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Video Abstract1_mjzbyt8dKaltura

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Abstract: Purpose: The colon coordinates fecal elimination while reabsorbing excess fluid. Extended colonic resection removes synchronous and prevents metachronous disease but may adversely alter bowel function and health-related quality of life to a greater degree than segmental resection. This study examined the short-term morbidity and long-term function and quality of life after colon resections of different extents. Methods: Patients undergoing extended resections (n = 201, subtotal colectomy with ileosigmoid or total abdominal colectomy with ileorectal anastomosis) and segmental colonic resections (n = 321) during 1991 to 2003 were reviewed for perioperative outcomes and surveyed for bowel function and quality of life using an institutional questionnaire and a validated quality of life instrument (response rate: 70 percent). Results: The most common indication for extended resections was multiple polyps, and for segmental resections, single malignancy. The complication-free rate was 75.4 percent after segmental resections, 42.8 percent after ileosigmoid anastomosis, and 60 percent after ileorectal anastomosis. Median daily stool frequency was two after segmental resections, four after ileosigmoid anastomosis, and five after ileorectal anastomosis, despite considerable dietary restrictions (55.6 percent) and medication use (19.6 percent daily) after ileorectal anastomosis. Significant proportions of patients felt restricted from preoperative social activity (31.5 percent), housework (20.4 percent), recreation (31.5 percent), and travel (42.6 percent) after ileorectal anastomosis. The overall quality of life after segmental resection, ileosigmoid anastomosis, and ileorectal anastomosis was 98.5, 94.9, and 91.2, respectively. Conclusions: Measurable compromises in long-term bowel function and quality of life were observed after extended vs. segmental resections. The relative differences in patient-related outcomes should be deliberated against the clinical benefits of extended resection for the individual patient.

Introduction: Dental caries remains one of the most prevalent but preventable diseases among children worldwide and especially affects children with a lower socioeconomic status or ethnic minority background. It is important that all groups of children are reached by preventive interventions to reduce oral health inequalities. So far, it is unknown whether children from different social and ethnic groups benefit equally from potentially effective oral health interventions.Objectives: This scoping review aimed to identify European public health interventions that report their effect on dental caries across different social groups.Methods: Four databases were searched for studies evaluating the effect of oral health interventions on dental caries among children from 0 to 12 y, and studies were included when results were presented by children of different social groups separately.Results: A total of 14 studies were included, representing 4 different countries: 3 randomized and 11 nonrandomized studies. Most studies were performed at schools. Six studies showed results indicative of a reduction in oral health inequalities, 4 studies showed results that potentially widen oral health inequalities, and 5 studies showed results that were indicative of no impact on oral health inequalities. Interventions that contain early approaches, with a high frequency, approaching multiple levels of influence, and including at least the broader organizational or public policy level, may have the potential to reduce oral health inequalities among children from birth to young adolescence.Conclusion: We recommend researchers to perform high-quality intervention studies and to evaluate the effectiveness of oral health intervention always in different socioeconomic or ethnic groups separately, to better understand their contribution toward oral health (in)equalities.Knowledge Transfer Statement: This review offers insight in the differential effects that oral health interventions might have across different social groups. Its results can be used to develop interventions that might reduce oral health inequalities among children. Also, we recommend future researchers to always evaluate the effects of any preventive oral health measure in different social groups separately.

Background Chemotherapy is associated with postoperative ventral incisional hernia (PVIH) after right hemicolectomy (RHC) for colon cancer, and abdominal wall closure technique may affect PVIH. We sought to identify clinical predictors of PVIH.Methods We retrospectively analyzed patients who underwent RHC for colon cancer from 2008-2018 and later developed PVIH. Time to PVIH was analyzed with Kaplan-Meier analysis, clinical predictors were identified with multivariable Cox proportional hazards modeling, and the probability of PVIH given chemotherapy and the suture technique was estimated with Bayesian analysis.Results We identified 399 patients (209 no adjuvant chemotherapy and 190 adjuvant chemotherapy), with an overall PVIH rate of 38%. The 5-year PVIH rate was 55% for adjuvant chemotherapy, compared with 38% for none (log-rank P < .05). Adjuvant chemotherapy (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.18-2.31, P< .01), age (HR .99, 95% CI .97-1.00, P< .01), body mass index (HR 1.02, 95% CI 1.00-1.04, P< .01), and neoadjuvant chemotherapy (HR 1.92, 95% CI 1.21-3.00, P< .01) were independently associated with PVIH. Postoperative ventral incisional hernia was more common overall in patients who received adjuvant chemotherapy (46% compared with 30%, P< .01). In patients who received adjuvant chemotherapy, the probability of PVIH for incision closure with #1 running looped polydioxanone was 42%, compared with 59% for incision closure with #0 single interrupted polyglactin 910.Discussion Exposure to chemotherapy increases the probability of PVIH after RHC, and non–short stitch incision closure further increases this probability, more so than age or body mass index. The suture technique deserves further study as a modifiable factor in this high-risk population.

We designed a prospective feasibility study to assess the 5x-multiplier (5x) calculation (eg, 3 pills in last 24 hours × 5 = 15) to standardize discharge opioid prescriptions compared to usual care.

Orthogonal frequency-division multiple access (OFDMA), which is a combination of orthogonal frequency division multiplexing (OFDM) with frequency-division multiple access (FDMA), is regarded as a promising solution for enhancing the performance of interactive broadcasting wireless systems. This paper presents our investigation for the impacts of symbol timing errors and peak-to-average power ratio (PAR) on OFDMA-based interactive broadcasting systems. Under the condition of the same side information bits, the selective mapping (SLM) approach can be implemented by decimating OFDM samples, which is less complex compared to the ordinary SLM incurring a slight degradation of the PAR performance. Including the effects of clipping operation and symbol timing misalignment, the bit error rate (BER) performance is investigated for a typical OFDMA uplink scenario. Index Terms--Broadcasting, OFDM, OFDMA, selective mapping, peak-to-average power ratio, symbol timing error

IMPORTANCE: Total neoadjuvant therapy (TNT) is often used to downstage locally advanced rectal cancer (LARC) and decrease locoregional relapse; however, more than one-third of patients develop recurrent metastatic disease. As such, novel combinations are needed. OBJECTIVE: To assess whether the addition of pembrolizumab during and after neoadjuvant chemoradiotherapy can lead to an improvement in the neoadjuvant rectal (NAR) score compared with treatment with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and chemoradiotherapy alone. DESIGN, SETTING, AND PARTICIPANTS: In this open-label, phase 2, randomized clinical trial (NRG-GI002), patients in academic and private practice settings were enrolled. Patients with stage II/III LARC with distal location (cT3-4 ≤ 5 cm from anal verge, any N), with bulky disease (any cT4 or tumor within 3 mm of mesorectal fascia), at high risk for metastatic disease (cN2), and/or who were not candidates for sphincter-sparing surgery (SSS) were stratified based on clinical tumor and nodal stages. Trial accrual opened on August 1, 2018, and ended on May 31, 2019. This intent-to-treat analysis is based on data as of August 2020. INTERVENTIONS: Patients were randomized (1:1) to neoadjuvant FOLFOX for 4 months and then underwent chemoradiotherapy (capecitabine with 50.4 Gy) with or without intravenous pembrolizumab administered at a dosage of 200 mg every 3 weeks for up to 6 doses before surgery. MAIN OUTCOMES AND MEASURES: The primary end point was the NAR score. Secondary end points included pathologic complete response (pCR) rate, SSS, disease-free survival, and overall survival. This report focuses on end points available after definitive surgery (NAR score, pCR, SSS, clinical complete response rate, margin involvement, and safety). RESULTS: A total of 185 patients (126 [68.1%] male; mean [SD] age, 55.7 [11.1] years) were randomized to the control arm (CA) (n = 95) or the pembrolizumab arm (PA) (n = 90). Of these patients, 137 were evaluable for NAR score (68 CA patients and 69 PA patients). The mean (SD) NAR score was 11.53 (12.43) for the PA patients (95% CI, 8.54-14.51) vs 14.08 (13.82) for the CA patients (95% CI, 10.74-17.43) (P = .26). The pCR rate was 31.9% in the PA vs 29.4% in the CA (P = .75). The clinical complete response rate was 13.9% in the PA vs 13.6% in the CA (P = .95). The percentage of patients who underwent SSS was 59.4% in the PA vs 71.0% in the CA (P = .15). Grade 3 to 4 adverse events were slightly increased in the PA (48.2%) vs the CA (37.3%) during chemoradiotherapy. Two deaths occurred during FOLFOX: sepsis (CA) and pneumonia (PA). No differences in radiotherapy fractions, FOLFOX, or capecitabine doses were found. CONCLUSIONS AND RELEVANCE: Pembrolizumab added to chemoradiotherapy as part of total neoadjuvant therapy was suggested to be safe; however, the NAR score difference does not support further study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02921256

ObjectivePatients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making an ideal target for cancer prevention. Our objective was to evaluate the safety, assess the activity and discover novel molecular pathways involved in the activity of naproxen as primary and secondary chemoprevention in patients with LS.DesignWe conducted a Phase Ib, placebo-controlled, randomised clinical trial of two dose levels of naproxen sodium (440 and 220 mg) administered daily for 6 months to 80 participants with LS, and a co-clinical trial using a genetically engineered mouse model of LS and patient-derived organoids (PDOs).ResultsOverall, the total number of adverse events was not different across treatment arms with excellent tolerance of the intervention. The level of prostaglandin E2 in the colorectal mucosa was significantly decreased after treatment with naproxen when compared with placebo. Naproxen activated different resident immune cell types without any increase in lymphoid cellularity, and changed the expression patterns of the intestinal crypt towards epithelial differentiation and stem cell regulation. Naproxen demonstrated robust chemopreventive activity in a mouse co-clinical trial and gene expression profiles induced by naproxen in humans showed perfect discrimination of mice specimens with LS and PDOs treated with naproxen and control.ConclusionsNaproxen is a promising strategy for immune interception in LS. We have discovered naproxen-induced gene expression profiles for their potential use as predictive biomarkers of drug activity.Trial registration numbergov Identifier: NCT02052908

An increasing number of studies are describing potential uses of circulating tumour DNA (ctDNA) in the care of patients with colorectal cancer. Owing to this rapidly developing area of research, the Colon and Rectal–Anal Task Forces of the United States National Cancer Institute convened a panel of multidisciplinary experts to summarize current data on the utility of ctDNA in the management of colorectal cancer and to provide guidance in promoting the efficient development and integration of this technology into clinical care. The panel focused on four key areas in which ctDNA has the potential to change clinical practice, including the detection of minimal residual disease, the management of patients with rectal cancer, monitoring responses to therapy, and tracking clonal dynamics in response to targeted therapies and other systemic treatments. The panel also provides general guidelines with relevance for ctDNA-related research efforts, irrespective of indication.

We use the Insight-HXMT data collected during the 2019 outburst from X-ray pulsar 4U 1901+03 to complement the orbital parameters reported by Fermi/GBM. Using the Insight-HXMT, we examine the correlation between the derivative of the intrinsic spin frequency and bolometric flux based on accretion torque models. It was found that the pulse profiles significantly evolve during the outburst. The existence of two types of the profile's pattern discovered in the Insight-HXMT data indicates that this source experienced transition between a super-critical and a sub-critical accretion regimes during its 2019 outburst. Based on the evolution of the pulse profiles and the torque model, we derive the distance to 4U 1901+03 as 12.4±0.2kpc.

We study the 2018 outburst of Aql X-1 via the monitor of all sky X-ray image (MAXI) data. We show that the outburst starting in February 2018 is a member of short-lowclass in the frame of outburst duration and the peak count rate although the outburst morphology is slightly different from the other fast-rise-exponential-decay (FRED) type outbursts with a milder rising stage. We study the partial accretion in the weak propeller stage of Aql X-1 via the MAXI data of the 2018 outburst. We report on the spectral analysis of 3 observations of Aquila X-1 obtained by Insight – hard X-ray modulation telescope (Insight-HXMT) during the late decay stage of the 2018 outburst. We discuss that the data taken by Insight-HXMT is just after the transition to the weak propeller stage. Our analysis shows the necessity of a comptonization component to take into account the existence of an electron cloud resulting photons partly up-scattered.

We present a detailed timing study of the brightest persistent X-ray source Sco X-1 using the data collected by the Hard X-ray Modulation Telescope (Insight-HXMT) from July 2017 to August 2018. A complete Z-track hardness-intensity diagram (HID) is obtained. The normal branch oscillations (NBOs) at ∼ 6 Hz in the lower part of the normal branch (NB) and the flare branch oscillations (FBOs) at ∼ 16 Hz in the beginning part of the flaring branch (FB) are found in observations with the Low Energy X-ray Telescope (LE) and the Medium Energy X-ray Telescope (ME) of Insight-HXMT, while the horizontal branch oscillations (HBOs) at ∼ 40 Hz and the kilohertz quasi-periodic oscillations (kHz QPOs) at ∼ 800 Hz are found simultaneously above 20 keV for the first time on the horizontal branch (HB) by the High Energy X-ray Telescope (HE) and ME. We find that for all types of the observed QPOs, the centroid frequencies are independent of energy, while the root mean square (rms) increases with energy; the centroid frequencies of both the HBOs and kHz QPOs increase along the Z-track from the top to the bottom of the HB; and the NBOs show soft phase lags increasing with energy. A continuous QPO transition from the FB to NB in ∼ 200 s are also detected. Our results indicate that the non-thermal emission is the origin of all types of QPOs, the innermost region of the accretion disk is non-thermal in nature, and the corona is nonhomogeneous geometrically.

A new black hole X-ray binary (BHXRB) MAXI J1535-571 was discovered by MAXI during its outburst in 2017. Using observations taken by the first Chinese X-ray satellite, the Hard X-ray Modulation Telescope (dubbed as Insight-HXMT), we perform a joint spectral analysis (2-150 keV) in both energy and time domains. The energy spectra provide the essential input for probing the intrinsic Quasi-Periodic Oscillation (QPO) fractional rms spectra (FRS). Our results show that during the intermediate state, the energy spectra are in general consistent with those reported by Swift/XRT and NuSTAR. However, the QPO FRS become harder and the FRS residuals may suggest the presence of either an additional power-law component in the energy spectrum or a turn-over in the intrinsic QPO FRS at high energies.

We congratulate Dr. Weiser and colleagues for an excellent and concise review of the approaches available for colorectal cancer patients with a limited number of metastases, defined as 'oligometastatic disease.' [...]

The evidences for the influence of thermonuclear (type-I) X-ray bursts upon the surrounding environments in neutron star low-mass X-ray binaries (LMXB) were detected previously via spectral and timing analyses. Benefitting from a broad energy coverage of Insight-HXMT, we analyze one photospheric radius expansion (PRE) burst, and find an emission excess at soft X-rays. Our spectral analysis shows that, such an excess is not likely relevant to the disk reflection induced by the burst emission and can be attributed to an enhanced pre-burst/persistent emission. We find that the burst and enhanced persistent emissions sum up to exceed Eddington luminosity by ∼ 40 percentages. We speculate that the enhanced emission is from a region beyond the PRE radius, or through the Comptonization of the corona.

Graphene oxide (GO) offers excellent multifunctional properties with potential for applications. The applicability depends on the stability of GO suspensions in different mediums. Herein, we report a systematic study of cation-induced coagulation phenomenon in GO suspension in water. We have investigated the morphology of coagulated GO, coagulation degree of GO suspensions, and the factors affecting coagulation process. Our study suggests that the coagulation of GO depends on concentration of cations, surface charge, and coordination bond energy of cations introduced into the suspensions. This study helps us understand the coagulation phenomenon in GO suspension, and it will be helpful in preparing GO with 3-dimensional porous structure with improved surface area for applications.

In the U.S., colorectal cancer (CRC) has become the second most incident cancer among adults younger than age 50, and is a leading contributor to cancer deaths in this age group. Young-onset CRC is a heterogeneous disease entity that encompasses etiologies arising from a mix of genetic and environmental factors. Germline predisposition through major hereditary cancer syndromes account for 10–19% of these patients, while familial clustering of risk can be observed in another 23%. The majority of the patients have sporadic CRCs that predominate the left colon and rectum and are typically already nodally or systemically metastatic at diagnosis. The key components of their management include multidisciplinary oncologic care, clinical genetics care, and multidimensional survivorship care. We herein review the epidemiology, the etiologies, and other considerations surrounding the diagnosis and treatment of young-onset CRC.

IMPORTANCE: Colorectal carcinomas in patients with Lynch syndrome (LS) arise in a background of mismatch repair (MMR) deficiency, display a unique immune profile with upregulation of immune checkpoints, and response to immunotherapy. However, there is still a gap in understanding the pathogenesis of MMR-deficient colorectal premalignant lesions, which is essential for the development of novel preventive strategies for LS. OBJECTIVE: To characterize the immune profile of premalignant lesions from a cohort of patients with LS. DESIGN, SETTING, AND PARTICIPANTS: Whole-genome transcriptomic analysis using next-generation sequencing was performed in colorectal polyps and carcinomas of patients with LS. As comparator and model of MMR-proficient colorectal carcinogenesis, we used samples from patients with familial adenomatous polyposis (FAP). In addition, a total of 47 colorectal carcinomas (6 hypermutants and 41 nonhypermutants) were obtained from The Cancer Genome Atlas (TCGA) for comparisons. Samples were obtained from the University of Texas MD Anderson Cancer Center and “Regina Elena” National Cancer Institute, Rome, Italy. All diagnoses were confirmed by genetic testing. Polyps were collected at the time of endoscopic surveillance and tumors were collected at the time of surgical resection. The data were analyzed from October 2016 to November 2017. MAIN OUTCOMES AND MEASURES: Assessment of the immune profile, mutational signature, mutational and neoantigen rate, and pathway enrichment analysis of neoantigens in LS premalignant lesions and their comparison with FAP premalignant lesions, LS carcinoma, and sporadic colorectal cancers from TCGA. RESULTS: The analysis was performed in a total of 28 polyps (26 tubular adenomas and 2 hyperplastic polyps) and 3 early-stage LS colorectal tumors from 24 patients (15 [62%] female; mean [SD] age, 48.12 [15.38] years) diagnosed with FAP (n = 10) and LS (n = 14). Overall, LS polyps presented with low mutational and neoantigen rates but displayed a striking immune activation profile characterized by CD4 T cells, proinflammatory (tumor necrosis factor, interleukin 12) and checkpoint molecules (LAG3 [lymphocyte activation gene 3] and PD-L1 [programmed cell death 1 ligand 1]). This immune profile was independent of mutational rate, neoantigen formation, and MMR status. In addition, we identified a small subset of LS polyps with high mutational and neoantigen rates that were comparable to hypermutant tumors and displayed additional checkpoint (CTLA4 [cytotoxic T-lymphocyte–associated protein 4]) and neoantigens involved in DNA damage response (ATM and BRCA1 signaling). CONCLUSIONS AND RELEVANCE: These findings challenge the canonical model, based on the observations made in carcinomas, that emphasizes a dependency of immune activation on the acquisition of high levels of mutations and neoantigens, thus opening the door to the implementation of immune checkpoint inhibitors and vaccines for cancer prevention in LS.

Because of the low incidence of nongastrointestinal stromal tumor (non-GIST) spindle cell sarcomas of the colon or rectum, the clinical behavior and ideal surgical treatment of these tumors and patient outcomes are poorly defined. The purpose of this study was to characterize these tumors and to determine the best surgical approach. We identified 1056 patients with non-GIST spindle cell sarcomas of the colon or rectum (1998–2010) in the National Cancer Database and collected data for each patient that included patient and tumor characteristics, tumor site (colon vsrectum), surgery type, and outcomes. The median overall survival was significantly longer in patients with rectal tumors than in those with colon tumors (P< 0.01). Patients with colon tumors who underwent anatomic surgical resection showed a trend toward longer median survival than those with no surgical treatment [hazard ratio (HR), 1.94; P= 0.09] or who underwent local excision (HR, 1.74; P= 0.09). Patients with rectal tumors did not benefit from anatomic surgical resection, but there was a trend favoring local excision (HR, 0.55; P= 0.06). Local sphincter-sparing procedures should be considered for rectal non-GIST tumors whenever technically feasible.

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The aim of the present study was to quantitatively diagnose and monitor the therapy response of hepatic ischemia–reperfusion injury (IRI) with the use of targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated, and the binding of intracellular adhesion molecule 1 (ICAM‐1) antibodies to MBs was observed. To establish a quantitative method based on targeted USimaging, contrast‐enhanced USwas applied for IRIrats. After andrographolide treatment, the IRIrats were subjected to the quantitative targeted USimaging for a therapeutic effect. Effective binding of ICAM‐1 antibodies to MBs was observed. According to the quantitative targeted USimaging, the ICAM‐1 normalized intensity difference (NID) in the IRIrats (38.74 ± 15.08%) was significantly higher than that in the control rats (10.08 ± 2.52%, p=0.048). Further, different degrees of IRI(mild IRI, moderate to severe IRI) were distinguished by the use of the NID(37.14 ± 2.14%, 22.34 ± 1.08%, p=0.002). Analysis of mRNAexpression demonstrated the accuracy of analyzing the NIDby using quantitative targeted USimaging (R2 = 0.7434, p< 0.001). Andrographolide treatment resulted in an obviously weakened NIDof ICAM‐1 (17.7 ± 4.8% vs 34.2 ± 6.6%, p< 0.001). The study showed the potential of the quantitative targeted USimaging method for the diagnosis and therapeutic monitoring of IRI. A quantitative ultrasound imaging method based on intracellular adhesion molecule 1 targeting can diagnose different degrees of hepatic ischemia–reperfusion injury and monitor anti‐inflammatory effects after andrographolide treatment.

Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma (GBM) progression, and many fusion genes are strong driver mutations in neoplasia and are involved in tumorigenesis. However, the ability of fusion genes to be transduced by exosomes is unknown. We characterized exosomes from GBM cells harbouring and not harbouring PTPRZ1–MET fusion (ZM fusion). We also determined the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic secretions and showed that ZM exosomes are internalized by the recipient cells. In addition, we studied the effect of ZM exosome-mediated intercellular communication in the GBM microenvironment. MET proto-oncogene expression was higher in ZM exosomes. Moreover, phosphorylated MET was detected only in ZM exosomes and not in exosomes released by non-ZM fusion GBM cells. ZM exosomes transferred to non-ZM fusion GBM cells and normal human astrocytes altered gene expression and induced epithelial–mesenchymal transition. The uptake of ZM exosomes also induced an exosome-dependent phenotype defined by GBM cell migration and invasion, neurosphere growth and angiogenesis. In addition, ZM exosomes conferred temozolomide resistance to the GBM cells, and exosome-derived ZM fusion network proteins targeted multiple pro-oncogenic effectors in recipient cells within the GBM microenvironment. Our findings show that exosomes mediate the aggressive character of GBM and demonstrate the role of ZM fusion in the exacerbation of this effect. These findings have possible implications for the foundation of gene fusion-based therapy for managing GBM.

We designed a novel haploidentical hematopoietic stem cell transplantation (haplo-HSCT) system using idarubicin (IDA) intensified conditioning regimens and combination of antithymocyte globulin and basiliximab for GvHD prophylaxis. The outcomes of 110 high-risk acute leukemia patients undergoing haplo-HSCT were compared with 69 contemporaneous high-risk patients receiving HLA-matched sibling transplantation using uniform IDA-intensified regimens. The relapse incidence of haplo-HSCT was 23.4%, and 3-year overall survival (OS) and disease-free survival (DFS) achieved 62.9%, 59.1%, respectively. The cumulative incidences of II–IV and III–IV aGvHD were 28.6 and 14.3%, while limited and extensive cGvHD were 19.4, 13.8%. All these results were equivalent to those of concurrent identical sibling transplantation. Three-year OS and DFS for patients in advance stage reached 48.5, 47.3%. Furthermore, the relapse, 3-year OS of positive minimal residual disease (MRD) patients did not differ from negative MRD patients (18.9% vs 11.5%, 63.6% vs 69.6%), indicating our intensified haplo-HSCT technique could circumvent the dismal prognosis of MRD. These data provide reinforcing evidence that our haplo-HSCT system could dramatically improve the survival of high-risk acute leukemia with low relapse and acceptable transplantation-related mortality, and might be a promising therapeutic option for high-risk patients.

Significant advances in systemic chemotherapy and surgical techniques have allowed a subset of patients with stage IV colorectal cancer to be suitable candidates for multimodality therapy with curative intent. Care of these patients requires multidisciplinary coordination, close monitoring of disease response, and individualized treatment plan. This review will discuss considerations for treatment planning and sequencing in patients with symptomatic and asymptomatic primary colon cancer in the setting of potentially resectable liver metastases.

Neuroimaging studies of autism spectrum disorder (ASD) have been predominantly unimodal. While many fMRI studies have reported atypical activity patterns for diverse tasks, the MEG literature in ASD remains comparatively small. Our group recently reported atypically increased event-related theta power in individuals with ASD during lexicosemantic processing. The current multimodal study examined the relationship between fMRI BOLD signal and anatomically-constrained MEG (aMEG) theta power. Thirty-three adolescents with ASD and 23 typically developing (TD) peers took part in both fMRI and MEG scans, during which they distinguished between standard words (SW), animal words (AW), and pseudowords (PW). Regions-of-interest (ROIs) were derived based on task effects detected in BOLD signal and aMEG theta power. BOLD signal and theta power were extracted for each ROI and word condition. Compared to TD participants, increased theta power in the ASD group was found across several time windows and regions including left fusiform and inferior frontal, as well as right angular and anterior cingulate gyri, whereas BOLD signal was significantly increased in the ASD group only in right anterior cingulate gyrus. No significant correlations were observed between BOLD signal and theta power. Findings suggest that the common interpretation of increases in BOLD signal and theta power as ‘activation’ require careful differentiation, as these reflect largely distinct aspects of regional brain activity. Some group differences in dynamic neural processing detected with aMEG that are likely relevant for lexical processing may be obscured by the hemodynamic signal source and low temporal resolution of fMRI.

The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain.

COREX is an industrially and commercially proven smelting reduction process. The shaft furnace (SF) for the pre-reduction of iron ore is one of the two major reactors of COREX. As one of the industrial systems using screw feeders, the burden descending behaviour in SF can be directly affected by the bottom structure such as the design of screw and associated charging container. In this work, a three-dimensional actual size model of COREX-3000 SF is established by means of the discrete element method. The effect of bottom structure, for example, the guiding cone and the design of screw, on solid flow is investigated. The results show that burdens are mainly drawn down from the first flight of the screw in the reference case, while the slow-moving particles located above the end of the screw. Placing a guiding cone and reducing the flight diameter of screw have a benefit for restraining the descending velocities in the central area of the SF and help to obtain a uniform flow pattern. An optimised case is also proposed. In the optimised case, a relatively uniform solid flow profile can be obtained and the uniformity of descending velocity along the radius is improved greatly. The findings of this work should be useful for the design, control and optimisation of the SF operation.

Soft x-ray lasing at 18.9 nm and 20.3 nm in nickel-like molybdenum and niobium ions has been demonstrated using two 200 ps laser pulses with ~0.2TW laser power at [MATH] from XingGuang II laser facility. A comparison has been made of performance of the neon-like chromium soft x-ray lasing at 28.5nm driven by a double 900 ps pulse at 6 TW/cm2, compare to that driven by a double 200 ps pulse at similar irradiance. The 900 ps pulse duration was found to be able to provide stronger emission and narrower divergence of neon-like chromium soft x-ray lasing.

COREX is an industrially and commercially proven smelting reduction process. The shaft furnace (SF) for the direct reduction of iron ore is one of the two major reactors of COREX. In the new design of COREX-3000 SF in Baosteel, China, a new technique called areal gas distribution (AGD) has been adopted. With the installation of two AGD beams, the cross-sectional area varies in a complicated manner, which will affect the burden descending behaviour. This work uses a slot model to investigate the solid flow behaviour in the SF by discrete element method. The applicability of the discrete element method model is validated. The results confirm that the flow profile in SF with AGD evolves from a flat to wave and finally to W profile as the solids descend. A triangle shaped free area is observed under the AGD beam, which is the main channel for gas flow into the shaft centre. Increasing the discharging rate has an effect of decreasing the quasi-stagnant zone size, but does not affect the macroscopic motion of particles and flow pattern above the bustle. The cross-section of AGD channel increase with the increase in the discharging rate. Under the asymmetric condition, the solid flow pattern is asymmetric. The influence of AGD on macro- and microscope properties of solid flow in SF is also evaluated. This investigation reveals that AGD beams affect the particle uniform descending in bustle zone and increase the complexity of normal force distribution.

Delayed adjuvant chemotherapy (AC) for patients with stage III colon cancer adversely impacts outcomes and is the focus of a National Quality Forum (NQF) quality metric. One in 5 patients initiates AC within the NQF-endorsed interval but does not derive the full benefit.

Purpose:Mismatch repair-deficient (MMRD) colorectal cancer (CRC) and endometrial cancer (EC) may be suggestive of Lynch syndrome (LS). LS can be confirmed only by positive germ-line testing. It is unclear if individuals with MMRD tumors but no identifiable cause (MMRD+/germ-line-) have LS. Because LS is hereditary, individuals with LS are expected to have family histories of LS-related tumors. Our study compared the family histories of MMRD+/germ-line- CRC and/or EC patients with LS CRC and/or EC patients.Methods:A total of 253 individuals with an MMRD CRC or EC from one institution were included for analysis in one of four groups: LS; MMRD+/germ-line-; MMRD tumor with variant of uncertain significance (MMRD+/VUS); and sporadic MSI-H (MMRD tumor with MLH1 promoter hypermethylation or BRAF mutation). Family histories were analyzed utilizing MMRpro and PREMM1,2,6. Kruskal–Wallis tests were used to compare family history scores.Results:MMRD+/germ-line- individuals had significantly lower median family history scores (MMRpro = 8.1, PREMM1,2,6= 7.3) than did LS individuals (MMRpro = 89.8, PREMM1,2,6= 26.1, P < 0.0001).Conclusion:MMRD+/germ-line- individuals have less suggestive family histories of LS than individuals with LS. These results imply that MMRD+/germ-line- individuals may not all have LS. This finding highlights the need to determine other causes of MMRD tumors so that these patients and their families can be accurately counseled regarding screening and management.Genet Med 17 6, 476–484.

IMPORTANCE: Colon cancer is increasing among adults younger than 50 years. However, the prognosis of young-onset colon cancer remains poorly defined given significant age-related demographic, disease, and treatment differences. OBJECTIVE: To define stage-specific treatments and prognosis of colon cancer diagnosed in young adults (ages 18-49 years) vs older adults (ages 65-75 years) outside of the clinical trial setting while accounting for real-world age-related variations in patient, tumor, and treatment factors. DESIGN, SETTING, AND PARTICIPANTS: A nationwide cohort study was conducted among US hospitals accredited by the American College of Surgeons Commission on Cancer. Participants were 13 102 patients diagnosed as having young-onset colon adenocarcinoma aged 18 to 49 years and 37 007 patients diagnosed as having later-onset colon adenocarcinoma aged 65 to 75 years treated between January 1, 2003, and December 31, 2005, and reported to the National Cancer Data Base. EXPOSURES: Patients who underwent surgical resection and postoperative systemic chemotherapy of curative intent. MAIN OUTCOMES AND MEASURES: The primary end point was stage-specific relative survival, an objective measure of survival among patients with cancer, adjusting for baseline mortality rates and independent of the data on cause of death. The secondary end point was stage-specific likelihood of receiving postoperative systemic chemotherapy. RESULTS: Most young-onset colon cancer was initially seen at advanced stages (61.8% had stage III or IV). After adjusting for patient-related and tumor-related factors, young patients were more likely to receive systemic chemotherapy, particularly multiagent regimens, at all stages relative to those with later-onset disease. These odds ratios were 2.88 (95% CI, 2.21-3.77) for stage I, 3.93 (95% CI, 3.58-4.31) for stage II, 2.42 (95% CI, 2.18-2.68) for stage III, and 2.74 (95% CI, 2.44-3.07) for stage IV. The significantly more intense treatments received by younger patients were unmatched by any survival gain, which was nil for stage II (relative risk, 0.90; 95% CI, 0.69-1.17) and marginal for stage III (relative risk, 0.89; 95% CI, 0.81-0.97) and stage IV (relative risk, 0.84; 95% CI, 0.79-0.90). CONCLUSIONS AND RELEVANCE: Young adults with colon cancer received significantly more postoperative systemic chemotherapy at all stages, but they experienced only minimal gain in adjusted survival compared with their older counterparts who received less treatment. This mismatch suggests that attention should be given to long-term cancer survivorship in young adults with colon cancer because they likely face survivorship needs that are distinct from those of their older counterparts.

The present investigation was aimed at elucidating solid particle behaviour in a new design COREX shaft furnace using a new technique called areal gas distribution (AGD). The measurement of solid flow profile was performed with a semi-cylindrical model. To guarantee similarity of conditions, a modified Froude number was taken into consideration in the physical model constructed. The solid flow characteristics in this new furnace with different blast volumes were analysed, and the effect of discharge rate as well as abnormal conditions on solid flow behaviour have also been investigated. The work reveals that solid flow profile in the shaft furnace model progresses through a Flat?Wave?W shape profile as the burden descends. Blast volume has little influence on solid particle behaviour. However, increasing the discharge rate has an effect of decreasing the quasi-stagnant zone size and with the increasing discharge rate, the cross-section of AGD channel increases. For asymmetric flow, particles descend from the top and move to the discharging outlet and a very big stagnant zone is formed on the opposite side of the discharging outlet.

IMPORTANCE: With the advent of effective modern chemotherapeutic and biologic agents, primary tumor resection for patients with stage IV colorectal cancer (CRC) may not be routinely necessary. OBJECTIVE: To evaluate the secular patterns of primary tumor resection use in stage IV CRC in the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results CRC registry. Demographic and clinical factors were compared for 64 157 patients diagnosed with stage IV colon or rectal cancer from January 1, 1988, through December 31, 2010, who had undergone primary tumor resection and those who had not. Rates of primary tumor resection and median relative survival were calculated for each year. Joinpoint regression analysis was used to determine when a significant change in trend in the primary tumor resection rate had occurred. Logistic regression analysis was used to assess factors associated with primary tumor resection. MAIN OUTCOMES AND MEASURES: Difference in primary tumor resection rates over time. RESULTS: Of the 64 157 patients with stage IV CRC, 43 273 (67.4%) had undergone primary tumor resection. The annual rate of primary tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 (P &lt; .001), and a significant annual percentage change occurred between 1998-2001 and 2001-2010 (–0.41% vs –2.39%; P &lt; .001). Factors associated with primary tumor resection were age younger than 50 years, female sex, being married, higher tumor grade, and presence of colon tumors. Median relative survival rate improved from 8.6% in 1988 to 17.8% in 2009 (P &lt; .001); the annual percentage change was 2.18% in 1988-2001 and 5.43% in 1996-2009 (P &lt; .001). CONCLUSIONS AND RELEVANCE: The majority of patients with stage IV CRC had undergone primary tumor resection but, beginning in 2001, a trend toward fewer primary tumor resections was seen. Despite the decreasing primary tumor resection rate, patient survival rates improved. However, primary tumor resection may still be overused, and current treatment practices lag behind evidence-based treatment guidelines.

IMPORTANCE: The overall incidence of colorectal cancer (CRC) has been decreasing since 1998 but there has been an apparent increase in the incidence of CRC in young adults. OBJECTIVE: To evaluate age-related disparities in secular trends in CRC incidence in the United States. DESIGN, SETTING, AND PATIENTS: A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) CRC registry. Age at diagnosis was analyzed in 15-year intervals starting at the age of 20 years. SEER*Stat was used to obtain the annual cancer incidence rates, annual percentage change, and corresponding P values for the secular trends. Data were obtained from the National Cancer Institute’s SEER registry for all patients diagnosed as having colon or rectal cancer from January 1, 1975, through December 31, 2010 (N = 393 241). MAIN OUTCOME AND MEASURE: Difference in CRC incidence by age. RESULTS: The overall age-adjusted CRC incidence rate decreased by 0.92% (95% CI, −1.14 to −0.70) between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed for young adults. For patients 20 to 34 years, the incidence rates of localized, regional, and distant colon and rectal cancers have increased. An increasing incidence rate was also observed for patients with rectal cancer aged 35 to 49 years. Based on current trends, in 2030, the incidence rates for colon and rectal cancers will increase by 90.0% and 124.2%, respectively, for patients 20 to 34 years and by 27.7% and 46.0%, respectively, for patients 35 to 49 years. CONCLUSIONS AND RELEVANCE: There has been a significant increase in the incidence of CRC diagnosed in young adults, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies.

For patients with residual or recurrent squamous-cell carcinoma of the anus after primary chemoradiotherapy, the standard treatment is surgical salvage. Patients with unresectable or borderline unresectable disease have poor outcomes, thus adjunctive treatments should be explored.

In the United States, colorectal cancer (CRC) is the third most common and second most lethal cancer. More than one-tenth of CRC cases (11% of colon cancers and 18% of rectal cancers) have a young onset (ie, occurring in individuals younger than 50 years). The CRC incidence and mortality rates are decreasing among all age groups older than 50 years, yet increasing in younger individuals for whom screening use is limited and key symptoms may go unrecognized. Familial syndromes account for approximately 20% of young-onset CRCs, and the remainder are typically microsatellite stable cancers, which are more commonly diploid than similar tumors in older individuals. Young-onset CRCs are more likely to occur in the distal colon or rectum, be poorly differentiated, have mucinous and signet ring features, and present at advanced stages. Yet, stage-specific survival in patients with young-onset CRC is comparable to that of patients with later-onset cancer. Primary care physicians have an important opportunity to identify high-risk young individuals for screening and to promptly evaluate CRC symptoms. Risk modification, targeted screening, and prophylactic surgery may benefit individuals with a predisposing hereditary syndrome or condition (eg, inflammatory bowel disease) or a family history of CRC or advanced adenomatous polyps. When apparently average-risk young adults present with CRC-like symptoms (eg, unexplained persistent rectal bleeding, anemia, and abdominal pain), endoscopic work-ups can expedite diagnosis. Early screening in high-risk individuals and thorough diagnostic work-ups in symptomatic young adults may improve young-onset CRC trends.

IMPORTANCE The circumferential resection margin is the primary determinant of local recurrence and a major factor in survival in rectal cancer. Neither chemotherapy nor chemoradiation compensates for a margin positive for cancer. OBJECTIVE To identify treatment-related factors associated with hospital margin-positive resection and to develop a tool that could be used by individual hospitals to assess their outcomes based on their unique mix of patient and tumor characteristics. DESIGN Retrospective review of the National Cancer Data Base, 1998-2007. SETTINGS Community and academic/research hospitals. PARTICIPANTS Individuals with histologically confirmed localized rectal/rectosigmoid adenocarcinoma. EXPOSURE All individuals underwent radical resection for rectal cancer with or without neoadjuvant therapy. MAIN OUTCOMES AND MEASURES Rate of margin positivity determined and adjusted for patient- and tumor-related factors to calculate expected margin positivity per hospital. An observed to expected ratio was calculated based on patient- and tumor-related factors to identify treatment-associated variation. RESULTS The overall margin-positive resection rate was 5.2%. Patients with margins positive for cancer were more likely to be older, male, and African American; not have private insurance; and have their cancer diagnosed later in the study period. Associated tumor-related factors include rectal location, higher American Joint Committee on Cancer stage, signet/mucinous histology, and poor/undifferentiated grade. Among hospitals that were significantly low outliers, 47% were comprehensive community hospitals, and 43.9% were academic/research hospitals; of those that were significantly high outliers, 52.3% were comprehensive community hospitals, and 17.8% were academic/research hospitals. High-volume centers made up 80% of significantly low outlier hospitals and 17% of significantly high outlier hospitals. The rates of chemotherapy and radiation were similar, but low outlier hospitals gave more neoadjuvant radiation (26.3% vs 17%). CONCLUSIONS AND RELEVANCE After adjustment for patient- and tumor-related factors, we identified both low and high outlier hospitals for margin positivity at resection, as well as potentially modifiable risk factors. The nomogram created in this model allows for the evaluation of observed and expected event rates for individual hospitals, providing a hospital self-assessment tool for identifying targets for improvement.

The generation of terahertz radiation from an ensemble of aligned air molecules in intense two-color laser fields has been investigated. Our experiments show that terahertz radiation yields are strongly modulated by the alignment of nitrogen and oxygen molecules. We explain this phenomenon in the context of the plasma current model combined with alignment-dependent ionization, in which nitrogen molecules aligned parallel to the laser field yield more ionization and plasma currents, resulting in enhanced terahertz radiation. Our measurements also provide the ratio of the ensemble-averaged ionization rates of nitrogen molecules aligned parallel versus orthogonal to the laser field. [ABSTRACT FROM AUTHOR]