Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic,multicenter cross-sectional cohort study

Background

The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities.

Methods

Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age–sex–ethnicity-matched controls. Additionally, we computed individual facial asymmetry.

Findings

A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p < .001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p = .002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p = .080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤ .001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p = .046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p = .009) and Paris-method (p = .007).

Interpretation

When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians’ bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options.     

A Proactive Approach to High Risk Delirium Patients Undergoing Total Joint Arthroplasty

Background

Delirium is a common complication among elderly patients undergoing total joint arthroplasty (TJA). Its incidence has been reported from 4% to 53%. The Centers for Medicare and Medicaid Services consider delirium following TJA a “never-event.” The purpose of this study is to evaluate a simple perioperative protocol used to identify delirium risk patients and prevent its incidence following TJA.

Ab initio study of hot electrons in GaAs

Hot carrier dynamics critically impacts the performance of electronic, optoelectronic, photovoltaic, and plasmonic devices. Hot carriers lose energy over nanometer lengths and picosecond timescales and thus are challenging to study experimentally, whereas calculations of hot carrier dynamics are cumbersome and dominated by empirical approaches. In this work, we present ab initio calculations of hot electrons in gallium arsenide (GaAs) using density functional theory and many-body perturbation theory. Our computed electron–phonon relaxation times at the onset of the Γ, L, and X valleys are in excellent agreement with ultrafast optical experiments and show that the ultrafast (tens of femtoseconds) hot electron decay times observed experimentally arise from electron–phonon scattering. This result is an important advance to resolve a controversy on hot electron cooling in GaAs. We further find that, contrary to common notions, all optical and acoustic modes contribute substantially to electron–phonon scattering, with a dominant contribution from transverse acoustic modes. This work provides definitive microscopic insight into hot electrons in GaAs and enables accurate ab initio computation of hot carriers in advanced materials.Hot carriers (HCs) generated by the absorption of light or injection at a contact are commonly found in many advanced technologies (1–9). In electronics, the operation of high-speed devices is controlled by HC dynamics, and HC injection is a key degradation mechanism in transistors (10, 11). In solar cells and plasmonics, recent work has focused on extracting the kinetic energy of HCs before cooling (7, 9), a process defined here as the energy loss of HCs, ultimately leading to thermal equilibrium with phonons. HC dynamics is also crucial to interpret time-resolved spectroscopy experiments used to study excited states in condensed matter (12). This situation has sparked a renewed interest in HCs in a broad range of materials of technological relevance.Experimental characterization of HCs is challenging because of the subpicosecond timescale associated with the electron–phonon (e-ph) and electron–electron (e-e) scattering processes regulating HC dynamics. For example, HCs can be studied using ultrafast spectroscopy, but microscopic interpretation of time-resolved spectra requires accurate theoretical models. However, modeling of HCs thus far has been dominated by empirical approaches, which do not provide atomistic details and use ad hoc parameters to fit experiments (13, 14). Notwithstanding the pioneering role of these early studies, the availability of accurate ab initio computational methods based on density functional theory (DFT) (15) and many-body perturbation theory (16) enables studies of HCs with superior accuracy, broad applicability, and no need for fitting parameters.Hot electrons in gallium arsenide (GaAs) are of particular interest because of the high electron mobility and multivalley character of the conduction band. Electrons excited at energies greater than ∼0.5 eV above the conduction band minimum (CBM) can transfer from the Γ to the L and X valleys, with energy minima at ∼0.25 and ∼0.45 eV above the CBM, respectively (17). Such intervalley scattering processes play a crucial role in hot electron cooling and transport at high electric fields.Ample experimental data exist on hot electron transport and cooling in GaAs (12, 18–21). The interpretation of these experiments relies on Monte Carlo simulations using multiple parameters fit to experimental results. For example, Fischetti and Laux (13) used two empirical deformation potentials to model electron scattering induced by optical and acoustic phonons. Additionally, Fischetti and Laux (13) used simplified band structure and phonon dispersions. We note that, because multiple parameter sets can fit experimental results, the HC scattering rates due to different physical processes obtained empirically are not uniquely determined (13, 14).Although heuristic approaches can provide some insight into HC dynamics of well-characterized materials (e.g., GaAs), there is a lack of generally applicable, predictive, and parameter-free approaches to study HCs.Here, we carry out ab initio calculations of hot electrons in GaAs with energies up to 5 eV above the CBM. Our ability to use extremely fine grids in the Brillouin zone (BZ) allows us to resolve hot electron scattering in the conduction band with unprecedented accuracy. We focus here on three main findings. First, our overall computed e-ph scattering rates are in excellent agreement with those in previous semiempirical calculations in ref. 13 that combine multiple empirical parameters. The advantage of our approach is the ability to compute the electronic band and momentum dependence of the e-ph scattering rates without fitting parameters. Second, we show that both optical and acoustic modes contribute substantially to e-ph scattering, with a dominant scattering from transverse acoustic (TA) modes. This result challenges the tenet that HCs lose energy mainly through longitudinal optical (LO) phonon emission. Third, our calculations provide valuable means for quantitative interpretation of experiments of hot electron cooling in GaAs. In particular, the ultrafast (∼50 fs) e-ph relaxation times that we compute at the onset of the X valley are in excellent agreement with the fastest decay time observed in ultrafast optical experiments (18, 19, 21). This signal was attributed by some (18) to e-e scattering and by others (21) to e-ph scattering. The excellent agreement with time decay signals in time-resolved experiments shows the dominant role of e-ph scattering for hot electron cooling at low carrier density.Our approach combines electronic band structures computed ab initio using the GW (where G is the Green function, W is the screened Coulomb potential, and GW is the diagram employed for the electron exchange-correlation interactions) method (16) with phonon dispersions from density functional perturbation theory (DFPT) (22), and it is entirely free of empirical parameters. We compute the e-ph matrix elements using a Wannier function formalism (23) on very fine BZ grids and are able to resolve e-ph scattering for the different conduction band valleys. The e-e rates for hot electrons—also known as impact ionization (II) rates—are computed using the GW method (16, 24), and thus include dynamical screening effects. Additional details of our calculations are discussed in Methods.     

A Qualitative Exploration of the Views of Policymakers and Policy Advisors on the Impact of Mental Health Stigma on the Development and Implementation of Mental Health Policy in Singapore

Few studies have examined the views of policy makers regarding the impact of mental health stigma on the development and implementation of mental health policies. This study aimed to address this knowledge gap by exploring policymakers’ and policy advisors’ perspectives regarding the impact of mental health stigma on the development and implementation of mental health programmes, strategies, and services in Singapore. In all 13 participants were recruited for the study comprising practicing policymakers, senior staff of organisations involved in implementing the various mental health programmes, and policy advisors. Data was collected through semi-structured interviews, which were transcribed verbatim and analysed using reflexive thematic analysis. Data analysis revealed three superordinate themes related to challenges experienced by the policymakers/advisors when dealing with mental health policy and implementation of programmes. These themes included stigma as a barrier to mental health treatment, community-level barriers to mental health recovery, and mental health being a neglected need. Policymakers/advisors demonstrated an in-depth and nuanced understanding of the barriers (consequent to stigma) to mental healthcare delivery and access. Policymakers/advisors were able to associate the themes related to the stigma towards mental illness with help-seeking barriers based on personal experiences, knowledge, and insight gained through the implementation of mental health programmes and initiatives.

     

Surgical training for anatomical endoscopic enucleation of the prostate

Anatomical endoscopic enucleation of the prostate has been proposed as a potentially superior benign prostatic hyperplasia surgery than conventional transurethral resection of prostate. However, the learning curve of the procedure is steep, hence limiting its generalisability worldwide. In order to overcome the learning curve, a proper surgical training is extremely important. This review article discussed about various aspects of surgical training in anatomical endoscopic enucleation of the prostate. In summary, no matter what surgical technique or energy modality you use, the principle of anatomical enucleation should be followed. When one starts to perform prostate enucleation, a 50 to 80 g prostate appears to be the ‘best case’ to begin with. Mentorship is extremely important to shorten the learning curve and to prevent drastic complications from the procedure. A proficiency-based progression training programme with the use of simulation and training models should be the best way to teach and learn about prostate enucleation. Enucleation ratio efficacy is the preferred measure for assessing skill level and learning curve of prostate enucleation. Morcellation efficiency is commonly used to assess morcellation performance, but the importance of safety rather than efficiency must be emphasised.     

Window of opportunity treatment in breast cancer

Window of opportunity therapies, which involve short‐term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone‐receptor positive breast cancer, a 2‐week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision‐making regarding treatment options. Changes in short‐term biomarker endpoints such as cell proliferation measured by Ki‐67 can act as surrogate markers of long‐term outcomes. Paired tissues obtained pre‐ and post‐investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.     

Nanoparticle Albumin-bound Paclitaxel Plus Carboplatin Induction Followed by Nanoparticle Albumin-bound Paclitaxel Maintenance in Squamous Non–Small-cell Lung Cancer (ABOUND.sqm): A Phase III Randomized Clinical Trial

BackgroundWe evaluated maintenance nanoparticle albumin-bound (nab) paclitaxel in the treatment of advanced squamous non–small-cell lung cancer.Patients and MethodsPatients with treatment-naive squamous non–small-cell lung cancer received four 21-day cycles of nab-paclitaxel 100 mg/m² on days 1, 8, 15 plus carboplatin area under the curve 6 on day 1 as induction therapy. Patients without disease progression after induction were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m² (days 1 and 8 every 21 days) plus best supportive care (BSC) or BSC alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety and overall survival (OS).ResultsOverall, 420 patients had received induction therapy; 202 (nab-paclitaxel plus BSC, 136; BSC, 66) had received maintenance therapy. Enrollment was discontinued after a preplanned interim futility analysis (patients could remain in the study at the investigator’s discretion). The median PFS was 3.12 months for nab-paclitaxel plus BSC and 2.60 months for BSC; the difference was not statistically significant (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61-1.19; P = .36). The median OS (median follow-up, 24.2 months) was 17.18 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.70; 95% CI, 0.48-1.02; nominal P = .07). An updated analysis (median follow-up, 28.4 months) revealed a median OS of 17.61 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.68; 95% CI, 0.47-0.98; nominal P = .037). The most frequent grade 3 and 4 treatment-emergent adverse events for the entire study were neutropenia (53.1% [nab-paclitaxel plus BSC] vs. 50.0% [BSC]) and anemia (33.1% [nab-paclitaxel plus BSC] vs. 32.3% [BSC]). Only peripheral neuropathy had occurred in ≥ 5% of patients during maintenance therapy (13.1%; nab-paclitaxel plus BSC).ConclusionsThe results of the ABOUND.sqm did not meet the primary endpoint of PFS. An updated OS analysis revealed a trend favoring nab-paclitaxel plus BSC.