Effect of Patterned Slip on Micro and Nanofluidic Flows

We consider the flow of a Newtonian fluid in a nano or microchannel with walls that have patterned variations in slip length. We formulate a set of equations to describe the effects on an incompressible Newtonian flow of small variations in slip, and solve these equations for slow flows. We test these equations using molecular dynamics simulations of flow between two walls which have patterned variations in wettability. Good qualitative agreement and a reasonable degree of quantitative agreement is found between the theory and the molecular dynamics simulations. The results of both analyses show that patterned wettability can be used to induce complex variations in flow. Finally we discuss the implications of our results for the design of microfluidic mixers using slip.Comment: 13 pages, 12 figures, final version for publicatio

Precise wavefunction engineering with magnetic resonance

Controlling quantum fluids at their fundamental length scale will yield superlative quantum simulators, precision sensors, and spintronic devices. This scale is typically below the optical diffraction limit, precluding precise wavefunction engineering using optical potentials alone. We present a protocol to rapidly control the phase and density of a quantum fluid down to the healing length scale using strong time-dependent coupling between internal states of the fluid in a magnetic field gradient. We demonstrate this protocol by simulating the creation of a single stationary soliton and double soliton states in a Bose-Einstein condensate with control over the individual soliton positions and trajectories, using experimentally feasible parameters. Such states are yet to be realized experimentally, and are a path towards engineering soliton gases and exotic topological excitations.Comment: 8+ pages, 3 figures; revised parameters and added section about optimisation of adiabatic, finite-duration pulses and analytic resolution limi

Precise wave-function engineering with magnetic resonance

Controlling quantum fluids at their fundamental length scale will yield superlative quantum simulators, precision sensors, and spintronic devices. This scale is typically below the optical diffraction limit, precluding precise wave-function engineering using optical potentials alone. We present a protocol to rapidly control the phase and density of a quantum fluid down to the healing length scale using strong time-dependent coupling between internal states of the fluid in a magnetic field gradient. We demonstrate this protocol by simulating the creation of a single stationary soliton and double soliton states in a Bose-Einstein condensate with control over the individual soliton positions and trajectories, using experimentally feasible parameters. Such states are yet to be realized experimentally, and are a path towards engineering soliton gases and exotic topological excitations.This work was supported by the Australian Research Council (ARC) Centre of Excellence for Engineered Quantum Systems (Project No. CE110001013), the Australian Postgraduate Award Scheme, and ARC Grants No. DP1094399, No. DP130101613, and No. FT120100291

Hypoxia and reduced salinity exacerbate the effects of oil exposure on sheepshead minnow (Cyprinodon variegatus) reproduction

Environmental Biolog

Neoadjuvant nivolumab and nivolumab plus ipilimumab induce (near-) complete responses in patients with head and neck squamous cell carcinoma:The IMCISION trial

BackgroundNivolumab (NIVO) alone or with ipilimumab (COMBO) immune checkpoint blockade (ICB) prior to curative surgery has shown promising results in multiple tumor types. We completed a phase Ib/II study with neoadjuvant NIVO or COMBO in resectable head and neck squamous cell carcinoma (HNSCC) and show safety, efficacy and correlative biomarker results.Methods32 stage II-IVB HNSCC patients indicated for curative (salvage) surgery were treated with NIVO (240mg, weeks 1&3, N=6) or NIVO (240mg, weeks 1&3) + IPI (1mg/kg, week 1, N=26) prior to surgery in week 5. Imaging was performed at baseline and week 4. AEs were reported in terms of CTCAE. Pathological response (pR) was defined as % change in viable tumor cells from baseline to on-treatment; ≥90% pR was considered (near-) complete response (pCR). WES and RNAseq were performed on paired tumor biopsies.Results32 (31 HPV-negative) patients started treatment (stage II n=3, III n=8, IVA-B n=11, recurrent disease n=10). 6 patients included with recurrent disease had had previous (C)RT. 1 patient discontinued ICB after one course due to patient’s preference. Surgery was not postponed in any patient. 3/32 patients did not undergo surgery: 1 due to unresectable PD and 2 due to reasons unrelated to ICB or disease. Grade 3-4 irAEs in 11/32 patients were well manageable. (Near-)pCR in the primary tumor was seen in 9/29 evaluable patients (31%). Another 31% of patients had 20-89% pR. At 14 months median FU, RFS for patients with (near-)pCR was 100%, significantly better than patients with <90% pR (p=<0.05). Metabolic response assessment with FDG-PET (week 4) was able to identify (near-)pCRs. A baseline AID/APOBEC-associated tumor mutational profile was correlated with (near)pCR (p=<0.05). Finally, (near)pCR tumors were characterized by a decrease in hypoxia gene expression after ICB.ConclusionsNeoadjuvant ICB was feasible in HNSCC and induced (near)pCR in 31% of evaluable patients at time of surgery, which was accompanied by 100% RFS. Baseline AID/APOBEC-related mutations, on-treatment FDG-PET and resolution of hypoxia need future validation to discover their potential role as biomarkers for (near)pCR after ICB in HNSCC

The tubarial salivary glands:A potential new organ at risk for radiotherapy

Introduction: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. Materials and methods: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. Results: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated posttreatment xerostomia and dysphagia >= grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p =.007; 0.016/gy, 95%CI 0.001-0.031, p =.036). Follow-up at 24 months had similar results. Conclusion: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life. (C) 2020 The Authors. Published by Elsevier B.V

Revisiting Brain Atrophy and Its Relationship to Disability in Multiple Sclerosis

Brain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment.Based on MRI scans of 60 MS cases and 37 healthy volunteers, we measured the volumes of white matter (WM) lesions, cortical gray matter (GM), cerebral WM, caudate nucleus, putamen, thalamus, ventricles, and brainstem using a validated and completely automated segmentation method. We correlated these volumes with the Expanded Disability Status Scale (EDSS), MS Severity Scale (MSSS), MS Functional Composite (MSFC), and quantitative measures of ankle strength and toe sensation. Normalized volumes of both cortical and subcortical GM structures were abnormally low in the MS group, whereas no abnormality was found in the volume of the cerebral WM. High physical disability was associated with low cerebral WM, thalamus, and brainstem volumes (partial correlation coefficients ~0.3-0.4) but not with low cortical GM volume. Thalamus volumes were inversely correlated with lesion load (r = -0.36, p<0.005).The GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC