Next-generation time of death estimation: combining surrogate model-based parameter optimization and numerical thermodynamics.

The postmortem interval (PMI), i.e. the time since death, plays a key role in forensic investigations, as it aids in the reconstruction of the timeline of events.

Individualised and non-contact post-mortem interval determination of human bodies using visible and thermal 3D imaging.

Determining the time since death, i.e., post-mortem interval (PMI), often plays a key role in forensic investigations.

The abscopal effect of radiation therapy.

Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells.

Current Ovarian Cancer Maintenance Strategies and Promising New Developments.

While ovarian cancer typically responds well to front line treatment, many patients will relapse within 5 years. Treatment options are less effective at each recurrence highlighting the need for novel maintenance therapies. PolyADP-ribose polymerase (PARP) inhibitors have recently gained approval in ovarian cancer maintenance.

FDA efficiency for approval process of COVID-19 therapeutics.

Coronavirus disease 19 (COVID-19) is an infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The pandemic spread of SARS-CoV-2 has resulted in significant health, economic, and social ramifications. There are no U.

Resident Memory T Cells and Their Effect on Cancer.

Resident memory T (T) cells are a unique subset of CD8 T cells that are present within certain tissues and do not recirculate through the blood. Long term memory establishment and maintenance are dependent on tissue population of memory T cells. They are characterized by dual CD69/CD103 positivity, and play a role in both response to viral infection and local cancer immunosurveillance.

Relationship of hypothyroidism and immune response to pegylated IL-10/nivolumab.

We describe a case of an advanced disease non-small-cell lung cancer patient with low PD-L1 expression, but high tumor mutation burden (35 muts/Mb) who developed immune-related hypothyroidism and achieved subsequent partial response, while on clinical trial (NCT03382912) with nivolumab and PEGylated IL-10 (Pegilodecakin, ARMO BioSciences/Eli Lilly and Company, IN, USA). Results suggest positive antitumor activity to combination IL-10/nivolumab despite low PD-L1 expression but in likely relationship to high tumor mutation burden and in association with immune-mediated thyroid dysfunction in this case.

Reconstructing the time since death using noninvasive thermometry and numerical analysis.

The early postmortem interval (PMI), i.e., the time shortly after death, can aid in the temporal reconstruction of a suspected crime and therefore provides crucial information in forensic investigations.

Feasibility of Full Neuromuscular Blockade During Transcranial Motor Evoked Potential Monitoring of Neurosurgical Procedures.

Background: Transcranial motor evoked potential (TcMEP) monitoring is conventionally performed during surgical procedures without or with minimal neuromuscular blockade (NMB) because of its potential interference with signal interpretation. However, full blockade offers increased anesthetic management options and facilitates surgery. Here, the feasibility of TcMEP interpretation was assessed during full NMB in adult neurosurgical patients.

TMB: a promising immune-response biomarker, and potential spearhead in advancing targeted therapy trials.

Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, we review checkpoint inhibitor signal pathways, resistance and sensitivity mechanisms, as well as response rates.

Society for Neuroscience in Anesthesiology & Critical Care (SNACC) Neuroanesthesiology Education Milestones for Resident Education.

Background: The Accreditation Council for Graduate Medical Education (ACGME) has introduced competency-based assessments (milestones) for resident education. However, the existing milestones for Anesthesiology are not specific to Neuroanesthesiology. The Society for Neuroscience in Anesthesiology & Critical Care (SNACC) commissioned a task force to adapt the ACGME anesthesiology milestones for use in Neuroanesthesiology training, and to provide recommendations for implementing milestones.

Photogrammetry using visible, infrared, hyperspectral and thermal imaging of crime scenes.

Photogrammetry is a method for obtaining virtual 3D models of objects and scenes. The technique is increasingly used to record the crime scene in its original, undisturbed state for mapping, analytical and reconstruction purposes. Recently, it was shown that it is possible to visualize and/or chemically analyze latent traces by using advanced cameras which either operate in wavelength ranges beyond the visible range, and/or are able to obtain spectrally resolved images.

Fully Water-Soluble, High-Performance Transient Sensors on a Versatile Galactomannan Substrate Derived from the Endosperm.

Green electronics on biodegradable substrates from natural sources have gained broad interest because of the advantages of being biodegradable, recyclable, sustainable, and cost-efficient. This study presents a low-cost, yet simple extraction and purification method that explores aqueous extraction and precipitation with ethanol for the synthesis of galactomannan films. In salient contrast to the other materials of natural origin, the process to obtain galactomannan films is energy efficient and environmentally friendly.

Phase I Trial of a Tablet Formulation of Pilaralisib, a Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors.

Lessons Learned: A phase I study of the pan-class I phosphoinositide 3-kinase inhibitor pilaralisib (in capsule formulation) in advanced solid tumors established the maximum tolerated dose as 600 mg once daily.The current study investigated pilaralisib in tablet formulation.Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity.

Visual characteristics for sequencing of overlapping bloodstain patterns.

The deposition sequence of overlapping bloodstain patterns can be valuable reconstructive information. A formal method for sequencing overlapping bloodstain patterns has yet to be published. We present a method for sequencing overlapping transfer and drip stains using visual characteristics.

Large area imaging of forensic evidence with MA-XRF.

This study introduces the use of macroscopic X-ray fluorescence (MA-XRF) for the detection, classification and imaging of forensic traces over large object areas such as entire pieces of clothing and wall paneling. MA-XRF was sufficiently sensitive and selective to detect human biological traces like blood, semen, saliva, sweat and urine on fabric on the basis of Fe, Zn, K, Cl and Ca elemental signatures. With MA-XRF a new chemical contrast is introduced for human stain detection and this can provide a valuable alternative when the evidence item is challenging for conventional techniques.

A phase I dose-escalation study of the safety and pharmacokinetics of a tablet formulation of voxtalisib, a phosphoinositide 3-kinase inhibitor, in patients with solid tumors.

Background Voxtalisib, a PI3K/mTOR inhibitor, has shown antitumor activity in capsule formulation in patients with solid tumors. This Phase I study assessed safety and pharmacokinetics of voxtalisib administered as immediate-release tablets in patients with solid tumors (NCT01596270). Methods A "3 + 3" dose escalation design was used.

Spontaneous emergence of fast attractor dynamics in a model of developing primary visual cortex.

Recent evidence suggests that neurons in primary sensory cortex arrange into competitive groups, representing stimuli by their joint activity rather than as independent feature analysers. A possible explanation for these results is that sensory cortex implements attractor dynamics, although this proposal remains controversial. Here we report that fast attractor dynamics emerge naturally in a computational model of a patch of primary visual cortex endowed with realistic plasticity (at both feedforward and lateral synapses) and mutual inhibition.

Imagery May Arise from Associations Formed through Sensory Experience: A Network of Spiking Neurons Controlling a Robot Learns Visual Sequences in Order to Perform a Mental Rotation Task.

Mental imagery occurs "when a representation of the type created during the initial phases of perception is present but the stimulus is not actually being perceived." How does the capability to perform mental imagery arise? Extending the idea that imagery arises from learned associations, we propose that mental rotation, a specific form of imagery, could arise through the mechanism of sequence learning-that is, by learning to regenerate the sequence of mental images perceived while passively observing a rotating object. To demonstrate the feasibility of this proposal, we constructed a simulated nervous system and embedded it within a behaving humanoid robot.

Medical Care for Swimmers.

Swimming is one of the most popular sports worldwide. Competitive swimming is one of the most watched sports during the Olympic Games. Swimming has unique medical challenges as a result of a variety of environmental and chemical exposures.

Phase I study of XL281 (BMS-908662), a potent oral RAF kinase inhibitor, in patients with advanced solid tumors.

Background XL281 is a potent and selective inhibitor of wild-type and mutant RAF kinases with anti-tumor activity in multiple xenograft models. Mutations in KRAS or BRAF can activate the RAF/MEK/ERK pathway in human tumors and may confer sensitivity to RAF kinase inhibitors. Methods We performed a phase I study of XL281 in patients with advanced solid tumors.

Visualization of latent blood stains using visible reflectance hyperspectral imaging and chemometrics.

The detection of latent traces is an important aspect of crime scene investigation. Blood stains on black backgrounds can be visualized using chemiluminescence, which is invasive and requires a darkened room, or near-infrared photography, for which investigators need to change filters manually to optimize contrast. We demonstrated the performance of visible reflectance hyperspectral imaging (400-720 nm) for this purpose.

Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245408 (XL147), an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors.

Purpose: SAR245408 is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. This phase I study determined the maximum tolerated dose (MTD) of two dosing schedules [first 21 days of a 28-day period (21/7) and continuous once-daily dosing (CDD)], pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy.

Experimental Design: Patients with refractory advanced solid malignancies were treated with SAR245408 using a 3 + 3 design.