This paper employed a one-dimensional large-deformation model in consideration of the coupling of mechanical consolidation and solute transport, to study the transport of contaminants in a ...largely-deformed aquitard. An analytical solution has been derived to describe the drawdown variation in a largely-deformed aquitard which is subjected to abrupt hydraulic head decline in adjacent confined aquifers. The pore water flux and void ratio variation were obtained on the basis of the analytical solution. The equation for transient contaminant flux was solved by the finite difference method. A hypothetical case study was done to explore the effect of consolidation on the contaminant transport in a largely-deformed aquitard. The transit time of contaminant transport in the aquitard is mainly determined by the hydraulic conductivity, thickness, partitioning coefficient, void ratio and effective diffusion coefficients of aquitard, as well as the drawdown in the adjacent confined aquifer. The impact of delayed drainage on the contaminant transport in the largely-deformed aquitard is mainly controlled by two factors: the transient water flow and the decrease of aquitard thickness, in the process of aquitard consolidation. The former increases the breakthrough time of contaminant transport in the aquitard, and the latter gives rise to an opposite case with its effect decreasing with increasing contaminant partitioning coefficient for soil particles sorption. A larger deformation, which may be induced by a larger thickness, higher specific storativity of aquitard or a larger drawdown of the adjacent confined aquifer, and a lower hydraulic conductivity of aquitard cause a more significant impact of delayed drainage on the contaminant transport in an aquitard.
•An analytical solution was proposed to depict the drawdown change in an aquitard.•Factors determining the transit time of contaminant transport in aquitards are given.•Two governing factors of delayed drainage impact on contaminant transport are given.
The mechanical response and damage accumulation of carbon-fiber-reinforced composite laminates subjected to repeated low-velocity impacts were experimentally investigated. The repeated impact tests ...were conducted on 90
/-45
/0
/45
quasi-isotropic and 90
/0
cross-ply composite laminates under 16.8 J impact energy, respectively. For each impact, impact responses such as force-time, force-displacement and energy-time curves were recorded. The trends of peak force, maximum central displacement, energy absorption rate and bending stiffness with the increasing impact number were summarized, and the maximum number of repeated impacts corresponded to the occurrence of penetration events. The results showed that the delamination initiation, fiber breakage and penetration were the three typical characteristics describing the damage evolution of the repeated impacts. The damage accumulation of both the laminates was characterized by employing appropriate damage indices. By contrast, the quasi-isotropic laminates had higher impact resistance and damage tolerance, and their damage accumulation was relatively slower.
Minimal residual disease (MRD) is highly prognostic in pediatric B-precursor acute lymphoblastic leukemia (B-ALL). In Children's Oncology Group high-risk B-ALL study AALL0232, we investigated MRD in ...subjects randomized in a 2 × 2 factorial design to receive either high-dose methotrexate (HD-MTX) or Capizzi methotrexate (C-MTX) during interim maintenance (IM) or prednisone or dexamethasone during induction. Subjects with end-induction MRD ≥0.1% or those with morphologic slow early response were nonrandomly assigned to receive a second IM and delayed intensification phase. MRD was measured by 6-color flow cytometry in 1 of 2 reference labs, with excellent agreement between the two. Subjects with end-induction MRD <0.01% had a 5-year event-free survival (EFS) of 87% ± 1% vs 74% ± 4% for those with MRD 0.01% to 0.1%; increasing MRD amounts was associated with progressively worse outcome. Subjects converting from MRD positive to negative by end consolidation had a relatively favorable 79% ± 5% 5-year disease-free survival vs 39% ± 7% for those with MRD ≥0.01%. Although HD-MTX was superior to C-MTX, MRD retained prognostic significance in both groups (86% ± 2% vs 58% ± 4% for MRD-negative vs positive C-MTX subjects; 88% ± 2% vs 68% ± 4% for HD-MTX subjects). Intensified therapy given to subjects with MRD >0.1% did not improve either 5-year EFS or overall survival (OS). However, these subjects showed an early relapse rate similar to that seen in MRD-negative ones, with EFS/OS curves for patients with 0.1% to 1% MRD crossing those with 0.01% to 0.1% MRD at 3 and 4 years, thus suggesting that the intensified therapy altered the disease course of MRD-positive subjects. Additional interventions targeted at the MRD-positive group may further improve outcome. This trial was registered at www.clinicaltrials.gov as #NCT00075725.
•MRD measured by flow cytometry is prognostic in childhood B-ALL even with more effective high-dose methotrexate therapy.•Intensive therapy in MRD-positive patients altered the timing of relapse but did not overcome the poor prognostic significance of MRD.
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined ...the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed patients with childhood B-lineage ALL with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of whom were excluded from additional analyses because of the presence of BCR-ABL1 (n = 46) or ETV6-RUNX1 (n = 11). Among the remaining 284 patients (20.4%), overexpression and rearrangement of CRLF2 (IGH-CRLF2 or P2RY8-CRLF2) were identified in 124 (43.7%), with concomitant genomic alterations activating the JAK-STAT pathway (JAK1, JAK2, IL7R) identified in 63 patients (50.8% of those with CRLF2 rearrangement). Among the remaining patients, using reverse transcriptase polymerase chain reaction or transcriptome sequencing, we identified targetable ABL-class fusions (ABL1, ABL2, CSF1R, and PDGFRB) in 14.1%, EPOR rearrangements or JAK2 fusions in 8.8%, alterations activating other JAK-STAT signaling genes (IL7R, SH2B3, JAK1) in 6.3% or other kinases (FLT3, NTRK3, LYN) in 4.6%, and mutations involving the Ras pathway (KRAS, NRAS, NF1, PTPN11) in 6% of those with Ph-like ALL. We identified 8 new rearrangement partners for 4 kinase genes previously reported to be rearranged in Ph-like ALL. The current findings provide support for the precision-medicine testing and treatment approach for Ph-like ALL implemented in Children's Oncology Group ALL trials.
•Ph-like ALL is characterized by a diverse array of genetic alterations activating cytokine receptor and tyrosine kinase signaling.•Pediatric patients with Ph-like ALL can be identified in real time for effective treatment stratification.
Background/Objectives
Dementia‐related behavioral symptoms and functional dependence result in poor quality of life for persons with dementia and their caregivers. The goal was to determine whether a ...home‐based activity program (Tailored Activity Program; TAP‐VA) would reduce behavioral symptoms and functional dependence of veterans with dementia and caregiver burden.
Design
Single‐blind (interviewer), parallel, randomized, controlled trial (Clinicaltrials.gov: NCT01357564).
Setting
Veteran's homes.
Participants
Veterans with dementia and their family caregivers (N = 160 dyads).
Intervention
Dyads in TAP‐VA underwent 8 sessions with occupational therapists to customize activities to the interests and abilities of the veterans and educate their caregivers about dementia and use of customized activity. Caregivers assigned to attention control received up to 8 telephone‐based dementia education sessions with a research team member.
Measurements
Primary outcomes included number of behaviors and frequency of their occurrence multiplied by severity of occurrence; secondary outcomes were functional dependence, pain, emotional well‐being, caregiver burden (time spent caregiving, upset with behaviors) and affect at 4 (primary endpoint) and 8 months.
Results
Of 160 dyads (n = 76 TAP‐VA; n = 84 control), 111 completed 4‐month interviews (n = 51 TAP‐VA; n = 60 control), and 103 completed 8‐month interviews (n = 50 TAP‐VA; n = 53 control). At 4 months, compared to controls, the TAP‐VA group showed reductions in number (difference in mean change from baseline = −0.68, 95% CI = −1.23 to −0.13) and frequency by severity (−24.3, 95% CI = −45.6 to −3.1) of behavioral symptoms, number of activities needing assistance with (−0.80, 95% CI = −1.41 to −0.20), functional dependence level (4.09, 95% CI = 1.06, 7.13), and pain (−1.18, 95% CI = −2.10 to −0.26). Caregivers of veterans in TAP‐VA reported less behavior‐related distress. Benefits did not extend to 8 months.
Conclusion
TAP‐VA had positive immediate effects and no adverse events. Because TAP‐VA reduces behavioral symptoms, slows functional dependence, and alleviates pain and caregiver distress, it is a viable treatment option for families.
Low-velocity impact (LVI) damage of 3D woven composites were experimentally and numerically investigated, considering different off-axis angles and impact energies. The impact responses were examined ...by LVI tests, and the damage morphology inside the composites was observed by X-ray micro-computed tomography (μ-CT). Yarn-level damage evolution was revealed by developing a hybrid finite element analysis model. The results show that the impact damage has significant directionality determined by the weft/warp orientation of the composites. The damage originates at the bottom of the impacted area and then expands outwards and upwards simultaneously, accompanied by in-plane and out-of-plane stress transfers. The straight-line distributed weft/warp yarns play an important role in bearing loads at the beginning of loading, while the w-shape distributed binder warp yarns gradually absorb impact deformation and toughen the whole structure as the loading proceeds. The effect of directional impact damage on post-impact performance was explored by performing compressing-after-impact (CAI) tests. It is revealed that the CAI properties along principal directions are more sensitive to the low-velocity impact, and the damage mode is significantly affected by the loading direction.
Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously ...identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.
This paper considered the groundwater head fluctuation induced by tide and pumping in the coastal multi-layered aquifer system. The multi-layered aquifer system comprises an unconfined aquifer, an ...upper confined aquifer, and a lower confined aquifer. An aquiclude exists between each two aquifers. All the layers terminate at the coastline. The new analytical solutions describing groundwater head variation in the coastal multi-confined aquifer system are derived. Superposition principle and image methods are used for the derivation of the analytical solutions. Analytical solutions of different situations of without considering pumping, of without considering tidal effect, and of N -layered confined aquifers are also derived. The impacts of the parameters of the initial phase shift of tide, pumping rate, position of the pumping well, storage coefficient, and transmissivity on the groundwater head fluctuation are discussed. The analytical solutions are applied with application examples in fitting field observations and parameter estimations. The estimated values of the hydraulic conductivities in the upper and lower confined aquifers are within the range of the values obtained from the field experiments. The fitted results of the analytical solutions capture the main characteristics of groundwater head fluctuation affected by the tide and groundwater pumping. The study of groundwater head fluctuation in the coastal zone is helpful to understand the mechanism of seawater intrusion under the influence of tide and groundwater pumping.
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