, location and hormone status, but differed in tumour type, stage and treatment. The time to colorectal metastases was similar in both cohorts (median of 68 months), and was dependent on presence of other metastases, nodal status, and primary breast surgery. The median overall survival after development of colorectal metastases was 20.6 months (95%CI 18.0-23.1 months). Despite a potential publication bias and lack of complete data for patients in the case report series, we have shown that an extensive systematic review can provide data that are comparable to real-life data, which can be used for decision-making and informing patients. Colorectal metastases are a late event in breast cancer patients, that is not associated with a detrimental survival.

Painful lower limb nodules as first symptom of resectable pancreatic acinar cell cancer: a case report.

BACKGROUND: Pancreatic panniculitis is characterized by subcutaneous fat necrosis and is a rare presentation of an underlying pancreatic disease, appearing in approximately 2-3% of all patients with a pancreatic disease. The nodules usually involve the lower extremities. Pancreatic panniculitis is commonly associated with acute or chronic pancreatitis, and occasionally with pancreatic cancer, especially acinar cell carcinoma. CASE PRESENTATION: A 77-year-old Caucasian woman with no significant medical history was referred to our center with multiple painful, itchy, and warm red/blue cutaneous nodules on the left lower leg. These skin lesions were consistent with the clinical diagnosis of panniculitis. The skin biopsy obtained showed a predominantly lobular panniculitis with fat necrosis of which the aspect was highly suspicious for pancreatic panniculitis. Further analysis revealed high lipase serum of > 3000 U/L (normal range < 60 U/L), and on computed tomography scan a mass located between the stomach and the left pancreas was seen. Endoscopic ultrasonography-guided fine-needle biopsy confirmed the diagnosis of acinar cell carcinoma. After discussing the patient in the pancreatobiliary multidisciplinary team meeting, laparoscopic distal pancreatectomy including splenectomy and en bloc wedge resection of the stomach due to tumor in-growth was performed. The cutaneous nodules on both legs disappeared 1-2 days after surgery. No long-term complications were reported during follow-up. One year after surgery, the patient presented with similar symptoms as preoperatively. Computed tomography scan showed local recurrence and distal metastases, which were subsequently confirmed by biopsy. She started with palliative folinic acid-fluorouracil-irinotecan-oxaliplatin chemotherapy but stopped after two cycles because of disease progression. The patient died 2 months later, 13 months after surgical resection. CONCLUSION: This case illustrates the importance of clinically recognizing cutaneous nodules and pathological recognizing the specific microscopic changes as sign of a (malignant) pancreatic disease.

Efficient and fabrication error tolerant grating couplers on the InP membrane on silicon platform.

In order to couple light between photonic integrated circuits and optical fibers, grating couplers are commonly employed. This paper describes the design and fabrication of deep and shallow-etched grating couplers with a metal back-reflector with record low insertion losses in InP-based platforms. The measured insertion losses for deep and shallow-etched gratings are 2.4 and 2.6 dB, respectively. Additionally, fabrication error tolerances in shallow etched grating couplers have been examined experimentally, which showed high tolerance of this structure toward the grating period and fill factor.

Quantum dynamics of Mn2+ in dimethylammonium magnesium formate.

Dimethylammonium magnesium formate, [(CH3)2NH2][Mg(HCOO)3] or DMAMgF, is a model used to study high temperature hybrid perovskite-like dielectrics. This compound displays an order-disorder phase transition at about 260 K. Using multifrequency electron spin resonance in continuous wave and pulsed modes, we herein present the quantum dynamics of the Mn2+ ion probe in DMAMgF. In the high temperature paraelectric phase, we observe a large distribution of the zero field splitting that is attributed to the high local disorder and further supported by density functional theory computations. In the low temperature ferroelastic phase, a single structure phase is detected and shown to contain two magnetic structures. The complex electron paramagnetic resonance signals were identified by means of the Rabi oscillation method combined with the crystal field kernel density estimation.

The value of MRI STIR signal intensity on return to play prognosis and reinjury risk estimation in athletes with acute hamstring injuries.

OBJECTIVES: Previous studies have shown low to moderate evidence for a variety of magnetic resonance imaging (MRI) features as prognostic factors in athletes with hamstring injuries. Short-tau inversion recovery (STIR) signal intensity has not yet been investigated for assessing the prognosis of acute muscle injuries. Our aim was to explore the relationship between MRI STIR signal intensity and time to return to play (RTP) and to investigate the association between MRI STIR and reinjury risk in athletes with acute hamstring injuries. STUDY DESIGN: Case-control study. METHODS: We used MRI STIR to measure intramuscular signal intensity in patients with clinically diagnosed hamstring injuries at two time points: at injury and RTP. At injury, we calculated the association of MRI STIR signal intensity with the time to RTP and reinjury risk. At RTP, the association of MRI STIR signal intensity and reinjury risk and the change in MRI STIR signal intensity over time on reinjury risk was evaluated. RESULTS: 51 patients were included. We found increased MRI STIR signal intensity: (1) at time of injury not to be associated with time to RTP, (2) at time of injury to be associated with a slightly lower risk for reinjury: odds 0.986 (0.975-0.998, p=0.02) and (3) at RTP not to be associated with reinjury risk. (4) We found no association between the change in MRI STIR signal intensity over time and reinjury risk. CONCLUSION: Increased MRI STIR signal intensity at injury has no value in time to RTP prognosis, but is associated with a reduced reinjury risk.

Characterizing landfill leachate migration potential of a semi-arid duplex soil.

Leachate migration from open landfills is an environmental concern of developing cities. This study investigated the base soil-profile pedo-physical and chemical properties of the South African Sepane soil form or referred to as Cutanic Luvisol at the Bloemfontein southern landfill under the Mangaung municipality in the Free State Province. Six soil-profiles pedo-physical, exchangeable-cations and heavy metals concentrations were characterized from in-situ, core and loose soil-samples. The DTPA Test from a 5g air-dried soil extracted heavy metals. The soil profile was characterized by a layered Orthic-A, pedocutanic B- and C-horizons with lower horizons containing mean-total clay of 72%, bulk-density (≥1.5 gcm-3) and saturated hydraulic-conductivity (Ks < 6mmhr-1). Mean soil pH increased with depth from 6.4 to 6.8 along-side exchangeable-cations ranging from 19 to 2573 mgkg-1 in the order Ca > Mg > K > Na > S > P and Ca > Mg > Na > K > S > P for the respective A- and B-horizons. The Mg/K and (Ca + Mg)/K exceeded norm ratios. Soil-profile horizons had respective 44%, 34% and 22% heavy-metal distribution with mean content range of 0.001-37.3 mgkg-1 in the order Mn > Fe > Cr > Zn > Cu > As > Pb > Ni > Cd and Fe > Mn > Cr > Cu > As > Pb > Zn > Ni > Cd for the surface and subsurface horizons, respectively. Heavy-metal mean concentrations were below the norm except for Cr that was higher than 150% from upper horizons and posed serious risk to the near-surface environment. Soil profiles heavy-metal content and pollution-index was unpolluted (0.3-0.4), decreased with depth and reflected no subsurface pollution concerns. This study findings highlighted low internal-migration potential of clay soils and the need for understanding the sources and mode of migration of Cr at the landfill alongside continued monitoring.

Platelet-Rich plasma Injection Management for Ankle osteoarthritis study (PRIMA): protocol of a Dutch multicentre, stratified, block-randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Platelet-rich plasma (PRP) is a potentially efficacious treatment for ankle osteoarthritis (OA), but its use has not been examined in high-quality studies. Systematic reviews show that PRP injections significantly decrease pain and improve function in patients with knee OA. Ankle OA is more common than hip or knee OA in the young active population; with a prevalence of 3.4%.PRP injections in ankle OA are shown to be safe and improve quality of life over time, but no randomised controlled trial has been conducted. Our randomised controlled trial will evaluate the efficacy of PRP injections for symptom reduction and functional improvement, compared with placebo, in the treatment of ankle (talocrural) OA. METHODS AND ANALYSIS: We will conduct the Platelet-Rich plasma Injection Management for Ankle OA study: a multicentre, randomised, placebo-controlled trial. One hundred patients suffering from ankle OA will be randomised into two treatment groups: PRP injection or placebo (saline) injection. Both groups will receive two injections of PRP or placebo at an interval of 6 weeks. Primary outcome is the American Orthopaedic Foot and Ankle Society score at 26 weeks. Secondary outcomes determined at several follow-up moments up to 5 years, include Ankle Osteoarthritis Score, Foot and Ankle Outcome Score, pain subscale of (0-40), Visual Analogue Scale score (0-100), Ankle Activity Score (0-10), subjective patient satisfaction Short Form Health Survey-36, Global Attainment Scaling and the EuroQol-5 dimensions-3 levels utility score. A cost-effectiveness analysis will be performed at 1 year. ETHICS AND DISSEMINATION: The study is approved by the Medical Ethics Review Committee Amsterdam Medical Center, the Netherlands (ABR 2018-042, approved 23 July 2018) and registered in the Netherlands trial register (NTR7261). Results and new knowledge will be disseminated through the Dutch Arthritis Association (ReumaNederland), Dutch patient federation, conferences and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER: NTR7261.

Unconventional Field-Induced Spin Gap in an S=1/2 Chiral Staggered Chain.

We investigate the low-temperature magnetic properties of the molecule-based chiral spin chain [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O (pym=pyrimidine). Electron-spin resonance, magnetometry and heat capacity measurements reveal the presence of staggered g tensors, a rich low-temperature excitation spectrum, a staggered susceptibility, and a spin gap that opens on the application of a magnetic field. These phenomena are reminiscent of those previously observed in nonchiral staggered chains, which are explicable within the sine-Gordon quantum-field theory. In the present case, however, although the sine-Gordon model accounts well for the form of the temperature dependence of the heat capacity, the size of the gap and its measured linear field dependence do not fit with the sine-Gordon theory as it stands. We propose that the differences arise due to additional terms in the Hamiltonian resulting from the chiral structure of [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O, particularly a uniform Dzyaloshinskii-Moriya coupling and a fourfold periodic staggered field.

Correction to: Planning comparison of five automated treatment planning solutions for locally advanced head and neck cancer.

Following publication of the original article [1], the authors reported that one of the authors' names was processed incorrectly.

Planning comparison of five automated treatment planning solutions for locally advanced head and neck cancer.

BACKGROUND: Automated treatment planning and/or optimization systems (ATPS) are in the process of broad clinical implementation aiming at reducing inter-planner variability, reducing the planning time allocated for the optimization process and improving plan quality. Five different ATPS used clinically were evaluated for advanced head and neck cancer (HNC). METHODS: Three radiation oncology departments compared 5 different ATPS: 1) Automatic Interactive Optimizer (AIO) in combination with RapidArc (in-house developed and Varian Medical Systems); 2) Auto-Planning (AP) (Philips Radiation Oncology Systems); 3) RapidPlan version 13.6 (RP1) with HNC model from University Hospital A (Varian Medical Systems, Palo Alto, USA); 4) RapidPlan version 13.7 (RP2) combined with scripting for automated setup of fields with HNC model from University Hospital B; 5) Raystation multicriteria optimization algorithm version 5 (RS) (Laboratories AB, Stockholm, Sweden). Eight randomly selected HNC cases from institution A and 8 from institution B were used. PTV coverage, mean and maximum dose to the organs at risk and effective planning time were compared. Ranking was done based on 3 Gy increments for the parallel organs. RESULTS: All planning systems achieved the hard dose constraints for the PTVs and serial organs for all patients. Overall, AP achieved the best ranking for the parallel organs followed by RS, AIO, RP2 and RP1. The oral cavity mean dose was the lowest for RS (31.3 ± 17.6 Gy), followed by AP (33.8 ± 17.8 Gy), RP1 (34.1 ± 16.7 Gy), AIO (36.1 ± 16.8 Gy) and RP2 (36.3 ± 16.2 Gy). The submandibular glands mean dose was 33.6 ± 10.8 Gy (AP), 35.2 ± 8.4 Gy (AIO), 35.5 ± 9.3 Gy (RP2), 36.9 ± 7.6 Gy (RS) and 38.2 ± 7.0 Gy (RP1). The average effective planning working time was substantially different between the five ATPS (in minutes): < 2 ± 1 for AIO and RP2, 5 ± 1 for AP, 15 ± 2 for RP1 and 340 ± 48 for RS, respectively. CONCLUSIONS: All ATPS were able to achieve all planning DVH constraints and the effective working time was kept bellow 20 min for each ATPS except for RS. For the parallel organs, AP performed the best, although the differences were small.

Frequency-Swept Integrated and Stretched Solid Effect Dynamic Nuclear Polarization.

We investigate a new time domain approach to dynamic nuclear polarization (DNP), the frequency-swept integrated solid effect (FS-ISE), utilizing a high power, broadband 94 GHz (3.35 T) pulse EPR spectrometer. The bandwidth of the spectrometer enabled measurement of the DNP Zeeman frequency/field profile that revealed two dominant polarization mechanisms, the expected ISE, and a recently observed mechanism, the stretched solid effect (S2E). At 94 GHz, despite the limitations in the microwave chirp pulse length (10 µs) and the repetition rate (2 kHz), we obtained signal enhancements up to ∼70 for the S2E and ∼50 for the ISE. The results successfully demonstrate the viability of the FS-ISE and S2E DNP at a frequency 10 times higher than previous studies. Our results also suggest that these approaches are candidates for implementation at higher magnetic fields.

Characteristics of acute groin injuries in the adductor muscles: A detailed MRI study in athletes.

Acute adductor injuries account for the majority of acute groin injuries; however, little is known about specific injury characteristics, which could be important for the understanding of etiology and management of these injuries. The study aim was to describe acute adductor injuries in athletes using magnetic resonance imaging (MRI). Male athletes with acute groin pain and an MRI confirmed acute adductor muscle injury were prospectively included. MRI was performed within 7 days of injury using a standardized protocol and a reliable assessment approach. 156 athletes presented with acute groin pain of which 71 athletes were included, median age 27 years (range 18-37). There were 46 isolated muscle injuries and 25 athletes with multiple adductor injuries. In total, 111 acute adductor muscle injuries were recorded; 62 adductor longus, 18 adductor brevis, 17 pectineus, 9 obturator externus, 4 gracilis, and 1 adductor magnus injury. Adductor longus injuries occurred at three main injury locations; proximal insertion (26%), intramuscular musculo-tendinous junction (MTJ) of the proximal tendon (26%) and the MTJ of the distal tendon (37%). Intramuscular tendon injury was seen in one case. At the proximal insertion, 12 of 16 injuries were complete avulsions. This study shows that acute adductor injuries generally occur in isolation from other muscle groups. Adductor longus is the most frequently injured muscle in isolation and in combination with other adductor muscle injuries. Three characteristic adductor longus injury locations were observed on MRI, with avulsion injuries accounting for three-quarters of injuries at the proximal insertion, and intramuscular tendon injury was uncommon.

Characteristics of acute groin injuries in the hip flexor muscles - a detailed MRI study in athletes.

Hip flexor injuries account for one-third of acute groin injuries; however, little is known about specific injury characteristics. The aims of this study were to describe acute hip flexor injuries using magnetic resonance imaging (MRI) in athletes with acute groin pain and to compare specific muscle injuries with reported injury situations. Male athletes with acute groin pain were prospectively and consecutively included during three sports seasons. MRI was performed within 7 days of injury using a standardized protocol and a reliable assessment approach. All athletes with an MRI confirmed acute hip flexor muscle injury were included. A total of 156 athletes presented with acute groin pain of which 33 athletes were included, median age 26 years (range 18-35). There were 16 rectus femoris, 12 iliacus, 7 psoas major, 4 sartorius, and 1 tensor fascia latae injury. Rectus femoris injuries primarily occurred during kicking (10) and sprinting (4), whereas iliacus injuries most frequently occurred during change of direction (5). In 10 (63%) rectus femoris injuries, tendinous injury was observed. The iliacus and psoas major injuries were mainly observed at the musculotendinous junction (MTJ), and two included tendinous injury. We have illustrated specific injury locations within these muscles, which may be relevant for the clinical diagnosis and prognosis of these injuries. Most proximal rectus femoris injuries included tendinous injury. In contrast, distinct acute iliacus and psoas injuries predominantly occurred at the MTJ. Only the iliacus or psoas major were injured during change of direction, whereas rectus femoris injuries occurred primarily during kicking and sprinting.

Symmetry Reduction in the Quantum Kagome Antiferromagnet Herbertsmithite.

Employing complementary torque magnetometry and electron spin resonance on single crystals of herbertsmithite, the closest realization to date of a quantum kagome antiferromagnet featuring a spin-liquid ground state, we provide novel insight into different contributions to its magnetism. At low temperatures, two distinct types of defects with different magnetic couplings to the kagome spins are found. Surprisingly, their magnetic response contradicts the threefold symmetry of the ideal kagome lattice, suggesting the presence of a global structural distortion that may be related to the establishment of the spin-liquid ground state.

Skeletal Muscle Quality is Associated with Worse Survival After Pancreatoduodenectomy for Periampullary, Nonpancreatic Cancer.

BACKGROUND: Body composition measures may predict outcomes of cancer surgery. Whereas low muscle mass shown on preoperative computed tomography (CT) scans has been associated with worse outcomes after surgery for pancreatic cancer, less consideration has been given to low muscle attenuation, reflecting poor muscle quality. Studies relating muscle mass and muscle attenuation with outcomes for patients with periampullary, nonpancreatic cancer are lacking. METHODS: Skeletal muscle mass and attenuation were assessed in 166 consecutive patients undergoing pancreatoduodenectomy (PD) for periampullary, nonpancreatic cancer at a single center between 2000 and 2012. The skeletal muscle index (SMI) was calculated from cross-sectional muscle area on preoperative CT imaging at the third lumbar vertebra level (L3) and normalized for height. The skeletal muscle attenuation index (MAI) was calculated by measuring the average Hounsfield units of the total muscle area at the L3 level. Overall survival (OS) and the rate of major postoperative complications (Clavien-Dindo ≥3) were extracted from prospectively maintained databases. RESULTS: Low SMI was present in 78.3 % and low MAI in 48.8 % of the patients. The multivariate analysis showed lymph node metastasis [hazard ratio (HR) 1.8; 95 % confidence interval (CI) 1.1-2.9], microscopic radicality (HR 2.0; 95 % CI 1.2-3.4), and low MAI (HR 2.0; 95 % CI 1.2-3.3), but not low SMI to be significantly associated with decreased OS. Low MAI (HR 1.9; 95 % CI 1.0-3.8) was the only independent risk factor for major postoperative complications. CONCLUSION: Skeletal muscle quality, but not muscle mass, predicted survival and major complications after PD for periampullary, nonpancreatic cancer. Preoperative CT-derived body composition measures may stratify patients into risk categories and support shared decision making.

Interseason variability of a functional movement test, the 9+ screening battery, in professional male football players.

BACKGROUND: The Nine Plus screening battery test (9+) is a functional movement test intended to identify limitations in fundamental movement patterns predisposing athletes to injury. However, the interseason variability is unknown. AIM: To examine the variability of the 9+ test between 2 consecutive seasons in professional male football players. METHODS: Asymptomatic Qatar Star League players (n=220) completed the 9+ at the beginning of the 2013 and 2014 seasons. Time-loss injuries in training and matches were obtained from the Aspetar Injury and Illness Surveillance Program. No intervention was initiated between test occasions. RESULTS: A significant increase in the mean total score of 1.6 points (95% CI 1.0 to 2.2, p<0.001) was found from season 1 (22.2±4.1 (SD)) to season 2 (23.8±3.3). The variability was large, as shown by an intraclass correlation coefficient (ICC) of 0.24 (95% CI 0.11 to 0.36) and a minimal detectable change (MDC) of 8.7 points. Of the 220 players, 136 (61.8%) suffered a time-loss injury between the 2 tests. There was an improvement in mean total scores in the injured (+2.0±0.4 (SE), p<0.001) group but not in the uninjured group (+0.9±0.5, p=0.089). The variability from season 1 to season 2 was large both in the injured (ICC 0.25, 0.09 to 0.40, MDC 8.3) and uninjured (ICC 0.24, 0.02 to 0.43, MDC 9.1) groups. CONCLUSIONS: The 9+ demonstrated substantial intraindividual variability in the total score between 2 consecutive seasons, irrespective of injury. A change above 8 points is necessary to represent a real change in the 9+ test between seasons.

Taxonomy and molecular phylogeny of the Platystictidae of Sri Lanka (Insecta: Odonata).

The 22 Sri Lankan representatives of the family Platystictidae, all endemic to the island and belonging to the distinct endemic subfamily Platystictinae, are revised, and a new reconstruction of the phylogeny based on molecular characters is provided. Five new species are described: Ceylonosticta venusta sp. nov. (holotype ♂: Rambodde Falls, at the tunnel; Nuwara Eliya District, Central Province; N7.0489, E80.6961; 12-vii-2012; to be deposited at National Museum of Natural History, Colombo, Sri Lanka), C. inferioreducta sp. nov. (holotype ♂: Norton Bridge, stream on the B43 road 1.5km WNW of Norton Bridge; Nuwara Eliya District, Central Province; N6.9171, E80.5075; 28-vii-2009; to be deposited at National Museum of Natural History, Colombo, Sri Lanka), C. mirifica sp. nov. (holotype ♂: Uwella, primary forest on the road Uwella-Ratnapura, 11.5km NW of Balangoda; Ratnapura District, Sabaragamuwa Province; N6.6968, E80.6059; 16-vii-2012; to be deposited at National Museum of Natural History, Colombo, Sri Lanka), Platysticta secreta sp. nov. (holotype ♂: Hasalaka; Kandy District, Central Province; N7.3535, E80.9509; 31-v-1975; deposited at National Museum of Natural History, Smithsonian Institution, Washington, USA) and P. serendibica sp. nov. (holotype ♂: Kanneliya; Galle District, Southern Province; N6.2291, E80.3834; 8 & 9-vi-1975; deposited at National Museum of Natural History, Smithsonian Institution, Washington, USA). Additionally, a determination key, figures showing morphological details and coloration in life, as well as distribution maps for all species are presented. Based on molecular analysis of 21 taxa, the phylogeny of Platystictinae is presented and discussed from the zoogeographical and paleogeographical point of view. Sri Lankan species, traditionally placed in the genera Platysticta Selys and Drepanosticta Laidlaw / Ceylonosticta Fraser, separated into distinct clades within the subfamily as presently defined, but the monophyletic nature of the Platystictinae and its Sri Lankan endemicity is confirmed. For the South Indian species, formerly known as Platysticta deccanensis, morphological and molecular analyses demonstrated that it does not belong to the Sri Lankan clade and a new genus Indosticta gen. nov. is erected to accommodate it.

High-bandwidth uni-traveling carrier waveguide photodetector on an InP-membrane-on-silicon platform.

A uni-traveling carrier photodetector (UTC-PD), heterogeneously integrated on silicon, is demonstrated. It is fabricated in an InP-based photonic membrane bonded on a silicon wafer, using a novel double-sided processing scheme. A very high 3 dB bandwidth of beyond 67 GHz is obtained, together with a responsivity of 0.7 A/W at 1.55 µm wavelength. In addition, open eye diagrams at 54 Gb/s are observed. These results promise high speed applications using a novel full-functionality photonic platform on silicon.

Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial.

BACKGROUND: Only human epidermal growth factor receptor (HER)2 status determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to benefit from T-DM1. PATIENTS AND METHODS: HER2-positive mBC patients with IHC3+ or FISH ≥ 2.2 scheduled for T-DM1 underwent a pretreatment HER2-positron emission tomography (PET)/computed tomography (CT) with (89)Zr-trastuzumab. [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT was performed at baseline and before T-DM1 cycle 2. Patients were grouped into four HER2-PET/CT patterns according to the proportion of FDG-avid tumor load showing relevant (89)Zr-trastuzumab uptake (>blood pool activity): patterns A and B were considered positive (>50% or all of the tumor load 'positive'); patterns C and D were considered negative (>50% or all of the tumor load 'negative'). Early FDG-PET/CT was defined as nonresponding when >50% of the tumor load showed no significant reduction of FDG uptake (<15%). Negative (NPV) and positive predictive values (PPV) of HER2-PET/CT, early FDG response and their combination were assessed to predict morphological response (RECIST 1.1) after three T-DM1 cycles and time-to-treatment failure (TTF). RESULTS: In the 56 patients analyzed, 29% had negative HER2-PET/CT while intrapatient heterogeneity (patterns B and C) was found in 46% of patients. Compared with RECIST1.1, respective NPV/PPV for HER2-PET/CT were 88%/72% and 83%/96% for early FDG-PET/CT. Combining HER2-PET/CT and FDG-PET/CT accurately predicted morphological response (PPV and NPV: 100%) and discriminated patients with a median TTF of only 2.8 months [n = 12, 95% confidence interval (CI) 1.4-7.6] from those with a TTF of 15 months (n = 25, 95% CI 9.7-not calculable). CONCLUSIONS: Pretreatment imaging of HER2 targeting, combined with early metabolic response assessment holds great promise for improving the understanding of tumor heterogeneity in mBC and for selecting patients who will/will not benefit from T-DM1. CLINICALTRIALSGOV IDENTIFIER: NCT01565200.