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In this study, the influence of cyclic thermal loading on the mechanical response of an energy pile installed in saturated clay subjected to sustained combined axial/horizontal mechanical loading was investigated using physical modelling. After completion of the soil saturation process and prior to starting the thermo-mechanical loading, the pile fixation was released inducing pile head heave. When the rate of pile head heave became small, the model pile was subjected to compression axial loading of 100 N (i.e. 20% of the estimated ultimate axial load) followed by horizontal loading of 35, 71 and 109 N (corresponding to accumulative pile head horizontal displacements of 4, 7 and 12% of pile diameter) before subsequent 15 heating–cooling cycles. The results indicated that imposing heating–cooling cycles to the pile resulted in irreversible horizontal displacement, accumulating at a reducing rate as the number of thermal cycles increased. By the end of the 15th cycle, the accumulated irreversible horizontal displacement was estimated at 0·57, 1·15 and 1·84% of pile diameter under the horizontal loads of 35, 71 and 109 N, respectively. Reversely, thermally induced pile head axial displacement at the end of the 15th cycle is practically insignificant (smaller than 0·1% of pile diameter).

Hypoxia can cause basement membrane (BM) degradation in tissues. Matrix metalloproteinase 9 (MMP-9) is involved in various human cancers as well as BM degradation by downregulating type IV collagen (COL4). This study investigated the role of MMP-9 in hypoxia-mediated BM degradation in rat bone marrow based on its regulation of collagen type IV alpha 1 chain (COL4A1). Eighty male rats were randomly divided into four groups based on exposure to hypoxic conditions at a simulated altitude of 7,000 m, control (normoxia) and 3, 7, and 10 days of hypoxia exposure. BM degradation in bone marrow was determined by transmission electron microscopy. MMP-9 levels were assessed by western blot and real-time PCR, and COL4A1 levels were assessed by western blot and immunohistochemistry. Microvessels BMs in bone marrow exposed to acute hypoxia were observed by electron microscopy. MMP-9 expression increased, COL4A1 protein expression decreased, and BM degradation occurred in the 10-, 7-, and 3-day hypoxia groups compared with that in the control group (all P < 0.05). Hypoxia increased MMP-9 levels, which in turn downregulated COL4A1, thereby increasing BM degradation. MMP-9 upregulation significantly promoted BM degradation and COL4A1 downregulation. Our results suggest that MMP-9 is related to acute hypoxia-induced BM degradation in bone marrow by regulating COL4A1.

Background Chronic rhinosinusitis (CRS) and eosinophilic esophagitis (EoE) are immune-mediated inflammatory conditions that share common histopathologic features. Once considered two separate pathologies, preliminary data has suggested that a higher prevalence of EoE may exist in patients with CRS. Objectives We aimed to expand the base of evidence across geographic regions and investigate the association between EoE and CRS, including CRS with nasal polyposis (CRSwNP). Methods Quantitative data detailing the prevalence of CRS, CRSwNP, and EoE were pooled from 6 large academic institutions spread across the United States using Epic electronic medical record system. One-way analysis of variance was then used to analyze the data. Results The mean prevalence of EoE in our general population sample of over 26 million individual records was 0.058% (range, 0.013%-0.103%). The mean prevalence of EoE in our sub-populations of individual with diagnoses of CRS and CRSwNP was 0.43% (F(1,12) = [8.194], P = .01) and 0.84% (F(1,12) = [23.61], P Conclusion This study reveals an 8-fold greater prevalence of concurrent EoE in patients with CRS. Importantly, this is the first study to describe the association of EoE and the CRSwNP subtype, and we demonstrate a 14-fold greater prevalence of EoE in patients with CRSwNP.

Background and Objective This study aims to evaluate the medicolegal trends related to 2 common orbital surgeries: orbital decompression and dacryocystorhinostomy (DCR). These procedures are performed by ophthalmologists, otolaryngologists, and multidisciplinary teams of both specialists. Methods The Westlaw database was reviewed from 1980 to 2020 for medical malpractice cases involving orbital decompression and DCR surgeries. Data were compiled on plaintiff and defendant demographics, procedure performed, legal allegation, nature of injury, and verdict or settlement awards. The Ophthalmic Mutual Insurance Company was also queried for all malpractice cases pertaining to orbital decompression and DCR from 1995 to 2021. Results The Westlaw database included 60 cases (34 orbital decompression, 26 DCR); of these, 8 orbital decompression and 6 DCR cases met inclusion criteria. Of the 7 orbital decompression cases that were tried, a verdict in favor of the plaintiff occurred in 4 cases (57%). Of the 5 DCR cases that were tried, a verdict in favor of the plaintiff occurred in 2 cases (40%). A search of all claims at OMIC yielded 31 cases (15 orbital decompression, 16 DCR). 22 of 31 cases were either dismissed or resulted in no payment. The remainder was settled out of court, with only one case being tried and the verdict supporting the defendant. Conclusion Despite several thousand orbital decompressions and DCR surgeries being performed annually in the US, very few lawsuits involving these complex surgeries have gone to trial. However, of the cases that did go to trial, a relatively high proportion of verdicts for plaintiffs was observed.

Objective/hypothesisTo investigate the clinical features, management strategies and outcomes for patients with metastatic primary skull base chordomas.Study designSystematic review.MethodsA systematic search through Pubmed/Medline, Web of Science, and EBSCOhost (CINAHL) was conducted without restriction on dates. After study screening and full-text assessment, two authors independently extracted all data using a pre-established abstraction form.ResultsForty cases were included from 38 studies. The average age (standard deviation [SD]) of the sample at presentation was 28.5 (23.3) and was equally distributed across genders. The average time (SD) between initial diagnosis to local recurrence was 40.1 (60.3) months. The average time (SD) from primary tumor detection to the diagnosis of metastatic disease was 55.2 (49.0) months. The most common subsite for metastatic spread were the lungs (32.5%). Of the 33 patients with data on outcomes, 48.5% were found to have expired by the time of publication. The median overall survival was estimated to be 84 months (95% confidence interval [CI] 62.3-105.7).ConclusionsThe most common subsites for metastatic spread of skull base chordoma were the lungs and bone. Overall survival for patients in the current cohort was a median of 84 months, with no significant differences noted when stratifying by the extent of surgery or the site of metastases.Level of evidence3a.

This research aims to determine the total economic value of mangrove forests on Bengkalis Island, Bengkalis Regency, Indonesia. Data collection in the field was done through observation and interviews. The research was carried out from October 2020 to March 2021. The results showed that the total economic value of mangrove forests was US$ 5.8 million per year. This study uses Total Economic Value (TEV) as a framework for estimating the value of the benefits of mangrove forests in Bengkalis. In addition, another value taken into account in this study is the function of mangroves as abrasion barrier, barrier to seawater intrusion, and a provider of nutrients for marine biota. The results of this study underscore the importance of mangrove ecosystems for the economy of coastal areas.

Osteoradionecrosis (ORN) of the skull base and craniovertebral junction is a challenging complication of radiation therapy (RT). Severe cases often require surgical intervention through a multi-modal approach. With the evolution in endoscopic surgery and advances in skull base reconstruction, there is an increasing role for microvascular free tissue transfer (MFTT). We describe an endoscopic-assisted approach for the management of ORN of the skull base using fascia lata for MFTT.Retrospective case series.Between 2017 and 2021, a review of all cases in which fascia lata MFTT was utilized for skull base ORN was performed. Patient demographics, preoperative characteristics, and postoperative outcomes with long-term follow-up were reviewed.Five patients were identified. Mean duration to onset of ORN was 17 months following RT. A trial of antibiotics, hyperbaric oxygen (HBO), and/or limited debridement was attempted without success. Refractory pain and progressive osteomyelitis were unifying symptoms. All patients underwent endoscopic debridement of the affected region of ORN prior to MFTT. Vascularized fascia lata was inset through a combined endonasal and transoral corridor. There was improvement in chronic pain in the postop setting with no patients requiring continued antibiotics or HBO therapy. Mean post-op follow-up was 23 months.With continued evolution in endoscopic, minimally invasive approaches, there is an expanding indication for early surgical management in refractory ORN. Fascia lata MFTT is a novel and effective strategy for the management of ORN of the skull base and upper cervical spine with excellent postoperative outcomes and limited patient morbidity.4 Laryngoscope, 2022.

This retrospective case-control study evaluated the diagnostic performance of a commercially available chest radiography deep convolutional neural network (DCNN) in identifying the presence and position of central venous catheters, enteric tubes, and endotracheal tubes, in addition to a subgroup analysis of different types of lines/tubes. A held-out test dataset of 2568 studies was sourced from community radiology clinics and hospitals in Australia and the USA, and was then ground-truth labelled for the presence, position, and type of line or tube from the consensus of a thoracic specialist radiologist and an intensive care clinician. DCNN model performance for identifying and assessing the positioning of central venous catheters, enteric tubes, and endotracheal tubes over the entire dataset, as well as within each subgroup, was evaluated. The area under the receiver operating characteristic curve (AUC) was assessed. The DCNN algorithm displayed high performance in detecting the presence of lines and tubes in the test dataset with AUCs > 0.99, and good position classification performance over a subpopulation of ground truth positive cases with AUCs of 0.86–0.91. The subgroup analysis showed that model performance was robust across the various subtypes of lines or tubes, although position classification performance of peripherally inserted central catheters was relatively lower. Our findings indicated that the DCNN algorithm performed well in the detection and position classification of lines and tubes, supporting its use as an assistant for clinicians. Further work is required to evaluate performance in rarer scenarios, as well as in less common subgroups.

Soil Organic Carbon (SOC) turnover t in wetlands and the corresponding governing processes are still poorly represented in numerical models. t is a proxy to the carbon storage potential in each SOC pool and C fluxes within the whole ecosystem; however, it has not been comprehensively quantified in wetlands globally. Here, we quantify the turnover time t of various SOC pools and the governing biotic and abiotic processes in global wetlands using a comprehensively tested process-based biogeochemical model. Globally, we found that t ranges between 1 and 1,000 years and is controlled by anaerobic (in 78% of global wetlands area) and aerobic (15%) respiration, and by abiotic destabilization from soil minerals (5%). t in the remaining 2% of wetlands is controlled by denitrification, sulfur reduction, and leaching below the subsoil. t can vary by up to one order of magnitude in temperate, continental, and polar regions due to seasonal temperature and can shift from being aerobically controlled to anaerobically controlled. Our findings of seasonal variability in SOC turnover suggest that wetlands are susceptible to climate-induced shifts in seasonality, thus requiring better accounting of seasonal fluctuations at geographic scales to estimate C exchanges between land and atmosphere.

Accurate radiologic evaluation of the possibility of successful recanalization in symptomatic chronic ICA occlusion remains challenging. This study aimed to investigate the high-resolution MR imaging characteristics of symptomatic chronic ICA occlusion and their association with successful recanalization.Consecutive patients with symptomatic chronic ICA occlusion who underwent balloon dilation plus stent implantation were identified retrospectively and divided into 2 groups: a successful recanalization group and an unsuccessful recanalization group. Clinical and high-resolution MR imaging characteristics were compared between the groups. Univariate and multivariate analyses were used to identify the characteristics associated with successful recanalization.A total of 114 patients were included in the study. High-resolution MR imaging characteristics independently associated with unsuccessful recanalization were longer lesion length (OR, 0.41; 95% CI, 0.36-0.55;In symptomatic chronic ICA occlusion, lesion length and calcification volume (for proximal occlusion), the level of reversed distal ICA flow, and the lumen area (for distal occlusion) appear to be predictors of successful recanalization. High-resolution MR imaging can evaluate chronic ICA occlusion and help in clinical decision-making.

Purpose: To recognize the novel finding of a bacillary layer detachment (BALAD) secondary to endogenous fungal endophthalmitis. Methods: Chart review, literature review. Results: BALAD is a recently described condition in which the photoreceptor layer splits at the level of the inner segment myoid. We describe a case of BALAD associated with endogenous fungal endophthalmitis and subsequent development of choroidal neovascularization, although it is unclear if BALAD contributed to neovessel formation. Conclusions: BALAD is generally seen in the setting of inflammatory or infectious retinal diseases. This is the first report of BALAD secondary to endogenous fungal endophthalmitis.

Numerous data demonstrate that global climate change affects crop yield and quality. However, the effect of climate change on the nutritive value of forage crops remains unclear. Oat grass (Avena sativa L.) was used as a representative forage crop to understand changes in yield and chemical composition. The growth of oat grass under elevated temperature and CO

The aim of this study was to analyze the effects of different salinities on osmotic performance rate, growth performance, and oxygen consumption rate Pangasianodon hypophthalmus. The method used is an experimental method by applying a completely randomized design (CRD) with four treatments, salinity 0 ppt, salinity 5 ppt, salinity 7 ppt, and salinity 9 ppt. The fish specimen used is 8 cm in length, weighing 4 g, were raised in a 54 L tank containing 40 L of water at a density of 1 fish 2 L-1 and kept for 45 days. Feed with commercial pellet 3 times a day in at satiation. The treatment with 5 ppt salinity showed the best effects, yielding an osmotic performance rate of 21,66 mOsm/I H2O, absolute weight growth of 9,63 g, the absolute length of 3.54 cm, the specific growth rate of 2,99 %, the oxygen consumption rate of 0,410 mgO2/g body weight/hour and survival rate 100 %. The water quality is at a level suitable for the growth of P. hypophthalmus. It was concluded that 5 ppt salinity can minimize the value of the osmotic performance rate, increase growth rates, minimize the level of oxygen consumption and increase

Nitryl chloride (ClNO2), an important precursor of Cl atoms, significantly affects atmospheric oxidation capacity and O3 formation. However, sources of ClNO2 in inland China have not been fully elucidated. In this work, laboratory experiments were conducted to investigate heterogeneous reactions of N2O5 with eight saline mineral dust samples collected from different regions in China, and substantial formation of ClNO2 was observed in these reactions. ClNO2 yields, φ(ClNO2), showed large variations (ranging from to ∼0.77) for different saline mineral dust samples, depending on mass fractions of particulate chloride. In addition, φ(ClNO2) could increase, decrease or show insignificant change for different saline mineral dust samples when relative humidity (RH) increased from 18 % to 75 %. We further found that current parameterizations significantly overestimated φ(ClNO2) for heterogeneous uptake of N2O5 onto saline mineral dust. In addition, assuming a uniform φ(ClNO2) value of 0.10 for N2O5 uptake onto mineral dust, we used a 3-D chemical transport model to assess the impact of this reaction on tropospheric ClNO2 in China and found that weekly mean nighttime maximum ClNO2 mixing ratios could have been increased by up to 85 pptv during a severe dust event in May 2017. Overall, our work showed that heterogeneous reaction of N2O5 with saline mineral dust could be an important source of tropospheric ClNO2 in inland China.

Despite recent advancements in cloud processing and modelling and the increasing availability of high spectral- and temporal- resolution satellite imagery, mapping the spatial distribution of crop types remains a challenging task. Here, we present CROPGRIDS – a comprehensive global, geo-referenced dataset providing information on areas for 173 crops circa the year 2020, at a resolution of 0.05° (~5.55 km at the equator). It represents a major update of the Monfreda et al. (2008) dataset, the most widely used geospatial dataset previously available, covering 175 crops with reference year 2000 at 10 km spatial resolution. CROPGRIDS updates Monfreda et al. (2008) through the careful evaluation of 26 published gridded datasets covering more recent crop information at regional, national, and global levels, largely over the period 2015–2020. The new product successfully updates the area extent for 80 of the 175 crops originally covered, representing an update to 1.2 billion hectares of crop area (i.e., 81 % of the total cropland included in CROPGRIDS). CROPGRIDS carries forward the crop type maps originally in Monfreda et al. (2008) for 93 crops as more recent information for these crops is not available. We compared CROPGRIDS harvested area of individual crops against independent national and subnational data from 36 National Statistical Offices (NSOs), national-level crop area data for more than 180 countries and territories from FAOSTAT, as well as geospatially, against a newly available high-resolution (30 m) cropland agreement map (Tubiello et al., 2023). Results indicated robustness against the available independent information, with CROPGRIDS world total harvested and crop areas around 1.5 billion hectares. To the best of our knowledge, CROPGRIDS represents the most comprehensive update of previous work on the subject area, offering a new benchmark of global gridded harvested and crop area data for the year circa 2020. CROPGRIDS dataset can be downloaded at https://doi.org/10.6084/m9.figshare.22491997 (Tang et al., 2023).

PDF file - 39K, HT29 PLX4720 resistant clone was treated with EGFR siRNA for 48 h, and then treated with 1�M PLX4720 for further two weeks. EGFR knockdown reduced sensitivity to PLX4720 by numbers of formed colonies (# P

PDF file - 30K, BRAF mutant cell lines utilized in the RPPA analysis. Cells were lysed at approximately 70% confluence in 10% serum. Of note, Colo201 and Colo205 are derived from the same colon cancer patient, as are HT29 and WiDr. Cell lines were obtained from the American Type Culture Collection, or the Ludwig Institute of Cancer Research. Cell line identities were confirmed by STR testing, and were verified to be Mycoplasma-free. All lines were grown in DMEM/F-12, or RPMI1640 medium supplemented with 10% FBS and 2 mmol/L glutamine or MEM, (10�S, sodium pyruvate, L-glutamine, vitamins, and nonessential amino acids). Cells were incubated in 5% CO2 at 37{degree sign}C.

PDF file - 338K, Cells were incubated for 24h (HT29, Colon205) or 48 h (RKO) with PLX4720 (1 M for all cell lines), LY294002 (15 M for all cell lines) or their combination. Cells were then harvested and stained with propidium iodide. DNA concentrations were measured by FACS. The data represent mean values from three independent experiments. (# represents P < 0.01)

Supplementary Data from Prevalence of TMPRSS2-ERG Fusion Prostate Cancer among Men Undergoing Prostate Biopsy in the United States

PDF file - 36K, Cells were treated with PTEN siRNA for 48 h, and then treated with PLX4720 at doses near the individual IC50s for a further 72 h. (HT29: 0.01�M, Colo205: 0.05�M, Vaco5: 1 �M). HT29 contains an atypical and poorly characterized mutation (P449T) outside of the hotspots in the kinase and helical domains. siPTEN did not impact PLX4720 sensitivity in Vaco5, which contains a known activating mutation in the helical domain of PIK3CA.

Purpose: Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen–screened men undergoing prostate biopsy in the United States.Experimental Design: We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable.Results:ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion–positive prostate cancer biopsies than gene fusion–negative prostate cancer biopsies (P ≤ 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02).Conclusions: This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.

PDF file - 44K, The combination therapy with PLX4720 and azacytidine was repeated in HT29 cells first treated with siRNA to PTEN . Silencing PTEN was not sufficient to fully abolish the synergy seen with the combination (* P

Purpose: Vemurafenib, a selective inhibitor of BRAFV600, has shown significant activity in BRAFV600 melanoma but not in less than 10% of metastatic BRAFV600 colorectal cancers (CRC), suggesting that studies of the unique hypermethylated phenotype and concurrent oncogenic activation of BRAFmut CRC may provide combinatorial strategies.Experimental Design: We conducted comparative proteomic analysis of BRAFV600E melanoma and CRC cell lines, followed by correlation of phosphoinositide 3-kinase (PI3K) pathway activation and sensitivity to the vemurafenib analogue PLX4720. Pharmacologic inhibitors and siRNA were used in combination with PLX4720 to inhibit PI3K and methyltransferase in cell lines and murine models.Results: Compared with melanoma, CRC lines show higher levels of PI3K/AKT pathway activation. CRC cell lines with mutations in PTEN or PIK3CA were less sensitive to growth inhibition by PLX4720 (P = 0.03), and knockdown of PTEN expression in sensitive CRC cells reduced growth inhibition by the drug. Combined treatment of PLX4720 with PI3K inhibitors caused synergistic growth inhibition in BRAF-mutant CRC cells with both primary and secondary resistance. In addition, methyltransferase inhibition was synergistic with PLX4720 and decreased AKT activation. In vivo, PLX4720 combined with either inhibitors of AKT or methyltransferase showed greater tumor growth inhibition than PLX4720 alone. Clones with acquired resistance to PLX4720 in vitro showed PI3K/AKT activation with EGF receptor (EGFR) or KRAS amplification.Conclusions: We show that activation of the PI3K/AKT pathway is a mechanism of both innate and acquired resistance to BRAF inhibitors in BRAFV600E CRC and suggest combinatorial approaches to improve outcomes in this poor prognosis subset of patients. Clin Cancer Res; 19(3); 657–67. ©2012 AACR.