Although comorbid medical diseases are important determinants of outcome among the critically ill, the role of psychiatric comorbidity is not well defined. The objective of this study was to determine the occurrence of psychiatric comorbidity and its effect on the outcome of patients admitted to adult intensive care units (ICU) in Queensland. Admissions among adults to 12 ICUs in Queensland during 2015–2021 were included and clinical and outcome information was obtained through linkages between the ANZICS Adult Patient Database, the state-wide Queensland Hospital Admitted Patient Data Collection, and death registry. A total of 89,123 admissions were included among 74,513 individuals. Overall, 7,178 (8.1

Objective:Mean arterial pressure (MAP) management is a key aspect of treatment in critically ill patients receiving vasopressor therapy. Guidelines in different clinical subgroups have proposed various target MAP values. This study aimed to describe delivered MAP values and corresponding vasopressor doses in such patients. Design:Multicenter, retrospective cohort study of adult intensive care unit (ICU) admissions. Setting:12 ICUs in Queensland, Australia, from January 1, 2015, to December 31, 2021. Participants:Patients receiving vasopressors for at least six continuous hours in the ICU. We studied the delivered MAP values using hourly data based on averaging all validated values obtained from the ICU monitors and average hourly doses of vasopressors. Main Outcome Measure:The primary outcome was the mean MAP during the entire cohort's first 72 hours of ICU admission, whilst vasopressors were administered. Results:In 26,519 patients who received vasopressors for at least six continuous hours, the median age was 62 years, and 9,373 (35%) were admitted after elective surgery. The median time from ICU admission to vasopressor commencement was 2 hours, and the median duration of vasopressor therapy was 27 hours. At 72 hours, 6,627 (25.0%) patients remained on vasopressors. The mean hourly MAP was 72 mmHg in the first six hours, then steadily increased to ≈75 mmHg at 72 hours. In the first 72 hours, 11,032 (41.6%) patients had a mean MAP of 70-74 mmHg, and 5,914 (22.3%) had a mean MAP of 75-79 mmHg. For every clinical subgroup, a MAP of 70-74 mmHg was the most common mean MAP, and the proportion of patients with a mean MAP of 60-65mmHg was less than 5%. Conclusions:In a large, multicenter study of heterogeneous critically ill patients on vasopressors, the mean hourly MAP was > 70 mmHg. This mean hourly MAP was observed consistently over diverse clinical subgroups and is higher than recommended by guidelines.

BACKGROUND:Advanced glycation end-products (AGEs) can enter patients' circulation through exogenous sources, such as enteral nutrition formulae. Circulating AGEs, specifically carboxymethyllysine, can promote insulin resistance and activation of pro-inflammatory pathways leading to oxidative stress, cell death, and organ failure. Suboptimal kidney function increases the risk of elevated circulating AGEs because levels are controlled through urinary excretion. Our aim was to determine associations between carboxymethyllysine intake and glycemic control as well as clinical outcomes in critically ill patients and explore these in the subset of patients with an acute kidney injury (AKI). METHODS:This was a retrospective cohort study. Data were extracted from electronic medical records. Patients were eligible if they were ≥18 years and received enteral nutrition, with known carboxymethyllysine content, for ≥3 days. AKI was defined using the Kidney Disease: Improving Global Outcomes guidelines. Linear and logistic regression models were used to determine adjusted associations. RESULTS:Between 2015 and 2021, 2636 patients met the eligibility criteria, with 848 (32%) patients having an AKI. Most were male (n = 1752, 67%) with a median (interquartile range) Acute Physiology And Chronic Health Evaluation III score of 59 (45-77). For every 10-μmol increase in carboxymethyllysine provision, mean blood glucose increased by 0.05 mmol (95% CI, 0.03-0.07), and the odds of dying increased by 16% (odds ratio = 1.16; 95% CI, 1.06-1.27). A subgroup analysis indicated these associations persisted in patients with AKI but not in those without. CONCLUSION:Carboxymethyllysine intake was associated with increased mean blood glucose and odds of dying in our study cohort.

Background In critically ill patients with acute kidney injury (AKI), a fluid balance (FB) > 2 L at 72 h after AKI diagnosis is associated with adverse outcomes. Identification of patients at high-risk for such fluid accumulation may help prevent it. Methods We used Australian electronic medical record (EMR)-based clinical data to develop the “AKI-FB risk score”, validated it in a British cohort and used it to predict a positive FB >2 L at 72 h after AKI diagnosis. Results We developed the AKI-FB score in 32,030 patients with a median age of 63 years and a median APACHE 2 score of 16. We validated it in 4465 patients, with significant differences in admission diagnoses and interventions. The key score variables were admission after trauma, sepsis or septic shock, and, on the day of AKI diagnosis, highest creatinine, daily cumulative FB, mechanical ventilation, noradrenaline use, noradrenaline equivalent dose >0.07 μg/kg/min, lactate ≥2 mmol/L, transfusion, and nutritional support. A score threshold of 32 had a sensitivity of 75 % and a specificity of 72 % for predicting a > 2 L positive FB with an AUC-ROC of 0.805; 95 % CI 0.799 to 0.810. External validation demonstrated an AUC of 0.761 (95 % CI 0.746 to 0.775). Conclusion We developed and validated the “AKI-FB risk score” to predict patients who developed a positive FB >2 L within 72 h of AKI diagnosis. This prediction score was robust and facilitated the identification of high-risk AKI patients who could be the tarted for preventive measures and be included in future clinical trials of FB management.

BACKGROUND:Serum creatinine measured by point-of-care testing (CrP) correlates with central laboratory serum creatinine (CrC) measurement and can be performed frequently, which might lead to an earlier diagnosis of acute kidney injury (AKI). We aimed to test whether the combination of CrP and CrC measurement would achieve earlier and more freuent AKI diagnosis than routine CrC testing alone. METHODS:Retrospective study of critically ill patients with two or more CrP measurements 24 h before an AKI was diagnosed on CrC. RESULTS:1591 patients with a median APACHE 3 score of 67 (IQR 52-85) and a median number of CrP of 5 (IQR 3-6) measurements. The median individual differences in time to AKI diagnosis between CrC and CrP was -5 h (-11--1). As the number of point-of-care tests increased in the 24 h before CrC-defined AKI diagnosis, the difference in hours increased (-3 (IQR -6--1) to -8 (IQR -13- -2); p < 0.001). Compared to CrC alone, the use of both CrC and CrP detected more increases in AKI severity to each AKI stage (stage 1: 1767 (34 %) vs 1.170 (30 %); stage 2: 1.301 (25 %) vs 809 (21 %) and stage 3: 2071 (40 %) vs 1920 (49 %); p < 0.001). CONCLUSION:Combined with CrC, CrP measurement resulted in the earlier diagnosis of AKI during ICU admission. Compared to CrC alone, using CrP measurements in combination with CrC was also associated with a higher maximum AKI stage and more detection of worsening AKI.

BACKGROUND:Hypernatremia is relatively common in acutely ill patients and associated with mortality. Guidelines recommend a slow rate of correction (≤ 0.5 mmol/L per hour). However, a faster correction rate may be safe and improve outcomes. OBJECTIVES:To evaluate the impact of sodium correction rates on mortality and hospital length of stay and to assess types of hypernatremia treatment and treatment side effects. METHODS:We conducted a systematic review and meta-analysis according to PRISMA guidelines, searching Ovid MEDLINE, Embase, and CENTRAL databases from inception to August 2024. Studies reporting sodium correction rates and clinical outcomes in hospitalized adults were included. A random-effects meta-analysis assessed mortality and hospital length of stay, with subgroup analyses exploring correction timing and severity. Treatment method and side effects were analyzed qualitatively. RESULTS:We reviewed 4445 articles and included 12 studies. Faster correction rates (> 0.5 mmol/L/h) overall showed no significant change in mortality and a high level of heterogeneity (OR 0.68, 95 % CI: 0.38-1.24, I2 = 95 %). However, subgroup analyses found significantly lower mortality with faster correction of hypernatremia at the time of hospital admission (OR 0.48, 95 % CI: 0.35-0.68, I2 = 2 %), with fast correction within the first 24 h of diagnosis (OR 0.48, 95 % CI: 0.31-0.73, I2 = 65 %), and for severe hypernatremia (OR 0.55, 95 % CI: 0.33-0.92, I2 = 79 %). There was no significant different in hospital length of stay by correction rate. No major neurological complications were reported when the correction rate was < 1 mmol/L/h. CONCLUSION:Faster sodium correction appears safe and may benefit patients with severe admission-related hypernatremia, particularly within the first 24 h. Further studies are needed to refine correction protocols.

Purpose: Clinical trials focusing on critically ill patients with metabolic acidosis, a common exclusion criterion is the presence of a PaCO2 > 45 mmHg. The aim of this study was to assess the impact of mild hypercapnia on patient characteristics, severity, and clinical outcomes in critically ill patients with metabolic acidosis. Material and methods: Multicentre, retrospective, observational study conducted in 12 intensive care units (ICUs) in Queensland, Australia. Patients with metabolic acidosis and concurrent vasopressor requirement were included and the exposure of interest was the PaCO2 level at the time of meeting the eligibility criteria divided in two groups: PaCO2 <45 mmHg and PaCO2 46-50 mmHg. Primary clinical outcome was major adverse kidney events within 30 days (MAKE30). Results: We studied 5601 patients, with 3605 (64.4 %) in the PaCO2 <45 mmHg group and 1996 (35.6 %) in the PaCO2 46-50 mmHg group. The incidence of MAKE30 was lower in the PaCO2 46-50 mmHg group (29 % vs. 34 %; OR, 0.79 [95 %CI, 0.69 to 0.90]; p < 0.001) as was the use of renal replacement therapy, and the incidence of acute kidney injury. After adjustment for confounders, no outcome was different between the groups. The maximum fall of pH associated with an increase of 1 mmHg of PaCO2 in the PaCO2 46-50 mmHg group was 0.006. Conclusion: In patients with metabolic acidosis, after adjustment for potential confounders, mild hypercapnia does not increase the MAKE-30 rate and does not have a major impact on pH.

Introduction Hypophosphatemia is common in critically ill patients. We have described the epidemiology of hypophosphatemia in patients admitted to the Intensive Care Units. Methods A multicentre, retrospective cohort study of 12 ICUs in Queensland, Australia from January 1st, 2015, to December 31st, 2021. Exclusions included readmissions, renal replacement therapy, end-stage renal disease, and palliative intent admissions and transfers from other ICUs. Patients were classified into four groups based on the severity of the first episode of low serum phosphate (PO4): “None” (PO4: ≥ 0.81 mmol/L, ``Mild” (PO4: ≥ 0.50 & < 0.81 mmol/L) “Moderate” (PO4: ≥ 0.30 & < 0.50 mmol/L) and “Severe” (PO4: < 0.30 mmol/L). A mixed-effect logistic regression model, including hospital as a random effect, was developed to examine factors associated with 90-day case fatality. Results Of the 89,776 patients admitted, 68,699 patients were included in this study, with 23,485 (34.2%) having hypophosphatemia with onset mostly on Day 2 of ICU admission and correcting to normal 3 days after hypophosphatemia was identified. There was substantial variation among participating ICUs in phosphate replacement; the threshold, and the route by which it was replaced. Day-90 case fatality increased with severity of hypophosphatemia (None: 3,974 (8.8%), Mild: 2,306 (11%), Moderate: 377 (14%); Severe: 108 (21%) (p < 0.001)). Multivariable regression analysis showed that compared to those without hypophosphatemia, patients with moderate (odds ratio (OR) 1.24; 95% confidence intervals (CI) 1.07-1.44; p = 0.004) or severe (OR 1.49; 95% CI 1.13-1.97; p = 0.005) hypophosphatemia had increased risk of 90-day case fatality. Conclusion Hypophosphatemia was common, and mostly occurred on day 2 with early correction of serum phosphate. Phosphate replacement practices were variable among ICUs. Moderate and severe hypophosphatemia was associated with increased 90-day case fatality.

Introduction: In critically ill patients undergoing continuous renal replacement therapy (CRRT), a positive fluid balance (FB) is associated with adverse outcomes. However, current FB management practices in CRRT patients are poorly understood. We aimed to study FB and its components in British and Australian CRRT patients to inform future trials. Methods: We obtained detailed electronic health record data on all fluid-related variables during CRRT and hourly FB for the first 7 days of treatment. Results: We studied 1,616 patients from three tertiary intensive care units (ICUs) in two countries. After the start of CRRT, the mean cumulative FB became negative at 31 h and remained negative over 7 days to a mean nadir of -4.1 L (95% confidence interval (CI) of -4.6 to -3.5). The net ultrafiltration (NUF) rate was the dominant fluid variable (-67.7 mL/h; standard deviation (SD): 75.7); however, residual urine output (-34.7 mL/h; SD: 54.5), crystalloid administration (48.1 mL/h; SD: 44.6), and nutritional input (36.4 mL/h; SD: 29.7) significantly contributed to FB. Patients with a positive FB after 72 h of CRRT were more severely ill, required high-dose vasopressors, and had high lactate concentrations (5.0 mmol/L; interquartile range: 2.3-10.5). A positive FB was independently associated with increased hospital mortality (odds ratio: 1.70; 95% CI; p = 0.004). Conclusion: In the study ICUs, most CRRT patients achieved a predominantly NUF-dependent negative FB. Patients with a positive FB at 72 h had greater illness severity and haemodynamic instability. Achieving equipoise for conducting trials that target a negative early FB in such patients may be difficult.

Objective The optimal timing of vasopressin initiation as an adjunctive vasopressor remains unclear. We aimed to study the association between the timing of vasopressin commencement, pre-specified physiological parameters, and hospital mortality. Design We conducted a multicentre, retrospective, observational study. Setting Twelve ICUs in Queensland, Australia between January 2015 and December 2021. Participants Adult patients with septic shock who received vasopressin as an adjunctive vasopressor within 72 hours of ICU admission. Main Outcome Hospital mortality. Results Overall, 2747 patients fulfilled the inclusion criteria. Of these, 1850 (67%) started vasopressin within six hours of vasopressor therapy start, while 897 (33%) started vasopressin between six hours and 72 hours. APACHE III score, peak lactate, and creatinine were higher in the early start group. Early vasopressin start was independently associated with decreased hospital mortality (aOR = 0.69, 95% CI = 0.57-0.83). Vasopressin infusion start was also associated with an immediate decrease in the noradrenaline-equivalent dose regardless of timing. There was a statistically significant favourable breakpoint at vasopressin start for the course of arterial pH, lactate, heart rate and crystalloid infusion rate (p<0.001). Conclusions In patients with septic shock, early adjunctive vasopressin initiation was independently associated with lower hospital mortality. Vasopressin starting at any time was also associated with reduced tachycardia, acidosis, and hyperlactatemia.

Background: Severe intensive care unit-acquired hypernatraemia (ICU-AH) is a serious complication of critical illness. However, there is no detailed information on how this condition develops. Objectives: The objective of this study was to study the prevalence, risk factors, trajectory, management, and outcome of severe ICU-AH (>155 mmol center dot L-1). Methods: A retrospective study was conducted in a 40-bed ICU in a university-affiliated hospital. Assessment of sodium levels, factors associated with severe ICU-AH, urinary electrolyte measurements, water therapy, fluid balance, correction rate, and delirium was made. Results: We screened 11,642 ICU admissions and identified 109 patients with severe ICU-AH. The median age was 57 years, 63% were male, and the median Acute Physiology and Chronic Health Evaluation III score was 64 (52; 80). On the day of ICU admission, 64% of patients were ventilated; 71% received vasopressors, and 22% had acute kidney injury. The median peak sodium level was 158 (156; 161) mmolL-1 at a median of 4(1; 11) days after ICU admission. Only eight patients (7%) had urine sodium measurement (median concentration: 17 mmol center dot L-1). On the day of peak hypernatraemia, 80% of patients were unable to drink due to invasive ventilation; 34% were on diuretics; 25% had fever, and 50% did not receive hypotonic fluids. When available, the median electrolyte-free water clearance was-1.1 L (-1.7;-0.5), representing half of the urine output. After peak hypernatraemia, the correction rate was-2.8 mmol center dot L-1 per day (95% confidence interval: [-2.9 to-2.6]) during the first 3 d. Conclusions: Severe hypernatraemia occurred in the setting of inability to drink, near-absent measurement of urinary free water losses, diuretic therapy, fever, renal impairment, and near-absent or limited or delayed water administration. Correction was slow. (c) 2024 Published by Elsevier B.V. on behalf of College of Intensive Care Medicine of Australia and New Zealand. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Objective: This study aimed to determine the associations between lactate clearance in hyperlactataemic patients with diabetic ketoacidosis (DKA) and intensive care unit (ICU), hospital length of stay (LOS), and case-fatality. Methods: A retrospective, multicentre, cohort study of adult patients admitted to ICU with hyperlactataemia and a primary diagnosis of DKA from twelve sites in Queensland, Australia was conducted utilising pre-existing datasets that were linked for research purposes. The patients were divided into early and late lactate clearance groups; the early lactate clearance group included patients whose lactate returned to <2.0 mmol/L within 12 h, and the remainder were classified as late lactate clearance group. Results: The final dataset included 511 patients, 427 in the early lactate clearance group and 84 in the late lactate clearance group. Late lactate clearance was associated with increasing ICU LOS (β = +15.82, 95% CI +0.05 to +31.59, p < 0.049), increasing hospital LOS (β = +7.24, 95% CI +0.11 to 14.37, p = 0.048) and increasing Acute Physiology and Chronic Health Evaluation(APACHE) III score (ICU LOS outcome variable β = +1.05, 95% CI +0.88 to +1.22, p < 0.001; hospital LOS outcome variable β = +3.40, 95% CI +2.22 to 4.57, p < 0.001). Hospital case-fatality was not significantly different (2.2% in the early clearance group vs. 1.7% in the late clearance group, p = 0.496). Conclusions: In hyperlactataemic patients with DKA, late lactate clearance was associated with a statistically significant increase in both ICU and hospital LOS, though the clinical significance in both is minor.

Objective:Frequent measurement of creatinine by point-of-care testing (POCT) may facilitate the earlier detection of acute kidney injury (AKI) in critically ill patients. However, no robust data exist to confirm its equivalence to central laboratory testing. We aimed to conduct a multicenter study to compare POCT with central laboratory creatinine (CrC) measurement. Design:Retrospective observational study, using hospital electronic medical records. Obtained paired point-of-care creatinine (CrP) from arterial blood gas machines and CrC. Setting:Four intensive care units in Queensland, Australia. Participants:Critically ill patients, where greater than 50% of POCT contained creatinine. Main outcome measures:Mean difference, bias, and limits of agreement between two methods, and biochemical confounders. Results:We studied 79,767 paired measurements in 19,118 patients, with a median Acute Physiology and Chronic Health Evaluation 3 score of 51. The mean CrC was 115.5 μmol/L (standard deviation: 100.2) compared to a CrP mean of 115 μmol/L (standard deviation: 100.7) (Pearson coefficient of 0.99). The mean difference between CrP and CrC was 0.49 μmol/L with 95% limits of agreement of -27 μmol/L and +28 μmol/L. Several biochemical variables were independently associated with the difference between tests (e.g., pH, potassium, lactate, glucose, and bilirubin), but their impact was small. Conclusion:In critically ill patients, measurement of creatinine by POCT yields clinically equivalent values to those obtained by central laboratory measurement and can be easily used for more frequent monitoring of kidney function in such patients. These findings open the door to the use of POCT for the earlier detection of acute kidney injury in critically ill patients.

Background: The location of onset of bloodstream infections (BSIs) associated with intensive care unit (ICU) admission may influence their clinical and epidemiological characteristics. Methods: A multicentre, retrospective cohort study was conducted in Queensland, Australia, and BSIs associated with ICU admission were identified and classified as community-onset, hospital-onset, or ICU-onset if first isolated within, after 48 hours but within 48 hours of ICU admission, or after 48 hours following ICU admission, respectively. Results: We included 3,540 episodes of ICU-associated BSI, with 1,693 classified as community-onset, 663 hospital-onset, and 1,184 ICU-onset. Compared with hospital-onset BSIs, patients with ICU-onset BSIs were younger, had fewer comorbidities, had lower APACHE II scores, and were more likely male. Patients with ICU-onset BSI were more likely to be surgical admissions and have a primary cardiovascular or neurological diagnosis. The distribution of infective agents varied significantly among community-, hospital-, and ICU-onset BSI groups. The all-cause 30-day case-fatality rates for first-episode community-onset, hospital-onset, and ICU-onset BSIs were 17.1%, 21.7%, and 23.5%, respectively ( p < 0.001). Conclusion: With different epidemiological features and causal pathogens, ICU-onset BSI represents a distinct BSI group arising in hospitalized patients.

BACKGROUND:Septic shock is common and associated with significant morbidity and mortality. The ADRENAL trial examined the use of hydrocortisone in patients with septic shock, demonstrating no difference in patient-centred outcomes but a decrease in the time to shock resolution. The change in clinical practice related to the publication of the ADRENAL trial is currently unknown. METHODS:A retrospective cohort study examining the use of hydrocortisone in patients with septic shock was conducted in 12 intensive care units (ICUs). A segmented linear regression was performed to identify a stepwise change in hydrocortisone administration and 90-day mortality associated with the publication of the ADRENAL trial. RESULTS:We included 4,198 patients with a mean age of 58 years (standard deviation, SD17), and the median noradrenaline equivalent score (NEE) was 0.07 μg/kg/min (IQR 0.02-0.17). Segmented regression analysis for hydrocortisone administration identified two breakpoints, 3 months before and 6 months after publication, leading to three periods: Pre-publication, Transition, and Post-publication. Compared to the pre-publication period, the Transition and Post-publication cohorts had a higher proportion of hydrocortisone administration (28% vs. 34% vs. 43%; p < 0.0001). Furthermore, after adjustment for temporal change, the transition period had a significant change in the slope of the proportion of patients receiving hydrocortisone (-0.1% per month vs. +1.4% per month; p = 0.026), whereas this was not statistically significant during the post-publication period (+0.1% per month, p = 0.66). After adjusting for confounders, the Transition and Post-publication periods were independently associated with an increase in hydrocortisone (OR 1.4, 95% CI 1.14-1.77; p = 0.0015 and OR 2.03; 95% CI 1.74-2.36; p < 0.001, respectively). Furthermore, after adjusting for confounders, when compared to the Pre-transition period, the use of hydrocortisone was associated with a statistically significant decrease in 90-day mortality (14% vs. 24% absolute difference, aHR for hydrocortisone effect -0.81; 95% CI 0.65-0.99; p = 0.044). CONCLUSION:Publication of the ADRENAL trial changed clinical practice in Queensland ICUs with increased prescription of hydrocortisone for patients with septic shock with an associated reduction in mortality.

Objective: Knowledge of intensive care unit (ICU) acquired hypernatremia (ICU-AH) has been hampered by the absence of granular data and confounded by variable definitions and inclusion criteria. Design: Multicentre retrospective cohort study. Setting: Twelve ICUs in Queensland (QLD), Australia. Participants: Adult patients admitted to ICU from 2015 to 2021. Only the first ICU admission was considered, and we categorised patients into mild (146-150 mmol center dot L 1 ), moderate (151-155 mmol center dot L 1 ) and severe (>155 mmol center dot L 1 ) ICU-acquired hypernatremia. Main outcome measure: We aimed to study the prevalence of ICU-AH, patient characteristics, trajectory, risk factors, and outcomes. Results: Data from 55,255 ICU admissions were included in the analysis, of which 4146 (7.5 %) patients had ICU-AH. These were subcategorised into mild (n = 2,670, 4.8 %), moderate (n = 1,073, 1.9 %) and severe (n = 403, 0.73 %) forms. Median time to diagnosis was 4 (2-6) d after ICU admission, while median time to peak serum sodium level was 5 (3-8) d. The median maximum sodium level across the cohort was 149 (147-152) mmol center dot L 1 . The sodium correction rate was 1 mmol center dot L 1 per day, taking a median of 3 d (1-5) for sodium levels to return below 145 mmol center dot L 1 . APACHE III score, invasive ventilation, fever, and diuretic use on the day before hypernatremia were independent risk factors for moderate or severe ICU-AH. After adjusting for confounders, all levels of hypernatremia were independently associated with an increased risk of 30-d in-hospital mortality. Conclusions: In a large multicentric study of critically ill patients, ICU-acquired hypernatremia occurred in one in eight admissions after a median of four days in the ICU and was preceded by identifiable and modifiable risk factors. If severe, its correction was slow, and normalisation was delayed. After adjusting for other factors, all levels of hypernatremia were an independent risk factor for 30-d in-hospital mortality. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of College of Intensive Care Medicine of Australia and New Zealand. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).