Cubic-wavelength mode volume photonic crystal nanobeam cavities in a monolithic CMOS platform.

We report on the design, fabrication, and experimental characterization of photonic crystal (PhC) nanobeam cavities with the smallest footprint, largest intrinsic quality factor, and smallest mode volume to be demonstrated to date in a monolithic CMOS platform. Two types of cavities were designed, with opposite spatial mode symmetries. The opposite mode symmetry, combined with evanescent coupling, allows the nanobeam cavities to be used in reflectionless topologies, desirable in complex photonic integrated circuits (PICs). The devices were implemented and fabricated in a 45 nm monolithic electronics-photonics CMOS platform optimized for silicon photonics (GlobalFoundries 45CLO) and do not require any post-processing. Quality factors exceeding 100 000 were measured for both devices, the highest, to the best of our knowledge, among fully cladded PhC nanobeam cavities in any silicon-on-insulator (SOI) platform. Additionally, the ability of the cavities to confine light into small mode volumes, of the order of (λ/n)3, was confirmed experimentally using near-field scanning optical microscopy (NSOM). These types of cavities are an important step toward realizing ultra-low energy active devices required for the next generation of integrated optical links beyond the current microring resonator-based links and other CMOS PICs.

Polarization-insensitive 1D grating coupler based on a zero-birefringence subwavelength corelet waveguide.

Grating coupler devices provide efficient, foundry-compatible vertical fiber-to-chip coupling solutions in integrated photonic platforms. However, standard grating coupler designs are highly polarization sensitive, which hinders their adoption. We present a new, to the best of our knowledge, type of 1D polarization-insensitive grating coupler (PIGC) that is based on a zero-birefringence subwavelength "corelet" waveguide. We demonstrate a PIGC for coupling in the telecommunications O-band in a 45-nm-node monolithic silicon-on-insulator (SOI) CMOS electronic-photonic platform, with measured insertion losses of 6.7 and 6.1 dB to transverse electric and transverse magnetic polarizations, respectively, and a ±1-dB polarization dependent loss bandwidth of 73 nm.

Determinants of long-term opioid prescribing in an urban population: A cross-sectional study.

BACKGROUND: Opioid prescribing has more than doubled in the UK between 1998 and 2016. Potential adverse health implications include dependency, falls and increased health expenditure. AIM: To describe the predictors of long-term opioid prescribing (LTOP) (≥3 opioid prescriptions in a 90-day period). DESIGN AND SETTING: A retrospective cross-sectional study in 41 general practices in South London. METHOD: Multi-level multivariable logistic regression to investigate the determinants of LTOP. RESULTS: Out of 320 639 registered patients ≥18 years, 2679 (0.8%) were identified as having LTOP. Patients were most likely to have LTOP if they had ≥5 long-term conditions (LTCs) (adjusted odds ratio [AOR] 36.5, 95% confidence interval [CI] 30.4-43.8) or 2-4 LTCs (AOR 13.8, CI 11.9-16.1) in comparison to no LTCs, were ≥75 years compared to 18-24 years (AOR 12.31, CI 7.1-21.5), were smokers compared to nonsmokers (AOR 2.2, CI 2.0-2.5), were female rather than male (AOR 1.9, CI 1.7-2.0) and in the most deprived deprivation quintile (AOR 1.6, CI 1.4-1.8) compared to the least deprived. In a separate model examining individual LTCs, the strongest associations for LTOP were noted for sickle cell disease (SCD) (AOR 18.4, CI 12.8-26.4), osteoarthritis (AOR 3.0, CI 2.8-3.3), rheumatoid arthritis (AOR 2.8, CI 2.2-3.4), depression (AOR 2.6, CI 2.3-2.8) and multiple sclerosis (OR 2.5, CI 1.4-4.4). CONCLUSION: LTOP was significantly higher in those aged ≥75 years, with multimorbidity or specific LTCs: SCD, osteoarthritis, rheumatoid arthritis, depression and multiple sclerosis. These characteristics may enable the design of targeted interventions to reduce LTOP.

Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity.

Tyrosine kinase inhibitors (TKIs) are used to treat several cancers; however, a myriad of adverse cardiotoxic effects remain a primary concern. Although hypertension (HTN) is the most common adverse effect reported with TKI therapy, incidents of arrhythmias (eg, QT prolongation, atrial fibrillation) and heart failure are also prevalent. These complications warrant further research toward understanding the mechanisms of TKI-induced cardiotoxicity. Recent literature has given some insight into the intracellular signaling pathways that may mediate TKI-induced cardiac dysfunction. In this article, we discuss the cardiotoxic effects of TKIs on cardiomyocyte function, signaling, and possible treatments.

Prevalence of mental illness among parents of children receiving treatment within child and adolescent mental health services (CAMHS): a scoping review.

People affected by mental illness often come from families with patterns of mental illness that span across generations. Hence, child and adolescent mental health services (CAMHS) likely provide treatment to many children with parents who also experience mental illness. The aim of this scoping review was to: (1) identify the prevalence of mental illness among parents of children in CAMHS; (2) identify and appraise the methodologies that have been implemented to assess the prevalence of parental mental illness in CAMHS; (3) identify additional circumstances associated with families where both parent and child experience mental illness; and (4) present recommendations that have been made for CAMHS practice based on these findings. English language, peer-reviewed studies (2010-2018) that had investigated the mental health of parents in CAMHS were included in the review. Literature searching yielded 18 studies which were found to have utilised diverse methodologies to assess parental mental health. Overall, reported prevalence of parental mental illness ranged from 16 to 79%; however, a single study that was deemed to be comprehensive reported prevalence rates of 36% for mothers and 33% for fathers. Across studies, parent and child mental illness was found to be associated with additional adversities impacting family functioning and wellbeing. For children who receive treatment for mental illness, having a parent who also experiences mental illness is a frequent family circumstance that has implications for their prospects for recovery. Accordingly, the mental health of parents should be an important consideration within the mental health care CAMHS provide to children.

Is rapid scientific publication also high quality? Bibliometric analysis of highly disseminated COVID-19 research papers.

The impact of COVID-19 has underlined the need for reliable information to guide clinical practice and policy. This urgency has to be balanced against disruption to journal handling capacity and the continued need to ensure scientific rigour. We examined the reporting quality of highly disseminated COVID-19 research papers using a bibliometric analysis examining reporting quality and risk of bias (RoB) amongst 250 top scoring Altmetric Attention Score (AAS) COVID-19 research papers between January and April 2020. Method-specific RoB tools were used to assess quality. After exclusions, 84 studies from 44 journals were included. Forty-three (51%) were case series/studies, and only one was an randomized controlled trial. Most authors were from institutions based in China (n = 44, 52%). The median AAS and impact factor was 2015 (interquartile range [IQR] 1,105-4,051.5) and 12.8 (IQR 5-44.2) respectively. Nine studies (11%) utilized a formal reporting framework, 62 (74%) included a funding statement, and 41 (49%) were at high RoB. This review of the most widely disseminated COVID-19 studies highlights a preponderance of low-quality case series with few research papers adhering to good standards of reporting. It emphasizes the need for cautious interpretation of research and the increasingly vital responsibility that journals have in ensuring high-quality publications.

Extraordinary optical transmission in nano-bridged plasmonic arrays mimicking a stable weakly-connected percolation threshold.

Ultrasensitive sensors of various physical properties can be based on percolation systems, e.g., insulating media filled with nearly touching conducting particles. Such a system at its percolation threshold featuring the critical particle concentration, changes drastically its response (electrical conduction, light transmission, etc.) when subjected to an external stimulus. Due to the critical nature of this threshold, a given state at the threshold is typically very unstable. However, stability can be restored without significantly sacrificing the structure sensitivity by forming weak connections between the conducting particles. In this work, we employed nano-bridged nanosphere lithography to produce such a weakly connected percolation system. It consists of two coupled quasi-Babinet complementary arrays, one with weakly connected, and the other with disconnected metallic islands. We demonstrate via experiment and simulation that the physics of this plasmonic system is non-trivial, and leads to the extraordinary optical transmission at narrowly defined peaks sensitive to system parameters, with surface plasmons mediating this process. Thus, our system is a potential candidate for percolation effect based sensor applications. Promising detection schemes could be based on these effects.

Optical confinement in the nanocoax: coupling to the fundamental TEM-like mode.

The nanoscale coaxial cable (nanocoax) has demonstrated optical confinement in the visible and the near infrared. We report on a novel nanofabrication process which yields optically addressable, sub-µm diameter, and high aspect ratio metal-insulator-metal nanocoaxes made by atomic layer deposition of Pt and Al2O3. We observe sub-diffraction-limited optical transmission via the fundamental, TEM-like mode by excitation with a radially polarized optical vortex beam. Our experimental results are based on interrogation with a polarimetric imager. Finite element method numerical simulations support these results, and their uniaxial symmetry was exploited to model taper geometries with both an electrically large volume, (15λ)3, and a nanoscopic exit aperture, (λ/200)2.

Facile fabrication and formation mechanism of aluminum nanowire arrays.

Anodized alumina membranes (AAMs) have proven effective at making vertically-oriented and well-ordered metal nanowire arrays, which are useful in plasmonics and electrochemistry. Here, we produced Al nanowires via directed AAM pore nucleation: a patterned oxide mask on a flat Al surface directed where pores did and did not form, the pores acting to oxidize Al around the sites without pores. This left Al nanowires embedded in the AAM, and produced freestanding Al nanowires after etching the AAM. The nanowire tops had two distinct contours, smooth bowls and flat rough surfaces-suggesting that nanowires with bowl tops result from slow pore development relative to pattern-nucleated pores, not pore blockage as prior literature suggests. The observed low porosity of ∼2%, as opposed to the more typical 10%, suggests pore nucleation in the electrolyte employed may need greater local variations in electric field or pH, possibly explaining the electrolyte's peculiar ability to make Al nanowires. Finally, a soft nano-imprint lithography process was developed here to pattern the mask without damaging the stamp, avoiding a stamp degradation problem in previous work that utilized hard nano-imprint lithography.

Nano-bridged nanosphere lithography.

We develop nano-bridged nanosphere lithography (NB-NSL), a modification to the widely used conventional nanosphere lithography (NSL). Nano-bridges between polystyrene (PS) spheres of a pristine NSL template are controllably formed in a two-step process: (i) spin-coating of a dilute styrene solution on top of the template, followed by (ii) oxygen plasma etching of the template. We show that the nanobridge dimensions can be precisely tuned by controlling the pre-processing conditions and the plasma etching time. The resulting lithography templates feature control over the shape and size of the apertures, which determine the morphology of the final nano-island arrays after material deposition and template removal. The unique advantage of NB-NSL is that PS particle templates based on a single PS particle diameter can be utilized for the fabrication of a variation of nano-island shapes and sizes, whereas conventional NSL yields only bowtie-shaped nano-islands, with their size being predetermined by the PS particle diameter of the template.

Predictors of Locoregional Recurrence After Failure to Achieve Pathologic Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

BACKGROUND: This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). METHODS: This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. RESULTS: A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64-9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35-8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). CONCLUSIONS: In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.

Treatment response as predictor for brain metastasis in triple negative breast cancer: A score-based model.

BACKGROUND: Triple negative breast cancer (TNBC) has worse prognosis than other subtypes of breast cancer, and many patients develop brain metastasis (BM). We developed a simple predictive model to stratify the risk of BM in TNBC patients receiving neo-adjuvant chemotherapy (NAC), surgery, and radiation therapy (RT). METHODS: Patients with TNBC who received NAC, surgery, and RT were included. Cox proportional hazards method was used to evaluate factors associated with BM. Significant factors predictive for BM on multivariate analysis (MVA) were used to develop a risk score. Patients were divided into three risk groups: low, intermediate, and high. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of the risk group in predicting BM. This predictive model was externally validated. RESULTS: A total of 160 patients were included. The median follow-up was 47.4 months. The median age at diagnosis was 49.9 years. The 2-year freedom from BM was 90.5%. Persistent lymph node positivity, HR 8.75 (1.76-43.52, P = 0.01), and lack of downstaging, HR 3.46 (1.03-11.62, P = 0.04), were significant predictors for BM. The 2-year rate of BM was 0%, 10.7%, and 30.3% (P < 0.001) in patients belonging to low-, intermediate-, and high-risk groups, respectively. Area under the ROC curve was 0.81 (P < 0.001). This model was externally validated (C-index = 0.79). CONCLUSIONS: Lack of downstaging and persistent lymph node positivity after NAC are associated with development of BM in TNBC. This model can be used by the clinicians to stratify patients into the three risk groups to identify those at increased risk of developing BM and potentially impact surveillance strategies.

Emerging Perspectives on mTOR Inhibitor-Associated Pneumonitis in Breast Cancer.

Substantial improvements in the early detection and treatment of breast cancer have led to improvements in survival, but breast cancer remains a significant cause of morbidity and mortality in women. In 2012, the mammalian target of rapamycin (mTOR) inhibitor everolimus was approved by the U.S. Food and Drug Administration for the treatment of advanced breast cancer in patients resistant to endocrine therapy. Although everolimus is generally well tolerated, mTOR inhibitor-associated pneumonitis is one of the most common adverse drug events leading to treatment discontinuation. To date, the underlying pathophysiology of this toxicity is unclear, and this uncertainty may hinder the optimization of management strategies. However, experiences from breast cancer and renal cell carcinoma clinical trials indicate that mTOR inhibitor-associated pneumonitis can be effectively managed by early detection, accurate diagnosis, and prompt intervention that generally involves everolimus dose reductions, interruptions, or discontinuation. Management can be achieved by a multidisciplinary approach that involves the collaborative efforts of nurses, oncologists, radiologists, infectious disease specialists, pulmonologists, clinical pharmacists, and pathologists. Comprehensive education must be provided to all health care professionals involved in managing patients receiving everolimus therapy. Although general recommendations on the management of mTOR inhibitor-associated pneumonitis have been published, there is a lack of consensus on the optimal management of this potentially serious complication. This article provides an overview of mTOR inhibitor-associated pneumonitis, with a focus on the detection, accurate diagnosis, and optimal management of this class-related complication of mTOR inhibitor therapy. IMPLICATIONS FOR PRACTICE: This article summarizes the pathogenesis, clinical presentation, incidence, detection, and optimal management of everolimus-related noninfectious pneumonitis in breast cancer. In particular, this article provides a detailed overview of the important aspects of the detection, accurate diagnosis, and appropriate management of mammalian target of rapamycin inhibitor-associated pneumonitis. In addition, this article emphasizes that effective management of this adverse drug event in patients with breast cancer will require a multidisciplinary approach and collaboration among various health care professionals.

Evaluation of [89Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer.

PURPOSE: To evaluate whether tumor uptake of [89Zr]trastuzumab can distinguish HER2-positive from HER2-negative breast cancer. METHODS: Women with HER2-positive (n = 34) and HER2-negative (n = 16) breast cancer underwent PET/CT 5 ± 2 days following [89Zr]trastuzumab administration. HER2 status was determined based on immunohistochemistry and/or fluorescence in situ hybridization of primary or metastatic/recurrent tumor. Tumor [89Zr]trastuzumab uptake was assessed qualitatively and semiquantitatively as maximum standardized uptake value (SUVmax), and correlated with HER2 status. Additionally, intrapatient heterogeneity of [89Zr]trastuzumab uptake was evaluated. RESULTS: On a per-patient basis, [89Zr]trastuzumab-PET/CT was positive in 30/34 (88.2%) HER2-positive and negative in 15/16 (93.7%) HER2-negative patients. Considering all lesions, the SUVmax was not significantly different in patients with HER2-positive versus HER2-negative disease (p = 0.06). The same was true of when only hepatic lesions were evaluated (p = 0.42). However, after excluding hepatic lesions, tumor SUVmax was significantly higher in HER2-positive compared to HER2-negative patients (p = 0.003). A cutoff SUVmax of 3.2, determined by ROC analysis, demonstrated positive-predictive value of 83.3% (95% CI 65.3%, 94.4%), sensitivity of 75.8% (57.7%, 88.9%), negative-predictive value of 50% (24.7%, 75.3%), and specificity of 61.5% (95% 31.6%, 86.1%) for differentiating HER2-positive from HER2-negative lesions. There was intrapatient heterogeneity of [89Zr]trastuzumab uptake in 20% of patients with multiple lesions. CONCLUSIONS: [89Zr]trastuzumab has the potential to characterize the HER2 status of the complete tumor burden in patients with breast cancer, thus obviating repeat or multiple tissue sampling to assess intrapatient heterogeneity of HER2 status.

Impact of Neoadjuvant and Adjuvant Chemotherapy on Immediate Tissue Expander Breast Reconstruction.

BACKGROUND: Delayed wound healing or infection leads to premature tissue expander (TE) explantation after immediate postmastectomy breast reconstruction. A large study with sufficient duration of follow-up focusing on the impact of chemotherapy (CT) on premature TE removal after immediate breast reconstruction is lacking. METHODS: A retrospective review of patients undergoing immediate TE reconstruction was conducted. Multivariate analyses identified factors contributing to premature removal of TEs including neoadjuvant and adjuvant CT, specific chemotherapeutic regimens, and other factors like cancer stage, body mass index, smoking, radiation, and age. Kaplan-Meier curves were plotted to study the timing of premature TE removal. RESULTS: Of 899 patients with TEs, 256 received no, 295 neoadjuvant, and 348 adjuvant CT. Premature removal occurred more frequently in the neoadjuvant (17.3 %) and adjuvant (19.9 %) cohorts than the no-CT (12.5 %) cohort (p = 0.056). Premature TE removal occurred earlier (p = 0.005) in patients who received no CT than those with adjuvant CT. Radiation in patients receiving neoadjuvant CT prolonged the mean time to premature removal (p = 0.003). In the absence of radiation, premature removal occurred significantly sooner with neoadjuvant than adjuvant CT (p = 0.035). DISCUSSION: Premature removal of a TE occurs more commonly in patients treated with neoadjuvant or adjuvant CT and is most commonly observed 2-3 months after placement-well after the follow-up period recorded by the American College of Surgeons National Surgery Quality Improvement Program (NSQIP) database. These findings can be used to aid preoperative counseling and guide the timing of follow-up for these patients.

Impact of a behavioral weight loss intervention on comorbidities in overweight and obese breast cancer survivors.

PURPOSE: Comorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss. METHODS: ENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses. RESULTS: At 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p < 0.001); however, by 24 months, there was no longer a significant difference. No difference was observed in each of the four conditions for which non-cancer medications were prescribed, hospital visits, or emergency visits at either 12 or 24 months. CONCLUSIONS: These results support a short-term benefit of modest weight loss on the likelihood of comorbid conditions; however, recidivism and weight regain likely explain no benefit at 1-year postintervention follow-up.

Aluminum Nanowire Arrays via Directed Assembly.

Freestanding and vertically-oriented metal nanowire arrays have potential utility in a number of applications, but presently lack a route to fabrication. Template-based techniques, such as electrodeposition into lithographically defined nanopore arrays, have produced well-ordered nanowire arrays with a maximum pitch of about 2 µm; such nanowires, however, tend to cluster due to local attractive forces. Here, we modify this template fabrication method to produce well-ordered, vertically-oriented, freestanding Al nanowire arrays, etched from an underlying Al substrate, with highly tunable pitch. In addition, optical measurements demonstrated that the nanowires support the propagation of surface plasmon polaritons.

Health Care, Business, and Ethics: The Goods We Hold in Common.

The common good is one of those terms that most of us think we understand until we start talking about it. Our conversations too often become platitudinous and moralistic, feeling more and more abstract and vague. As one health care executive said to me, "How would I know if the common good bit me?"

Effect of weight loss on bone health in overweight/obese postmenopausal breast cancer survivors.

Current guidelines recommend weight loss in obese cancer survivors. Weight loss, however, has adverse effects on bone health in obese individuals without cancer but this has not been evaluated in breast cancer survivors. We investigated the associations of intentional weight loss with bone mineral density (BMD) and bone turn-over markers in overweight/obese postmenopausal breast cancer survivors. Participants were overweight/obese breast cancer survivors (N = 81) with stage I, II or IIIA disease enrolled in the St. Louis site of a multi-site Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) study; a randomized-controlled clinical trial designed to achieve a sustained ≥7 % loss in body weight at 2 years. Weight loss was achieved through dietary modification with the addition of physical activity. Generalized estimating equations were used to assess differences in mean values between follow-up and baseline. Mean weight decreased by 3 and 2.3 % between baseline and 6-month follow-up, and 12-month follow-up, respectively. There were decreases in osteocalcin (10.6 %, p value < 0.001), PINP (14.5 %, p value < 0.001), NTx (19.2 % p value < 0.001), and RANK (48.5 %, p value < 0.001), but not BALP and CTX-1 levels between baseline and 12-month follow-up. No significant changes occurred in mean T-scores, pelvis and lumbar spine BMD between baseline and 12-month follow-up. A 2.3 % weight loss over 12 months among overweight/obese women with early-stage breast cancer does not appear to have deleterious effect on bone health, and might even have beneficial effect. These findings warrant confirmation, particularly among breast cancer survivors with a larger magnitude of weight loss.