The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study.

BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

Adaptive irrigation management by Balinese farmers reduces greenhouse gas emissions and increases rice yields.

The potential for changes in water management regimes to reduce greenhouse gases (GHG) in rice paddies has recently become a major topic of research in Asia, with implications for top-down versus bottom-up management strategies. Flooded rice paddies are a major source of anthropogenic GHG emissions and are responsible for approximately 11% of global anthropogenic methane (CH4) emissions. However, rice is also the most important food crop for people in low- and lower-middle-income countries. While CH4 emissions can be reduced by lessening the time the plants are submerged, this can trigger increased emissions of nitrous oxide (N2O), a more potent GHG. Mitigation options for CH4 and N2O are different, and minimizing one gas may increase the emission of the other. Accurate measurement of these gas emissions in rice paddies is difficult, and the results are controversial. We analysed these trade-offs using continuous high-precision measurements in a closed chamber in 2018-2020. Based on the results, we tested a bottom-up adaptive irrigation regime that improves nitrogen uptake by rice plants while reducing combined GHG emissions and nitrogen runoff from paddies to reefs in agricultural drainages. In 2023, we undertook a follow-up study in which farmers obtained higher rice yields with adaptive intermittent irrigation compared to uniformly flooded fields. These results use the polycentric, self-governing capacity of Balinese subaks for continuous adaptation. This article is part of the theme issue 'Climate change adaptation needs a science of culture'.

Vascular abnormalities - a true cause of pulsatile tinnitus?

OBJECTIVE: Pulsatile tinnitus can be a symptom of vascular pathology. However, many of these pathologies present as incidental findings on scanning for unrelated symptoms. This study investigated whether the pathologies attributed to pulsatile tinnitus could instead be considered incidental findings. METHODS: This retrospective study evaluated imaging results of 272 pulsatile tinnitus cases for clinically relevant pathologies, and examined correlations between the site of symptoms and the imaging findings. RESULTS: Of 272 patients, 238 (88 per cent) had normal scans, 17 (6 per cent) had clinically insignificant incidental findings, and 18 (7 per cent) had findings requiring further investigation or intervention; regarding these latter 18 patients, findings for 8 patients (42 per cent) did not correlate with the symptomatic side. The rates of intracranial aneurysm and arteriovenous malformation in the pulsatile tinnitus group were comparable to those in normal populations. CONCLUSION: The comparable rates of vascular abnormalities within the symptomatic pulsatile tinnitus group, plus clinically relevant findings contralateral to symptoms, suggest that vascular pathologies could be incidental findings rather than causes of pulsatile tinnitus. Evaluation is recommended of the effectiveness of the new National Institute for Health and Care Excellence guidelines for pulsatile tinnitus investigation.

The impact of robotics in liver surgery: A worldwide systematic review and short-term outcomes meta-analysis on 2,728 cases.

BACKGROUND: The dissemination of robotic liver surgery is slow-paced and must face the obstacle of demonstrating advantages over open and laparoscopic (LLS) approaches. Our objective was to show the current position of robotic liver surgery (RLS) worldwide and to identify if improved short-term outcomes are observed, including secondary meta-analyses for type of resection, etiology, and cost analysis. METHODS: A PRISMA-based systematic review was performed to identify manuscripts comparing RLS vs open or LLS approaches. Quality analysis was performed using the Newcatle-Ottawa score. Statistical analysis was performed after heterogeneity test and fixed- or random-effect models were chosen accordingly. RESULTS: After removing duplications, 2728 RLS cases were identified from the final set of 150 manuscripts. More than 75% of the cases have been performed on malignancies. Meta-analysis from the 38 comparative reports showed that RLS may offer improved short-term outcomes compared to open procedures in most of the variables screened. Compared to LLS, some advantages may be observed in favour of RLS for major resections in terms of operative time, hospital stay and rate of complications. Cost analyses showed an increased cost per procedure of around US$5000. CONCLUSIONS: The advantages of RLS still need to be demonstrated although early results are promising. Advantages vs open approach are demonstrated. Compared to laparoscopic surgery, minor perioperative advantages may be observed for major resections although cost analyses are still unfavorable to the robotic approach.

The impact of workload on hand hygiene compliance: Is 100% compliance achievable?

Hand hygiene compliance decreased significantly when opportunities exceeded 30 per hour. At higher workloads, the number of healthcare worker types involved and the proportion of hand hygiene opportunities for which physicians and other healthcare workers were responsible increased. Thus, care complexity and risk to patients may both increase with workload.

An observational clinical study of the influence of phacoemulsification on choroidal neovascular membrane activity in age related macular degeneration.

BACKGROUND: Thousands of phacoemulsification surgeries are performed on eyes with age-related macular degeneration (AMD) complicated by choroidal neovascular membrane (CNV) in the United Kingdom each year. As populations age this number is expected to rise. Controversy over phacoemulsification's influence on CNV activity limits the information which clinicians and these patients use to decide on surgery. This observational study aims to resolve this controversy by reporting on intravitreal injection (IVI) frequency as a pragmatic marker of CNV activity in a large cohort. METHODS: A cohort of eyes with AMD complicated by CNV (n = 327) that underwent cataract surgery at a single tertiary centre from 2014 to 2019 were identified. These cases were matched by interval since CNV diagnosis at a specified 'time zero' within the follow-up of pseudophakic eyes with AMD (n = 327). Data concerning demographics, visual acuity (VA) and intravitreal injection frequency before and after 'time zero'/phacoemulsification were collected. RESULTS: Following 'time zero'/phacoemulsification' the mean reduction in annual IVI frequency was 0.6 injections/year (95% CI 0.4,0.9) and 0.4 injections/year (95% CI 0.1,0.7) in the comparison and phacoemulsification cohorts respectively. The mean VA gain 12 months after phacoemulsification in the intervention cohort was 11.3 (95% CI 9.2,13.4) early treatment of diabetic retinopathy study (ETDRS) letters, with 214 eyes (65.4%) having gained ≥5 ETDRS letters after surgery. CONCLUSIONS: Phacoemulsification has no clinically significant impact on the activity of pre-existent CNV secondary to AMD. Phacoemulsification should be offered to patients with AMD and cataract that limits vision, regardless of CNV activity.

Exposure to tick-borne encephalitis virus among nature management workers in the Netherlands.

Tick-borne encephalitis virus (TBEV) has only recently been detected in the Netherlands. With still few autochthonous tick-borne encephalitis (TBE) patients, human exposure to TBEV is expected to be very low among the general population. We aimed to assess the exposure to TBEV among persons with an occupationally high risk of tick bites in the Netherlands. In our cross-sectional serological survey, employees and volunteers of nature management organizations provided a single blood sample and completed an online questionnaire in 2017. The sera were screened in the anti-TBEV IgG Enzyme-Linked Immunosorbent Assay (ELISA), after which a TBEV-specific virus neutralization test (VNT) was applied to confirm positive ELISA outcomes. Ten sera tested positive for IgG antibodies in the TBEV ELISA, among 556 participants who did not report vaccination against TBEV. Through confirmation in VNT, TBEV-specific IgG antibodies were detected among 0.5% (3/556, 95%CI 0.1%-1.6%). During the five years prior to the questionnaire, 87% reported tick bites. Half of the participants considered that most of their tick bites (75% to 100%) had been acquired while being at work. A very low seroprevalence of TBEV exposure was observed among these nature management workers, even though they report a six times higher exposure to tick bites, compared to our general population. Nonetheless, the emergence of TBEV in the Netherlands reaffirms the need for education and preventative measures against tick bites and tick-borne diseases.

Modelling Singapore COVID-19 pandemic with a SEIR multiplex network model.

In this paper, we have implemented a large-scale agent-based model to study the outbreak of coronavirus infectious diseases (COVID-19) in Singapore, taking into account complex human interaction pattern. In particular, the concept of multiplex network is utilized to differentiate between social interactions that happen in households and workplaces. In addition, weak interactions among crowds, transient interactions within social gatherings, and dense human contact between foreign workers in dormitories are also taken into consideration. Such a categorization in terms of a multiplex of social network connections together with the Susceptible-Exposed-Infectious-Removed (SEIR) epidemic model have enabled a more precise study of the feasibility and efficacy of control measures such as social distancing, work from home, and lockdown, at different moments and stages of the pandemics. Using this model, we study an epidemic outbreak that occurs within densely populated residential areas in Singapore. Our simulations show that residents in densely populated areas could be infected easily, even though they constitute a very small fraction of the whole population. Once infection begins in these areas, disease spreading is uncontrollable if appropriate control measures are not implemented.

Oral ß-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source.

Importance: Oral ß-lactam antibiotics are traditionally not recommended to treat Enterobacterales bacteremia because of concerns over subtherapeutic serum concentrations, but there is a lack of outcomes data, specifically after initial treatment with parenteral antibiotics. Given the limited data and increasing limitations of fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX), oral ß-lactam antibiotics may be a valuable additional treatment option. Objective: To compare definitive therapy with oral ß-lactam antibiotics vs fluoroquinolones or TMP-SMX for Enterobacterales bacteremia from a suspected urine source. Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 2007, to September 30, 2015, at 114 Veterans Affairs hospitals among 4089 adults with Escherichia coli, Klebsiella spp, or Proteus spp bacteremia and matching urine culture results. Additional inclusion criteria were receipt of active parenteral antibiotic(s) followed by conversion to an oral antibiotic. Exclusion criteria were previous Enterobacterales bacteremia, urologic abscess, or chronic prostatitis. Data were analyzed from April 15, 2019, to July 26, 2020. Exposures: Conversion of therapy to an oral ß-lactam antibiotic vs fluoroquinolones or TMP-SMX after 1 to 5 days of parenteral antibiotics. Main Outcomes and Measures: The main outcome was a composite of either 30-day all-cause mortality or 30-day recurrent bacteremia. Propensity-based overlap weights were used to adjust for differences between groups. Log binomial regression models were used to estimate adjusted relative risks (aRRs) and adjusted risk differences (aRDs). Results: Of the 4089 eligible patients (3731 men [91.2%]; median age, 71 years [interquartile range, 63-81 years]), 955 received an oral ß-lactam antibiotic, and 3134 received fluoroquinolones or TMP-SMX. The primary outcome occurred for 42 patients (4.4%) who received ß-lactam antibiotics and 94 patients (3.0%) who received fluoroquinolones or TMP-SMX (aRD, 0.99% [95% CI, -0.42% to 2.40%]; aRR, 1.31 [95% CI, 0.87-1.95]). Mortality rates were 3.0% (n = 29) for patients receiving ß-lactam antibiotics vs 2.6% (n = 82) for those receiving fluoroquinolones or TMP-SMX (aRD, 0.06% [95% CI, -1.13% to 1.26%]; aRR, 1.02 [95% CI, 0.67-1.56]). Recurrent bacteremia rates were 1.5% (n = 14) among those receiving ß-lactam antibiotics vs 0.4% (n = 12) among those receiving fluoroquinolones or TMP-SMX (aRD, 1.03% [95% CI, 0.24%-1.82%]; aRR, 3.43 [95% CI, 0.42-27.90]). Conclusions and Relevance: In this cohort study of adults with E coli, Klebsiella spp, or Proteus spp bacteremia from a suspected urine source, the relative risk of recurrent bacteremia was not significantly higher with ß-lactam antibiotics compared with fluoroquinolones or TMP-SMX, and the absolute risk and risk difference were small (ie, <3%). No significant difference in mortality was observed. Oral ß-lactam antibiotics may be a reasonable step-down treatment option, primarily when alternative options are limited by resistance or adverse effects. Further study is needed because statistical power was limited owing to a low number of recurrent bacteremia events.

The ELFIN Mission.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with <0.3 nT/sqrt(Hz) noise at 1 Hz. The spinning satellites (Tspin ∼ 3 s) are equipped with magnetorquers (air coils) that permit spin-up or -down and reorientation maneuvers. Using those, the spin axis is placed normal to the orbit plane (nominally), allowing full pitch-angle resolution twice per spin. An energetic particle detector for ions (EPDI) measures 250 keV - 5 MeV ions, addressing secondary science. Funded initially by CalSpace and the University Nanosat Program, ELFIN was selected for flight with joint support from NSF and NASA between 2014 and 2018 and launched by the ELaNa XVIII program on a Delta II rocket (with IceSatII as the primary). Mission operations are currently funded by NASA. Working under experienced UCLA mentors, with advice from The Aerospace Corporation and NASA personnel, more than 250 undergraduates have matured the ELFIN implementation strategy; developed the instruments, satellite, and ground systems and operate the two satellites. ELFIN's already high potential for cutting-edge science return is compounded by concurrent equatorial Heliophysics missions (THEMIS, Arase, Van Allen Probes, MMS) and ground stations. ELFIN's integrated data analysis approach, rapid dissemination strategies via the SPace Environment Data Analysis System (SPEDAS), and data coordination with the Heliophysics/Geospace System Observatory (H/GSO) optimize science yield, enabling the widest community benefits. Several storm-time events have already been captured and are presented herein to demonstrate ELFIN's data analysis methods and potential. These form the basis of on-going studies to resolve the primary mission science objective. Broad energy precipitation events, precipitation bands, and microbursts, clearly seen both at dawn and dusk, extend from tens of keV to >1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma.

INTRODUCTION: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. MATERIALS AND METHODS: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. RESULTS: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. CONCLUSION: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.

Distributions of discrete spherical particles with a constant susceptibility can lead to echo time dependent phase shifts which deviate from theories.

PURPOSE: When an object contains a distribution of discrete magnetic inclusions with a constant susceptibility, the MRI signal inside the object may no longer be determined analytically by assuming that the object is uniform or magnetic inclusions are completely random. Through simulations and experiments with spherical particles inside cylinders, this work is to study the signal behavior in the static dephasing regime. METHODS: MRI complex images of long cylinders containing spherical particles with different arrangements were simulated and compared to similar experimental phantom data. All experiments were designed for the static dephasing regime so that diffusion was neglected. RESULTS: Several factors can lead to different phase shifts over echo time. These include numbers of particles per image voxel, particle arrangements, and Gibbs ringing effects. Purely random arrangements of particles in simulations can agree with a revised theoretical formula at short echo times, but quasi-random arrangements of particles do not agree with the theory. In addition, close to half of experimental results show deviations from the theory and the quasi-random arrangements of particles can explain those experimental results. Simulated R2' values are about the same for different cylinder orientations but increase when random particle arrangement is restricted toward lattice. Nonetheless, as expected, phase distributions outside and far away from each cylinder are independent of any factor affecting phase inside and behave as if they are from a cylinder with a uniform bulk susceptibility. CONCLUSION: Phase over echo time inside an object containing discrete spheres can be nonlinear and deviate from current theories in the static dephasing regime. Phase outside the object can be used to accurately determine its magnetic moment and bulk susceptibility without a priori knowledge of the spherical particle distribution inside the object. These results can be extended to the subcortical gray matter and suggest that in vivo susceptibility quantification will need to be re-thought.

Association between universal gloving and healthcare-associated infections: A systematic literature review and meta-analysis.

OBJECTIVE: Healthcare-associated infections (HAIs) are a significant burden on healthcare facilities. Universal gloving is a horizontal intervention to prevent transmission of pathogens that cause HAI. In this meta-analysis, we aimed to identify whether implementation of universal gloving is associated with decreased incidence of HAI in clinical settings. METHODS: A systematic literature search was conducted to find all relevant publications using search terms for universal gloving and HAIs. Pooled incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using random effects models. Heterogeneity was evaluated using the Woolf test and the I2 test. RESULTS: In total, 8 studies were included. These studies were moderately to substantially heterogeneous (I2 = 59%) and had varied results. Stratified analyses showed a nonsignificant association between universal gloving and incidence of methicillin-resistant Staphylococcus aureus (MRSA; pooled IRR, 0.94; 95% CI, 0.79-1.11) and vancomycin-resistant enterococci (VRE; pooled IRR, 0.94; 95% CI, 0.69-1.28). Studies that implemented universal gloving alone showed a significant association with decreased incidence of HAI (IRR, 0.77; 95% CI, 0.67-0.89), but studies implementing universal gloving as part of intervention bundles showed no significant association with incidence of HAI (IRR, 0.95; 95% CI, 0.86-1.05). CONCLUSIONS: Universal gloving may be associated with a small protective effect against HAI. Despite limited data, universal gloving may be considered in high-risk settings, such as pediatric intensive care units. Further research should be performed to determine the effects of universal gloving on a broader range of pathogens, including gram-negative pathogens.

Case report: electrical automated massage chair use can induce osteoporotic vertebral compression fracture.

This case report describes a case of an elderly woman diagnosed with acute osteoporotic vertebral compression fracture (OVCF) at thoracic spine after using an electrical automated massage chair (EAMC). Care should be taken when using an EAMC, especially by those with or at risk of developing osteoporosis. Osteoporotic vertebral compression fracture (OVCF) is a common problem among elderly population and presents a high burden to society. Osteoporotic fractures may occur after a minimal trauma of the vertebrae. Electrical automated massage chair (EAMC) is a device that uses a programmed algorithm to perform automated massage. The massage chair, a popular device among elderly with back pain, relies on friction and rhythmic tapping created by a motorized roller. However, research regarding the safety of this device is lacking, especially in the perspective of OVCF. We present a case of an elderly woman diagnosed with acute OVCF of the thoracic spine after using an EAMC. The patient had no risk factor for fragility fracture and experienced an abrupt onset of severe upper back pain while using EAMC. Imaging studies revealed an isolated acute compression fracture at T8 vertebra (AO classification type A1) while dual-energy X-Ray absorptiometry scan confirmed osteoporosis. The patient was treated with a plastic orthosis and oral medications for osteoporosis. After 6-months follow-up, the patient showed union of the fractured T8 vertebra and no remaining symptoms. This case highlights that OVCF can be induced by EAMC. Therefore, patients with or at risk for osteoporosis should be cautious while opting for deep tissue massage using EAMC.

A study of MRI gradient echo signals from discrete magnetic particles with considerations of several parameters in simulations.

Modeling MRI signal behaviors in the presence of discrete magnetic particles is important, as magnetic particles appear in nanoparticle labeled cells, contrast agents, and other biological forms of iron. Currently, many models that take into account the discrete particle nature in a system have been used to predict magnitude signal decays in the form of R2* or R2' from one single voxel. Little work has been done for predicting phase signals. In addition, most calculations of phase signals rely on the assumption that a system containing discrete particles behaves as a continuous medium. In this work, numerical simulations are used to investigate MRI magnitude and phase signals from discrete particles, without diffusion effects. Factors such as particle size, number density, susceptibility, volume fraction, particle arrangements for their randomness, and field of view have been considered in simulations. The results are compared to either a ground truth model, theoretical work based on continuous mediums, or previous literature. Suitable parameters used to model particles in several voxels that lead to acceptable magnetic field distributions around particle surfaces and accurate MR signals are identified. The phase values as a function of echo time from a central voxel filled by particles can be significantly different from those of a continuous cubic medium. However, a completely random distribution of particles can lead to an R2' value which agrees with the prediction from the static dephasing theory. A sphere with a radius of at least 4 grid points used in simulations is found to be acceptable to generate MR signals equivalent from a larger sphere. Increasing number of particles with a fixed volume fraction in simulations reduces the resulting variance in the phase behavior, and converges to almost the same phase value for different particle numbers at each echo time. The variance of phase values is also reduced when increasing the number of particles in a fixed voxel. These results indicate that MRI signals from voxels containing discrete particles, even with a sufficient number of particles per voxel, cannot be properly modeled by a continuous medium with an equivalent susceptibility value in the voxel.

Social Cooperation and Disharmony in Communities Mediated through Common Pool Resource Exploitation.

It was theorized that when a society exploits a shared resource, the system can undergo extreme phase transition from full cooperation in abiding by a social agreement, to full defection from it. This was shown to happen in an integrated society with complex social relationships. However, real-world agents tend to segregate into communities whose interactions contain features of the associated community structure. We found that such social segregation softens the abrupt extreme transition through the emergence of multiple intermediate phases composed of communities of cooperators and defectors. Phase transitions thus now occur through these intermediate phases which avert the instantaneous collapse of social cooperation within a society. While this is beneficial to society, it nonetheless costs society in two ways. First, the return to full cooperation from full defection at the phase transition is no longer immediate. Community linkages have rendered greater societal inertia such that the switch back is now typically stepwise rather than a single change. Second, there is a drastic increase in social disharmony within the society due to the greater tension in the relationship between segregated communities of defectors and cooperators. Intriguingly, these results on multiple phases with its associated phenomenon of social disharmony are found to characterize the level of cooperation within a society of Balinese farmers who exploit water for rice production.

TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication.

OBJECTIVE: We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. DESIGN: We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. RESULTS: We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. CONCLUSIONS: Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.