Two-Argument Activation Functions Learn Soft XOR Operations Like Cortical Neurons.

Neurons in the brain are complex machines with distinct functional compartments that interact nonlinearly. In contrast, neurons in artificial neural networks abstract away this complexity, typically down to a scalar activation function of a weighted sum of inputs. Here we emulate more biologically realistic neurons by learning canonical activation functions with two input arguments, analogous to basal and apical dendrites. We use a network-in-network architecture where each neuron is modeled as a multilayer perceptron with two inputs and a single output. This inner perceptron is shared by all units in the outer network. Remarkably, the resultant nonlinearities often produce soft XOR functions, consistent with recent experimental observations about interactions between inputs in human cortical neurons. When hyperparameters are optimized, networks with these nonlinearities learn faster and perform better than conventional ReLU nonlinearities with matched parameter counts, and they are more robust to natural and adversarial perturbations.

A Map-like Micro-Organization of Grid Cells in the Medial Entorhinal Cortex.

How the topography of neural circuits relates to their function remains unclear. Although topographic maps exist for sensory and motor variables, they are rarely observed for cognitive variables. Using calcium imaging during virtual navigation, we investigated the relationship between the anatomical organization and functional properties of grid cells, which represent a cognitive code for location during navigation. We found a substantial degree of grid cell micro-organization in mouse medial entorhinal cortex: grid cells and modules all clustered anatomically. Within a module, the layout of grid cells was a noisy two-dimensional lattice in which the anatomical distribution of grid cells largely matched their spatial tuning phases. This micro-arrangement of phases demonstrates the existence of a topographical map encoding a cognitive variable in rodents. It contributes to a foundation for evaluating circuit models of the grid cell network and is consistent with continuous attractor models as the mechanism of grid formation.

Correction: High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men.

[This corrects the article DOI: 10.1371/journal.pone.0172666.].

Higher and increased concentration of hs-CRP within normal range can predict the incidence of metabolic syndrome in healthy men.

AIMS: To determine whether hs-CRP level and interval change of hs-CRP could predict the development of metabolic abnormalities in healthy subjects in a longitudinal study. METHODS: A cohort of 3748 male who had normal hs-CRP level without evidence of any component of metabolic syndrome were studied. At each visit, hs-CRP level and metabolic abnormalities were measured. Interval change of hs-CRP for each subject was calculated. COX proportional hazard model and logistic regression analysis were used. RESULTS: Cumulative incidence and incidence density of metabolic syndrome were 3.96% and 7.17 per 1000 person-year, respectively. Cumulative incidence of metabolic syndrome was significantly increased according to hs-CRP tertile level. This significance remained after adjusting age, smoking, drinking, and exercise. Although the hazard ratio of metabolic syndrome for incidence density was increased significantly as hs-CRP increased, such trend disappeared after adjusting for confounding variables. The risk of metabolic syndrome was significantly higher (1.48 times) in the hs-CRP increased group than that in the decreased or unchanged group. This significance remained after controlling for covariates. CONCLUSION: Relatively higher hs-CRP level within normal range may predict the increase of metabolic syndrome compared to lower hs-CRP. Increased hs-CRP level may increase the incidence of metabolic syndrome.

High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men.

We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP) levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD) in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138) of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001). As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range) may require appropriate follow-up and management to prevent NAFLD development.

Grid Cell Responses in 1D Environments Assessed as Slices through a 2D Lattice.

Grid cells, defined by their striking periodic spatial responses in open 2D arenas, appear to respond differently on 1D tracks: the multiple response fields are not periodically arranged, peak amplitudes vary across fields, and the mean spacing between fields is larger than in 2D environments. We ask whether such 1D responses are consistent with the system's 2D dynamics. Combining analytical and numerical methods, we show that the 1D responses of grid cells with stable 1D fields are consistent with a linear slice through a 2D triangular lattice. Further, the 1D responses of comodular cells are well described by parallel slices, and the offsets in the starting points of the 1D slices can predict the measured 2D relative spatial phase between the cells. From these results, we conclude that the 2D dynamics of these cells is preserved in 1D, suggesting a common computation during both types of navigation behavior.

Specific evidence of low-dimensional continuous attractor dynamics in grid cells.

We examined simultaneously recorded spikes from multiple rat grid cells, to explain mechanisms underlying their activity. Among grid cells with similar spatial periods, the population activity was confined to lie close to a two-dimensional (2D) manifold: grid cells differed only along two dimensions of their responses and otherwise were nearly identical. Relationships between cell pairs were conserved despite extensive deformations of single-neuron responses. Results from novel environments suggest such structure is not inherited from hippocampal or external sensory inputs. Across conditions, cell-cell relationships are better conserved than responses of single cells. Finally, the system is continually subject to perturbations that, were the 2D manifold not attractive, would drive the system to inhabit a different region of state space than observed. These findings have strong implications for theories of grid-cell activity and substantiate the general hypothesis that the brain computes using low-dimensional continuous attractors.

Heart rate variability and urinary catecholamines from job stress in korean male manufacturing workers according to work seniority.

The aim of this study was to evaluate the relationships between job stress and indicators of autonomic nervous system activity in employees of the manufacturing industry. A total of 140 employees from a company that manufactures consumer goods (i.e., diapers and paper towels) were recruited for participation in this study. Job stress was assessed using Karasek's Job Content Questionnaire. Heart rate variability (HRV) was measured using a heart rate monitor, and urinary catecholamines were measured by an HPLC-ECD. Information on demographic characteristics, previous job history, smoking status and alcohol consumption was also collected. Job stress did not have a significant effect on HRV or catecholamines. However, low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. Low- and high-frequency HRV were higher in the high-strain group than in the low-strain group, but these differences were not statistically significant. The results of the present study indicate that low-frequency HRV was significantly higher in the high-strain group of subjects with a short duration of employment. In addition, the results of this study show that HRV can be used as a potential physiologic indicator of job stress in employees with a short duration of employment.

A pilot study on the association between job stress and repeated measures of immunological biomarkers in female nurses.

OBJECTIVE: To evaluate the immunosuppressive effects of job stress in female nurses, an 8-month longitudinal study was conducted at a major university hospital. METHODS: Four groups of ten subjects each were constructed to represent high versus low objective stress and high versus low subjective stress based on their responses to a job stress questionnaire and objective stress ratings of the hospital's work units. Number of white blood cells (i.e., T cells, B cells, and natural killer cells), and lymphocytic proliferation to mitogens (concanavalin A, phytohemagglutinin, and pokeweed) and toxoid (tetanus) were measured by flow cytometry and radioimmunoassay. Serum levels of hydrocortisol, IL-1ß, IFN-γ, and TNF-α, and salivary IgA were measured by enzyme-linked immunosorbent assay. The data were analyzed by repeated measures analysis of variance controlling for age and smoking. RESULTS: The level of white blood cells was lower among high objective stress group (median: 7,170/m(3); range: 5,386-10,057) compared with that among low objective stress group (8,063; 5,888-9,875) (P = 0.03), however, no other cellular blood variables were found to be significant. In terms of humoral immuno-biomarkers, the level of TNF-α was moderately lower among high objective stress group (1.7 ng/ml; 0.3-2.7) compared with that among low objective stress group (2.2; 0.5-3.5) (P = 0.07), whereas the level of total sIgA was significantly higher among higher objective stress group (72.9 end-point titer/mg/ml/min; 14.4-153.4) compared with that among low objective stress group (44.8; 9.9-123.8) (P = 0.02). CONCLUSION: The results of the study suggest that psychological job stress affects the levels of some immunological biomarkers in female nurses.

Depressive symptoms and self-reported occupational injury in small and medium-sized companies.

OBJECTIVES: This survey was designed to determine whether depressive symptoms had an effect on the risk of self-reported occupational injury in South Korea. METHODS: We conducted a prospective follow-up survey of workers at 44 small- to medium-sized companies classified into manufacturing or service businesses; 1,350 questionnaires were used in the final analysis. The first survey requested information regarding personal characteristics, work characteristics, and depressive symptoms (CES-D); the second survey queried participants in the first survey about self-reported occupational injuries (including minor scratches or cuts) experienced in the previous 4 months. Risk ratios (RRs) were calculated through Poisson regression analysis. The number of occupational injuries during the previous 4 months served as the dependent variable, and depressive symptoms served as the independent variable. RESULTS: After adjustment for demographic factors, the RRs were 1.75 (95% CI: 1.41-2.18) and 2.68 (95% CI: 1.98-3.64) in male and female, respectively. Additional adjustment for work-related variables did not alter the RR considerably in females (2.65; 95% CI: 1.95-3.59). Among the male workers, however, the RR was not significant (1.21; 95% CI: 0.95-1.55). On the other hand, when the analysis was limited to blue-collar workers, after adjustment for demographic and work-related factors, the RRs remained significant in both genders (male: 1.34; 95% CI: 1.03-1.74; female: 2.04; 95% CI: 1.41-2.95). CONCLUSIONS: We found that the risk of self-reported occupational injury experience was higher in workers who reported depressive symptoms. Additional study using objective data is required to confirm our results.

Time-dependent association between metabolic syndrome and risk of CKD in Korean men without hypertension or diabetes.

BACKGROUND: The time-dependent association between metabolic syndrome and risk of chronic kidney disease (CKD) is not clear. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: The study cohort was composed of 10,685 healthy men without CKD, hypertension, or diabetes who participated in a health-checkup program at a large work site. PREDICTOR: Metabolic syndrome. OUTCOMES & MEASUREMENTS: CKD was defined as an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m(2). A standard Cox proportional hazards model and a time-dependent Cox model were used to calculate adjusted hazard ratios (HRs) in the CKD model. RESULTS: During 40,616.8 person-years of follow-up, 291 incident cases of CKD developed; 787 patients (7.4%) had metabolic syndrome at baseline and 1,444 (14.4%) developed incident metabolic syndrome during follow-up. After adjustment for age, baseline GFR, gamma-glutamyltransferase level, and uric acid level, metabolic syndrome at baseline was associated with a significantly increased risk of CKD (HR, 1.99; 95% confidence interval, 1.46 to 2.73). Metabolic syndrome over time as a time-dependent variable also predicted the development of CKD (HR, 1.83; [corrected] 95% confidence interval, 1.34 to 2.49) [corrected] The relationship between metabolic syndrome and incident CKD remained significant, even after further adjustment for the homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein level, current smoking, alcohol consumption, or regular exercise. In addition, there were graded relationships between number of metabolic syndrome traits or quintile of homeostasis model assessment of insulin resistance over time as a time-dependent variable and risk of CKD. Both increased triglyceride and low high-density lipoprotein cholesterol levels among metabolic syndrome traits were associated with significantly increased risk of CKD. These results were effectively unchanged, even after additional adjustment for incident hypertension and incident diabetes. LIMITATIONS: Estimated GFR was used instead of a directly measured GFR to define CKD. CONCLUSION: Metabolic syndrome is an independent risk factor for the development of CKD in Korean men without hypertension or diabetes, even with changes in status of metabolic syndrome over time.

Peliosis hepatis with hemorrhagic necrosis and rupture: a case report with emphasis on the multi-detector CT findings.

We report here on an uncommon case of peliosis hepatis with hemorrhagic necrosis that was complicated by massive intrahepatic bleeding and rupture, and treated by emergent right lobectomy. We demonstrate the imaging findings, with emphasis on the triphasic, contrast-enhanced multidetector CT findings, as well as reporting the clinical outcome in a case of peliosis hepatis with fatal hemorrhage.