Entering the Era of Data Science: Targeted Learning and the Integration of Statistics and Computational Data Analysis

This outlook article will appear in Advances in Statistics and it reviews the research of Dr. van der Laan\u27s group on Targeted Learning, a subfield of statistics that is concerned with the construction of data adaptive estimators of user-supplied target parameters of the probability distribution of the data and corresponding confidence intervals, aiming to only rely on realistic statistical assumptions. Targeted Learning fully utilizes the state of the art in machine learning tools, while still preserving the important identity of statistics as a field that is concerned with both accurate estimation of the true target parameter value and assessment of uncertainty in order to make sound statistical conclusions. We also provide a philosophical historical perspective on Targeted Learning, also relating it to the new developments in Big Data. We conclude with some remarks explaining the immediate relevance of Targeted Learning to the current big data movement

Targeted Learning for Causality and Statistical Analysis in Medical Research

The authors present the use of targeted learning methods for medical research, prepared as a chapter for the upcoming book Statistics: Discovering Your Future Power. The targeted learning framework involves the explicit specification of the data, model, and parameter. The estimators are double robust and efficient, and can incorporate machine learning procedures such as the super learner

A new physiological model for studying the effect of chest compression and ventilation during cardiopulmonary resuscitation: The Thiel cadaver

BACKGROUND: Studying ventilation and intrathoracic pressure (ITP) induced by chest compressions (CC) during Cardio Pulmonary Resuscitation is challenging and important aspects such as airway closure have been mostly ignored. We hypothesized that Thiel Embalmed Cadavers could constitute an appropriate model. METHODS: We assessed respiratory mechanics and ITP during CC in 11 cadavers, and we compared it to measurements obtained in 9 out-of-hospital cardiac arrest patients and to predicted values from a bench model. An oesophageal catheter was inserted to assess chest wall compliance, and ITP variation (ΔITP). Airway pressure variation (ΔPaw) at airway opening and ΔITP generated by CC were measured at decremental positive end expiratory pressure (PEEP) to test its impact on flow and ΔPaw. The patient\u27s data were derived from flow and airway pressure captured via the ventilator during resuscitation. RESULTS: Resistance and Compliance of the respiratory system were comparable to those of the out-of-hospital cardiac arrest patients (C 42 ± 12 vs C 37.3 ± 10.9 mL/cmHO and Res 17.5 ± 7.5 vs Res 20.2 ± 5.3 cmHO/L/sec), and remained stable over time. During CC, ΔITP varied from 32 ± 12 cmHO to 69 ± 14 cmHO with manual and automatic CC respectively. Transmission of ΔITP at the airway opening was significantly affected by PEEP, suggesting dynamic small airway closure at low lung volumes. This phenomenon was similarly observed in patients. CONCLUSION: Respiratory mechanics and dynamic pressures during CC of cadavers behave as predicted by a theoretical model and similarly to patients. The Thiel model is a suitable to assess ITP variations induced by ventilation during CC

Toward complete oral cavity cancer resection using a handheld diffuse reflectance spectroscopy probe

This ex-vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy tissue, with the aim to develop a technology that can assess resection margins for the presence of tumor cells during oral cavity cancer surgery. Diffuse reflectance spectra were acquired on fresh surgical specimens from 28 patients with oral cavity squamous cell carcinoma. The spectra (400 to 1600 nm) were detected after illuminating tissue with a source fiber at 0.3-, 0.7-, 1.0-, and 2.0-mm distances from a detection fiber, obtaining spectral information from different sampling depths. The spectra were correlated with histopathology. A total of 76 spectra were obtained from tumor tissue and 110 spectra from healthy muscle tissue. The first- A nd second-order derivatives of the spectra were calculated and a classification algorithm was developed using fivefold cross validation with a linear support vector machine. The best results were obtained by the reflectance measured with a 1-mm source-detector distance (sensitivity, specificity, and accuracy are 89%, 82%, and 86%, respectively). DRS can accurately discriminate tumor from healthy tissue in an ex-vivo setting using a 1-mm source-detector distance. Accurate validation methods are warranted for larger sampling depths to allow for guidance during oral cavity cancer excision.</p

Rapid pre-eruptive mush reorganisation and atmospheric volatile emissions from the 12.9 ka Laacher See eruption, determined using apatite

Magma is commonly thought to be stored as a crystal-rich mush within vertically extensive, crustal storage regions. A key unknown is how to remobilise and erupt such crystal-rich material, and whether the growth of gas bubbles within the mush could promote remobilisation. In order to investigate this, we need improved constraints on the timing of volatile saturation in magmas. The mineral apatite represents a potentially useful record of pre-eruptive magmatic volatiles, but data interpretation is complex because exchange reactions control the volatile partitioning. Model solutions are therefore non-unique. Here, we present a numerical forward modelling program with a sensitivity analysis function, which addresses non-uniqueness by identifying alternative sets of starting parameters that match a target compositional trend through a population of apatite crystals. The model is applied to a new dataset of volatiles in apatite from the 12.9 ka Laacher See eruption, Eifel volcanic region, Germany. The results indicate that the magma was initially strongly volatile-undersaturated and became saturated through progressive crystal fractionation. Apatite crystals are not in volatile or trace element equilibrium with their carrier melts, indicating dispersal of crystals into different chemical environments. Consideration of apatite diffusivities suggests that this reorganisation occurred shortly before eruption. Our modelling results also allow us to constrain directly the amount of pre-eruptive magmatic vapour emitted during the explosive eruption, highlighting the importance of considering the behaviour of halogens during magma storage. Overall, our approach confirms the value of measuring apatite volatile contents and highlights the potential of this method to provide quantitative constraints on magmatic evolution and storage conditions

Potentially harmful effects of inspiratory synchronization during pressure preset ventilation

Purpose: Pressure preset ventilation (PPV) modes with set inspiratory time can be classified according to their ability to synchronize pressure delivery with patient's inspiratory efforts (i-synchronization). Non-i-synchronized (like airway pressure release ventilation, APRV), partially i-synchronized (like biphasic airway pressure), and fully i-synchronized modes (like assist-pressure control) can be distinguished. Under identical ventilatory settings across PPV modes, the degree of i-synchronization may affect tidal volume (V T), transpulmonary pressure (P TP), and their variability. We performed bench and clinical studies. Methods: In the bench study, all the PPV modes of five ventilators were tested with an active lung simulator. Spontaneous efforts of -10 cmH2O at rates of 20 and 30 breaths/min were simulated. Ventilator settings were high pressure 30 cmH2O, positive end-expiratory pressure (PEEP) 15 cmH2O, frequency 15 breaths/min, and inspiratory to expiratory ratios (I:E) 1:3 and 3:1. In the clinical studies, data from eight intubated patients suffering from acute respiratory distress syndrome (ARDS) and ventilated with APRV were compared to the bench tests. In four additional ARDS patients, each of the PPV modes was compared. Results: As the degree of i-synchronization among the different PPV modes increased, mean V T and P TP swings markedly increased while breathing variability decreased. This was consistent with clinical comparison in four ARDS patients. Observational results in eight ARDS patients show low V T and a high variability with APRV. Conclusion: Despite identical ventilator settings, the different PPV modes lead to substantial differences in V T, P TP, and breathing variability in the presence spontaneous efforts. Clinicians should be aware of the possible harmful effects of i-synchronization especially when high V T is undesirable

Effect of different seated positions on lung volume and oxygenation in acute respiratory distress syndrome

RATIONALE: Lung volume available for ventilation is markedly decreased during acute respiratory distress syndrome. Body positioning may contribute to increase lung volume and partial verticalization is simple to perform. This study evaluated whether verticalization had parallel effects on oxygenation and end expiratory lung volume (EELV). METHODS: Prospective multicenter study in 40 mechanically ventilated patients with ALI/ARDS in five university hospital MICUs. We evaluated four 45-min successive trunk position epochs (supine slightly elevated at 15\ub0; semi recumbent with trunk elevated at 45\ub0; seated with trunk elevated at 60\ub0 and legs down at 45\ub0; back to supine). Arterial blood gases, EELV measured using the nitrogen washin/washout, and static compliance were measured. Responders were defined by a PaO\u2082/FiO\u2082 increase >20 % between supine and seated position. Results are median [25th-75th percentiles]. RESULTS: With median PEEP = 10 cmH\u2082O, verticalization increased lung volume but only responders (13 patients, 32 %) had a significant increase in EELV/PBW (predicted body weight) compared to baseline. This increase persisted at least partially when patients were positioned back to supine. Responders had a lower EELV/PBW supine [14 mL/kg (13-15) vs. 18 mL/kg (15-27) (p = 0.005)] and a lower compliance [30 mL/cmH\u2082O (22-38) vs. 42 (30-46) (p = 0.01)] than non-responders. Strain decreased with verticalization for responders. EELV/PBW increase and PaO\u2082/FiO\u2082 increase were not correlated. DISCUSSION: Verticalization is easily achieved and improves oxygenation in approximately 32 % of the patients together with an increase in EELV. Nonetheless, effect of verticalization on EELV/PBW is not predictable by PaO\u2082/FiO\u2082 increase, its monitoring may be helpful for strain optimiz

Toward complete oral cavity cancer resection using a handheld diffuse reflectance spectroscopy probe

This ex-vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy tissue, with the aim to develop a technology that can assess resection margins for the presence of tumor cells during oral cavity cancer surgery. Diffuse reflectance spectra were acquired on fresh surgical specimens from 28 patients with oral cavity squamous cell carcinoma. The spectra (400 to 1600 nm) were detected after illuminating tissue with a source fiber at 0.3-, 0.7-, 1.0-, and 2.0-mm distances from a detection fiber, obtaining spectral information from different sampling depths. The spectra were correlated with histopathology. A total of 76 spectra were obtained from tumor tissue and 110 spectra from healthy muscle tissue. The first- and second-order derivatives of the spectra were calculated and a classification algorithm was developed using fivefold cross validation with a linear support vector machine. The best results were obtained by the reflectance measured with a 1-mm source-detector distance (sensitivity, specificity, and accuracy are 89%, 82%, and 86%, respectively). DRS can accurately discriminate tumor from healthy tissue in an ex-vivo setting using a 1-mm source-detector distance. Accurate validation methods are warranted for larger sampling depths to allow for guidance during oral cavity cancer excision.Medical Instruments & Bio-Inspired Technolog

Intrathoracic Airway Closure Impacts CO 2 Signal and Delivered Ventilation during Cardiopulmonary Resuscitation

International audienc