medsci-skills 4.1.0

package/skills/analyze-stats/references/analysis_guides/repeated_measures.md

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+# Repeated Measures / Mixed Models Guide
+
+Analysis methods for longitudinal data where the same subjects are measured at multiple time points.
+
+---
+
+## When to Use
+
+- Same subjects measured at 2+ time points
+- Key research question: does change over time differ between groups? (Time x Group interaction)
+- Examples: treatment response over weeks, serial imaging measurements, before/after/follow-up
+
+---
+
+## Method Selection
+
+| Condition | Recommended method |
+|-----------|-------------------|
+| No missing data + few time points + sphericity met | RM ANOVA |
+| Missing data (MAR) + continuous outcome | **LMM (preferred)** |
+| Missing data + binary/count outcome | GEE (or GLMM) |
+| Individual trajectory estimation needed | LMM (random slope) |
+| Population-averaged effect only | GEE |
+| Non-normal outcome | GLMM or GEE |
+
+**Default recommendation: LMM** — handles missing data, does not require sphericity, allows unequal time spacing.
+
+---
+
+## Data Format
+
+All methods (LMM, GEE) require **long format**:
+
+| id | time | group | outcome |
+|----|------|-------|---------|
+| 1 | 0 | A | 45.2 |
+| 1 | 1 | A | 42.8 |
+| 1 | 2 | A | 38.1 |
+
+Convert from wide format before analysis.
+
+---
+
+## 1. RM ANOVA
+
+### Sphericity Check (Mandatory)
+- **Mauchly's test**: H0 = sphericity holds
+  - P >= 0.05 → use standard F-test
+  - P < 0.05 → apply correction
+
+### Corrections for Sphericity Violation
+1. **Greenhouse-Geisser (G-G)**: conservative, recommended
+2. **Huynh-Feldt**: slightly liberal
+3. **Multivariate test** (Pillai's trace): no sphericity assumption needed
+
+### Limitations
+- Complete cases only — any missing time point drops the entire subject
+- Difficult to add covariates
+- Equal time spacing required
+
+### Key Results to Report
+- Mauchly's test result (W statistic, P-value, epsilon)
+- Correction method used (if sphericity violated)
+- Within-subject effect: Time (F, df, P)
+- Between-subject effect: Group (F, df, P)
+- **Interaction: Time x Group** (most important)
+
+---
+
+## 2. Linear Mixed Model (LMM)
+
+### Structure
+```
+Y = Xβ (fixed effects) + Zb (random effects) + ε
+```
+
+### Random Effects Selection
+- **Random intercept only**: subjects differ in baseline (default, start here)
+- **Random intercept + slope**: subjects differ in both baseline and rate of change
+- Decision: visualize individual trajectories (spaghetti plot). If slopes vary → add random slope.
+- If model does not converge with random slope → simplify to random intercept only
+
+### Covariance Structure Selection
+| Structure | Property | When to use |
+|-----------|----------|-------------|
+| **CS** (Compound Symmetry) | Equal correlation between all time pairs | Equivalent to RM ANOVA |
+| **AR(1)** | Correlation decays with time lag | Equally spaced measurements |
+| **UN** (Unstructured) | Free correlation for each pair | Few time points only (many parameters) |
+
+Compare structures using **AIC/BIC** (lower = better).
+
+### Advantages over RM ANOVA
+- Handles missing data under MAR assumption
+- No sphericity requirement
+- Allows unequal time intervals
+- Easy covariate adjustment
+- Estimates individual trajectories
+
+---
+
+## 3. GEE (Generalized Estimating Equations)
+
+### Key Properties
+- Estimates **population-averaged (marginal) effects** — not individual-level
+- Specify working correlation: exchangeable, AR(1), unstructured
+- Works for non-normal outcomes (binary, count)
+- Requires **MCAR** assumption for missing data (or use weighted GEE for MAR)
+- Needs sufficient clusters: subjects >= 30-40
+
+### LMM vs GEE Decision
+| Question | LMM | GEE |
+|----------|-----|-----|
+| "How does each patient change?" | Yes | No |
+| "How does the group average change?" | Yes | Yes |
+| Binary/count outcome without GLMM | No | Yes |
+| MAR missing data tolerance | Yes | No (MCAR only) |
+
+---
+
+## Required Outputs
+
+1. **Spaghetti plot**: individual trajectories by group
+2. **Model summary table**: fixed effects (β, 95% CI, P), random effects variance
+3. **Time x Group interaction** result prominently reported
+4. Model fit: AIC/BIC for covariance structure comparison
+5. Missing data description (n per time point, mechanism assumed)
+
+---
+
+## Reporting Templates
+
+**RM ANOVA**: "Repeated-measures ANOVA was performed with Greenhouse-Geisser correction for violation of sphericity (Mauchly's test P < 0.001, ε = 0.42). There was a significant time × group interaction (F(X, Y) = Z, P = exact)."
+
+**LMM**: "A linear mixed-effects model with random intercepts for subjects and [CS/AR(1)] correlation structure was fitted. The time × group interaction was significant (β = -2.34, 95% CI -3.87 to -0.81; P = 0.003), indicating that the rate of change in [outcome] differed between groups."
+
+**GEE**: "GEE with exchangeable correlation structure was used to estimate population-averaged effects. The time × group interaction was ..."
+
+---
+
+## Common Reviewer Flags
+
+1. Sphericity test not reported (for RM ANOVA)
+2. Covariance structure selection rationale not stated (for LMM)
+3. Time × Group interaction not interpreted
+4. Missing data handling not described
+5. Using RM ANOVA with substantial missing data (should use LMM)
+6. Not reporting individual trajectories (spaghetti plot)
+
+---
+
+## Python Packages
+- `pingouin` — RM ANOVA with G-G correction
+- `statsmodels.formula.api.mixedlm` — LMM
+- `statsmodels.genmod.generalized_estimating_equations.GEE` — GEE
+
+## R Packages
+- `lme4` + `lmerTest` — LMM (standard)
+- `nlme` — LMM with correlation structures (CS, AR1, UN)
+- `geepack` — GEE
+- Base R `aov()` with `Error()` — RM ANOVA

package/skills/analyze-stats/references/analysis_guides/survey_weighted.md

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+# Survey-Weighted Analysis Guide
+
+Methods for analyzing complex survey data (KNHANES, NHANES, KCHS, and similar
+nationally representative health surveys) that use stratified, multistage
+probability sampling designs.
+
+---
+
+## When to Use
+
+- Data from a national health survey with sampling weights (e.g., KNHANES, NHANES, KCHS)
+- Goal: produce nationally representative prevalence, means, or associations
+- Cross-national comparisons using parallel survey datasets
+- NOT for: simple random samples, census data, or claims-based cohorts (NHIS, JMDC)
+
+Claims-based databases (NHIS, JMDC) are NOT surveys -- they do not have sampling
+weights or complex sampling design. Use standard regression for these.
+
+---
+
+## Key Concepts
+
+### Complex Survey Design Elements
+
+| Element | Description | Survey variable |
+|---------|-------------|-----------------|
+| **Stratification** | Groups the population into non-overlapping strata before sampling | `strata` |
+| **Clustering (PSU)** | Primary sampling units within strata (e.g., districts, census blocks) | `cluster` / `PSU` |
+| **Sampling weights** | Inverse probability of selection, adjusted for non-response and post-stratification | `weight` |
+
+Ignoring these elements produces biased standard errors, incorrect p-values, and
+non-representative point estimates.
+
+### Dataset-Specific Design Variables
+
+| Dataset | Strata variable | Cluster/PSU variable | Weight variable | Notes |
+|---------|----------------|---------------------|-----------------|-------|
+| **KNHANES** | `kstrata` | `psu` | `wt_itvex` (interview+exam) or `wt_ntr` (nutrition) | Years may be non-consecutive (PHQ-9 only in certain cycles) |
+| **NHANES** | `SDMVSTRA` | `SDMVPSU` | `WTMECXYR` (exam) or `WTINTXYR` (interview) | 2-year cycles; combine cycles with adjusted weights |
+| **KCHS** | varies by year | varies by year | `wt` | Annual community survey; single-stage cluster design |
+
+### Weight Selection Rules
+
+- **Interview-only variables**: use interview weight
+- **Exam/lab variables**: use exam weight (smaller denominator)
+- **Nutrition variables (KNHANES)**: use nutrition weight
+- **Multi-cycle NHANES**: divide weight by number of cycles combined (e.g., 4 cycles: weight/4)
+- **Single-cycle analysis**: use the cycle-specific weight as-is
+
+---
+
+## Step-by-Step Workflow
+
+### Step 1: Declare Survey Design
+
+Always declare the design before any analysis. This ensures correct variance estimation.
+
+**Python (statsmodels)**:
+```python
+# statsmodels does not have a native survey design object.
+# Use linearmodels or manual weight application.
+# For publication-quality survey analysis, R is strongly recommended.
+```
+
+**R (survey package)**:
+```r
+library(survey)
+
+# KNHANES
+design_kr <- svydesign(
+  id = ~psu,
+  strata = ~kstrata,
+  weights = ~wt_itvex,
+  data = df_kr,
+  nest = TRUE
+)
+
+# NHANES (2-year cycle)
+design_us <- svydesign(
+  id = ~SDMVPSU,
+  strata = ~SDMVSTRA,
+  weights = ~WTMECXYR,
+  data = df_us,
+  nest = TRUE
+)
+```
+
+**SAS**:
+```sas
+/* KNHANES */
+PROC SURVEYLOGISTIC DATA=kr;
+  STRATA kstrata;
+  CLUSTER psu;
+  WEIGHT wt_itvex;
+  MODEL outcome(event='1') = exposure covariates;
+RUN;
+
+/* NHANES */
+PROC SURVEYLOGISTIC DATA=us;
+  STRATA SDMVSTRA;
+  CLUSTER SDMVPSU;
+  WEIGHT WTMECXYR;
+  MODEL outcome(event='1') = exposure covariates;
+RUN;
+```
+
+### Step 2: Weighted Descriptive Statistics
+
+**R**:
+```r
+# Weighted means
+svymean(~continuous_var, design, na.rm = TRUE)
+
+# Weighted proportions
+svymean(~factor(categorical_var), design, na.rm = TRUE)
+
+# Weighted Table 1 by group
+library(tableone)
+svyCreateTableOne(
+  vars = c("age", "sex", "bmi", "income"),
+  strata = "exposure_group",
+  data = design,
+  test = TRUE
+)
+```
+
+**SAS**:
+```sas
+PROC SURVEYMEANS DATA=dataset;
+  STRATA strata_var;
+  CLUSTER cluster_var;
+  WEIGHT weight_var;
+  VAR continuous_var1 continuous_var2;
+RUN;
+
+PROC SURVEYFREQ DATA=dataset;
+  STRATA strata_var;
+  CLUSTER cluster_var;
+  WEIGHT weight_var;
+  TABLES group * categorical_var / CHISQ;
+RUN;
+```
+
+### Step 3: Weighted Regression — Sequential Model Building
+
+The standard cross-national analysis pattern uses sequential model building:
+
+| Model | Covariates | Purpose |
+|-------|-----------|---------|
+| Model 1 | Age, sex | Minimal adjustment |
+| Model 2 | Model 1 + income, education, smoking, alcohol, BMI, comorbidities | Full adjustment |
+
+**R (survey-weighted logistic regression)**:
+```r
+# Model 1: age + sex
+model1 <- svyglm(
+  outcome ~ exposure + age + sex,
+  design = design,
+  family = quasibinomial()
+)
+
+# Model 2: full adjustment
+model2 <- svyglm(
+  outcome ~ exposure + age + sex + income + education +
+            smoking + alcohol + bmi + cvd_history,
+  design = design,
+  family = quasibinomial()
+)
+
+# Extract weighted OR (wOR) with 95% CI
+extract_wor <- function(model, var) {
+  coef_val <- coef(model)[var]
+  se_val <- summary(model)$coefficients[var, "Std. Error"]
+  or <- exp(coef_val)
+  ci_lo <- exp(coef_val - 1.96 * se_val)
+  ci_hi <- exp(coef_val + 1.96 * se_val)
+  p_val <- summary(model)$coefficients[var, "Pr(>|t|)"]
+  data.frame(wOR = or, CI_lower = ci_lo, CI_upper = ci_hi, P = p_val)
+}
+```
+
+**SAS (PROC SURVEYLOGISTIC)**:
+```sas
+/* Model 2: full adjustment */
+PROC SURVEYLOGISTIC DATA=dataset;
+  STRATA strata_var;
+  CLUSTER cluster_var;
+  WEIGHT weight_var;
+  CLASS sex(ref='Male') income(ref='High') smoking(ref='Never') / PARAM=REF;
+  MODEL outcome(event='1') = exposure age sex income education smoking alcohol bmi;
+  ODDSRATIO exposure / CL=WALD;
+RUN;
+```
+
+### Step 4: Subgroup / Stratified Analyses
+
+```r
+# Stratified by sex
+svyglm(
+  outcome ~ exposure + age + income + education + smoking + alcohol + bmi,
+  design = subset(design, sex == "Male"),
+  family = quasibinomial()
+)
+# Repeat for Female
+# Note: exclude the stratification variable from covariates
+```
+
+Reporting pattern: "Weighted odds ratios are adjusted for all covariates except
+for the stratification variable."
+
+### Step 5: Advanced Analyses (Optional)
+
+**Restricted cubic spline (dose-response)**:
+```r
+library(rms)
+design_rms <- svydesign(id = ~psu, strata = ~kstrata,
+                         weights = ~wt_itvex, data = df)
+model_rcs <- svyglm(
+  outcome ~ rcs(continuous_exposure, 3) + age + sex + covariates,
+  design = design_rms,
+  family = quasibinomial()
+)
+```
+
+**Weighted quantile sum (WQS) regression**:
+```r
+library(gWQS)
+# WQS for composite exposure (e.g., LE8 components)
+result_wqs <- gwqs(
+  outcome ~ wqs + age + sex + covariates,
+  mix_name = c("comp1", "comp2", "comp3", "comp4"),
+  data = df,
+  q = 4,           # quartiles
+  b = 500,         # bootstrap iterations
+  seed = 42,
+  family = "binomial",
+  weights = df$weight_var
+)
+```
+
+---
+
+## Weighted SMD (Standardized Mean Difference)
+
+For balance assessment in weighted analyses:
+
+```r
+library(survey)
+library(tableone)
+
+# SMD in survey design
+tab <- svyCreateTableOne(
+  vars = covariates,
+  strata = "treatment",
+  data = design,
+  smd = TRUE
+)
+print(tab, smd = TRUE)
+```
+
+**Manual calculation (Python)**:
+```python
+def weighted_smd(x, treatment, weights, is_binary=False):
+    """Calculate weighted standardized mean difference."""
+    t_mask = treatment == 1
+    c_mask = treatment == 0
+    
+    w1, w0 = weights[t_mask], weights[c_mask]
+    x1, x0 = x[t_mask], x[c_mask]
+    
+    wm1 = np.average(x1, weights=w1)
+    wm0 = np.average(x0, weights=w0)
+    
+    if is_binary:
+        denom = np.sqrt((wm1 * (1 - wm1) + wm0 * (1 - wm0)) / 2)
+    else:
+        wv1 = np.average((x1 - wm1) ** 2, weights=w1)
+        wv0 = np.average((x0 - wm0) ** 2, weights=w0)
+        denom = np.sqrt((wv1 + wv0) / 2)
+    
+    return (wm1 - wm0) / denom if denom > 0 else 0.0
+```
+
+---
+
+## Cross-National Analysis Pattern
+
+When comparing two countries using parallel surveys:
+
+1. **Never pool** raw data across countries into a single regression
+2. Analyze each country **independently** with country-specific survey design
+3. Present results **side-by-side** in the same table
+4. Compare effect magnitudes narratively (not via interaction terms)
+
+### Standard Output Table Format
+
+| Variable | Korea (KNHANES) | | US (NHANES) | |
+|----------|------|------|------|------|
+| | Model 1 wOR (95% CI) | Model 2 wOR (95% CI) | Model 1 wOR (95% CI) | Model 2 wOR (95% CI) |
+| Exposure | 1.42 (1.21-1.67) | 1.35 (1.14-1.59) | 1.28 (1.10-1.49) | 1.22 (1.04-1.43) |
+
+---
+
+## Reporting Templates
+
+**Methods**:
+"To account for the complex survey designs and ensure nationally representative
+estimates, appropriate stratification, clustering, and sampling weights were
+applied. Weighted logistic regression models were used to estimate weighted odds
+ratios (wORs) and 95% confidence intervals (CIs). Model 1 adjusted for age and
+sex, while Model 2 further included [covariates]. All analyses were performed
+using SAS version 9.4 (SAS Institute Inc.) [and R version X.X.X (R Foundation
+for Statistical Computing)]. A two-sided P value of less than 0.05 was
+considered statistically significant."
+
+**Results**:
+"In the weighted analysis of [N] participants from [DATASET], [EXPOSURE] was
+significantly associated with [OUTCOME] (wOR [X.XX]; 95% CI [X.XX-X.XX]) after
+adjusting for [covariates] (Model 2)."
+
+---
+
+## Common Reviewer Flags
+
+1. Survey weights not applied (unweighted analysis of survey data)
+2. Strata/cluster variables not specified (incorrect SE estimation)
+3. Wrong weight variable used (interview weight for lab variables)
+4. Multi-cycle NHANES weights not adjusted (divided by number of cycles)
+5. Data pooled across countries instead of analyzed separately
+6. Weighted proportions not reported (using raw counts instead)
+7. Subgroup analysis includes the stratification variable as covariate
+8. Missing data handling not stated (complete case vs imputation)
+
+---
+
+## Python vs R Recommendation
+
+| Task | Recommended | Reason |
+|------|-------------|--------|
+| Survey-weighted regression | **R (survey)** | Native support, correct variance estimation |
+| Survey-weighted Table 1 | **R (tableone)** | `svyCreateTableOne()` handles design |
+| WQS regression | **R (gWQS)** | Only available in R |
+| Dose-response (RCS) | **R (rms + survey)** | Integrated with survey design |
+| Quick descriptives | Python (statsmodels) | Adequate for simple weighted means |
+
+For publication-quality survey analysis, **R is strongly recommended** over Python.
+Python's statsmodels supports basic weighted regression but lacks full survey
+design support (no strata/cluster specification for variance estimation).
+
+---
+
+## R Packages
+
+- `survey` -- core survey design and analysis
+- `tableone` -- survey-weighted baseline tables with SMD
+- `rms` -- restricted cubic splines with survey design
+- `gWQS` -- weighted quantile sum regression
+- `srvyr` -- tidyverse-compatible survey analysis wrapper
+
+## SAS Procedures
+
+- `PROC SURVEYMEANS` -- weighted means and proportions
+- `PROC SURVEYFREQ` -- weighted frequency tables and chi-square
+- `PROC SURVEYLOGISTIC` -- weighted logistic regression (wOR)
+- `PROC SURVEYREG` -- weighted linear regression
+- `PROC SURVEYPHREG` -- weighted Cox proportional hazards

package/skills/analyze-stats/references/analysis_guides/test_selection.md

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+# Statistical Test Selection Guide
+
+Decision tree for selecting the appropriate statistical test based on data structure.
+Reference: Petrie & Sabin flowchart, Kirkwood Summary Guide.
+
+---
+
+## Step 1: Outcome Variable Type
+
+| Outcome type | Next step |
+|---|---|
+| Continuous (measurement, score) | Step 2A |
+| Binary / Categorical | Step 2B |
+| Time-to-event (survival) | → Survival analysis type |
+| Agreement / Reliability | → Inter-rater Agreement type |
+| Diagnostic accuracy (Se/Sp/AUC) | → Diagnostic Accuracy type |
+
+---
+
+## Step 2A: Continuous Outcome
+
+| Groups | Pairing | Normal? | Test | analyze-stats type |
+|--------|---------|---------|------|--------------------|
+| 1 | - | Yes | One-sample t-test | Group Comparison |
+| 1 | - | No | Wilcoxon signed-rank (one-sample) | Group Comparison |
+| 2 | Independent | Yes | Independent t-test | Group Comparison |
+| 2 | Independent | No | Mann-Whitney U | Group Comparison |
+| 2 | Paired | Yes | Paired t-test | Group Comparison |
+| 2 | Paired | No | Wilcoxon signed-rank | Group Comparison |
+| 3+ | Independent | Yes | One-way ANOVA + post-hoc | Group Comparison |
+| 3+ | Independent | No | Kruskal-Wallis + post-hoc | Group Comparison |
+| 3+ | Repeated | Yes | RM ANOVA | **Repeated Measures** |
+| 3+ | Repeated | No | Friedman test | **Repeated Measures** |
+| - | Correlation | Yes | Pearson r | Correlation |
+| - | Correlation | No | Spearman rho | Correlation |
+| - | Regression | - | Multiple linear regression | **Linear Regression** |
+
+---
+
+## Step 2B: Categorical Outcome
+
+| Groups | Pairing | Condition | Test | analyze-stats type |
+|--------|---------|-----------|------|--------------------|
+| 1 | - | - | Binomial / z-test for proportion | Group Comparison |
+| 2 | Independent | Expected >= 5 | Chi-squared | Group Comparison |
+| 2 | Independent | Expected < 5 | Fisher's exact | Group Comparison |
+| 2 | Paired | - | McNemar's test | Group Comparison |
+| 2+ | Independent | Ordered | Chi-squared trend | Group Comparison |
+| 3+ | Independent | - | Chi-squared | Group Comparison |
+| 3+ | Paired | - | Cochran's Q | Group Comparison |
+| - | Regression | Binary outcome | Logistic regression | **Logistic Regression** |
+
+---
+
+## Step 3: Confounder Control
+
+| Situation | Method | analyze-stats type |
+|-----------|--------|--------------------|
+| Continuous outcome + multivariable | Multiple linear regression | **Linear Regression** |
+| Binary outcome + multivariable | Logistic regression | **Logistic Regression** |
+| Survival outcome + multivariable | Cox proportional hazards | Survival |
+| Observational study + treatment comparison | Propensity score | **Propensity Score** |
+| Repeated measures + missing data | LMM / GEE | **Repeated Measures** |
+
+---
+
+## Normality Assessment
+
+| Method | When | Criterion |
+|--------|------|-----------|
+| Shapiro-Wilk | n < 50 | p >= 0.05 → normal |
+| Kolmogorov-Smirnov | n >= 50 | p >= 0.05 → normal |
+| Q-Q plot | Always (visual) | Points on diagonal |
+| Skewness/Kurtosis | Supplementary | |skew| < 2, |kurt| < 7 |
+
+Practical rule: n > 30 → t-test is generally robust (CLT), unless extreme skew or outliers.
+
+---
+
+## Common Reviewer Flags
+
+- Using independent test on paired data
+- Using chi-squared when expected cell count < 5 (should use Fisher's exact)
+- Not reporting assumption check results
+- Missing multiple comparison correction for 3+ groups
+- Not specifying the test selection rationale in Methods

package/skills/analyze-stats/references/style/figure_style.mplstyle

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+# Publication-ready matplotlib style for medical research figures
+# Usage: plt.style.use('path/to/figure_style.mplstyle')
+
+# --- Font ---
+font.family: sans-serif
+font.sans-serif: Arial, Helvetica, DejaVu Sans
+font.size: 9
+
+# --- Figure ---
+figure.figsize: 3.5, 3.5
+figure.dpi: 300
+figure.facecolor: white
+figure.edgecolor: white
+figure.autolayout: True
+
+# --- Axes ---
+axes.facecolor: white
+axes.edgecolor: 333333
+axes.linewidth: 0.8
+axes.grid: True
+axes.titlesize: 10
+axes.titleweight: bold
+axes.labelsize: 9
+axes.labelweight: normal
+axes.labelpad: 4.0
+axes.spines.top: False
+axes.spines.right: False
+axes.prop_cycle: cycler('color', ['0072B2', 'D55E00', '009E73', 'CC79A7', 'F0E442', '56B4E9', 'E69F00', '000000'])
+
+# --- Grid ---
+grid.color: cccccc
+grid.linewidth: 0.5
+grid.linestyle: -
+grid.alpha: 0.4
+
+# --- Lines ---
+lines.linewidth: 1.5
+lines.markersize: 4
+lines.markeredgewidth: 0.5
+
+# --- Ticks ---
+xtick.labelsize: 8
+xtick.direction: out
+xtick.major.size: 4
+xtick.major.width: 0.8
+xtick.minor.visible: False
+ytick.labelsize: 8
+ytick.direction: out
+ytick.major.size: 4
+ytick.major.width: 0.8
+ytick.minor.visible: False
+
+# --- Legend ---
+legend.fontsize: 8
+legend.frameon: False
+legend.loc: best
+legend.borderpad: 0.3
+legend.handlelength: 1.5
+
+# --- Scatter ---
+scatter.marker: o
+scatter.edgecolors: face
+
+# --- Save ---
+savefig.dpi: 300
+savefig.format: pdf
+savefig.bbox: tight
+savefig.pad_inches: 0.05
+savefig.transparent: False