An exercise in scientific problem-solving: Illustrating the utility of the principles of the Sydney Declaration.

In forensic science, scientific problem-solving is characterized by the recognition of traces as part of iterative reasoning processes to assign meaning to those traces in order to interpret and reconstruct events. Through a set of fundamental principles, the Sydney Declaration presents a foundation of forensic science through the lens of a scientist. The distinction between a scientist and a technician may require clarification-where a prototypical technician follows a prescribed set of 'standard operating procedures' and may be limited in the interpretation of the resultant data, the scientist utilizes knowledge, skills, experience and imagination to identify the issue at hand and develop lines of inquiry for testing and interpretation. This case report draws on the Sydney Declaration in order to highlight the importance of learning about events from careful consideration of both obvious and less obvious traces. A case involving the assault of a police officer is examined to illustrate the use of the Principles: the problem originally defined by investigators at the scene and later by prosecutors resulted in incorrect analysis and interpretation of traces, hampering efforts at an accurate reconstruction of events. This exercise serves to demonstrate that in order to engage in scientific problem-solving, it is necessary to apply observation and reasoning in forensic investigations in order to yield an outcome that can be clearly articulated. The overarching goal is to support the drive to improve forensic science practice, education, and research through a case illustrating the value of the principles of the Sydney Declaration.

Neuroimaging feature extraction using a neural network classifier for imaging genetics.

BACKGROUND: Dealing with the high dimension of both neuroimaging data and genetic data is a difficult problem in the association of genetic data to neuroimaging. In this article, we tackle the latter problem with an eye toward developing solutions that are relevant for disease prediction. Supported by a vast literature on the predictive power of neural networks, our proposed solution uses neural networks to extract from neuroimaging data features that are relevant for predicting Alzheimer's Disease (AD) for subsequent relation to genetics. The neuroimaging-genetic pipeline we propose is comprised of image processing, neuroimaging feature extraction and genetic association steps. We present a neural network classifier for extracting neuroimaging features that are related with the disease. The proposed method is data-driven and requires no expert advice or a priori selection of regions of interest. We further propose a multivariate regression with priors specified in the Bayesian framework that allows for group sparsity at multiple levels including SNPs and genes. RESULTS: We find the features extracted with our proposed method are better predictors of AD than features used previously in the literature suggesting that single nucleotide polymorphisms (SNPs) related to the features extracted by our proposed method are also more relevant for AD. Our neuroimaging-genetic pipeline lead to the identification of some overlapping and more importantly some different SNPs when compared to those identified with previously used features. CONCLUSIONS: The pipeline we propose combines machine learning and statistical methods to benefit from the strong predictive performance of blackbox models to extract relevant features while preserving the interpretation provided by Bayesian models for genetic association. Finally, we argue in favour of using automatic feature extraction, such as the method we propose, in addition to ROI or voxelwise analysis to find potentially novel disease-relevant SNPs that may not be detected when using ROIs or voxels alone.

The use of COVID-19 contact tracing app data as evidence of a crime.

This commentary draws attention to the introduction of data collected by COVID-19 tracing apps as evidence in criminal proceedings and the novel considerations this evidence presents for criminal justice agents and digital forensics professionals.

Consideration of different scoring approaches for a verbal incidental learning measure from the WAIS-IV using hippocampal volumes.

Objective: While Spencer's verbal incidental learning (IL) task-from Vocabulary and Similarities subtests of the WAIS-has been validated relative to traditional memory measures and Alzheimer's disease (AD) pathology, the effectiveness of the particular scoring method used has not been assessed relative to alternative scoring weightings. The purpose of this study was to compare original and alternative scoring methods of this IL task by using an AD biomarker-benchmark to arrive at an optimal approach. Methods: Fifty-five memory-clinic patients aged 59-87 received neuropsychological assessment, measures of IL, and quantitative brain imaging. Partial correlation coefficients with total hippocampal volume-controlling for age, sex, and intracranial volume-were assessed across several IL scoring methods, and partial correlations with measures of memory were examined to evaluate convergent validity.Results: IL scoring methods maximizing the contribution of paired-associate-recall-performance were significantly correlated with both hippocampal volumes and traditional memory measures, whereas discrimination-emphasized scoring methods were not.Conclusions: IL scoring methods emphasizing memory paired-associate recall appeared to be preferable to those emphasizing memory discrimination. Administration of the IL- Similarities subtest alone, without IL- Vocabulary, may strike a balance between strength of relationships with both hippocampal volumes and standard memory measures, while also limiting administration time.

Evaluating the concordance of functional MRI-based language lateralization and Wada testing in epilepsy patients: A single-center analysis.

BACKGROUND: For patients with drug-resistant epilepsy, surgery may be effective in controlling their disease. Surgical evaluation may involve localization of the language areas using functional magnetic resonance imaging (fMRI) or Wada testing. We evaluated the accuracy of task-based fMRI versus Wada-based language lateralization in a cohort of our epilepsy patients. METHODS: In a single-center, retrospective analysis, we identified patients with medically intractable epilepsy who participated in presurgical language mapping (n = 35) with fMRI and Wada testing. Demographic variables and imaging metrics were obtained. We calculated the laterality index (LI) from task-evoked fMRI activation maps across language areas during auditory and reading tasks to determine lateralization. Possible scores for LI range from -1 (strongly left-hemisphere dominant) to 1 (strongly right-hemisphere dominant). Concordance between fMRI and Wada was estimated using Cohen's Kappa coefficient. Association between the LI scores from the auditory and reading tasks was tested using Spearman's rank correlation coefficient. RESULTS: The fMRI-based laterality indices were concordant with results from Wada testing in 91.4% of patients during the reading task (κ = .55) and 96.9% of patients during the auditory task (κ = .79). The mean LIs for the reading and auditory tasks were -0.52 ± 0.43 and -0.68 ± 0.42, respectively. The LI scores for the language and reading tasks were strongly correlated, r(30) = 0.57 (p = 0.001). CONCLUSION: Our findings suggest that fMRI is generally an accurate, low-risk alternative to Wada testing for language lateralization. However, when fMRI indicates atypical language lateralization (e.g., bilateral dominance), patients may benefit from subsequent Wada testing or intraoperative language mapping.

Neuropsychological evaluation in American Sign Language: A case study of a deaf patient with epilepsy.

In high-stake cases (e.g., evaluating surgical candidacy for epilepsy) where neuropsychological evaluation is essential to care, it is important to have culturally and linguistically appropriate and accessible neuropsychological instruments and procedures for use with deaf individuals who use American Sign Language (ASL). Faced with these ethical and professional issues, clinicians may be unable to provide equitable services without consulting with other psychologists and collaborating with the patient and interpreter. This is a case report describing a 43-year-old male with bilateral sensorineural deafness and a lifelong history of drug-resistant temporal lobe epilepsy who presented as a candidate for a comprehensive neurological workup to determine surgical candidacy. He was bilingual (ASL and written English). We describe all aspects of the evaluation, including functional magnetic resonance imaging (fMRI) and Wada testing, using an ASL interpreter. Results from the neuropsychological evaluation were not clearly lateralizing, but suggested greater compromise to the non-dominant right hemisphere. fMRI and Wada test results revealed language and verbal memory functions were lateralized to the left hemisphere. The patient was deemed to be an adequate candidate for surgical resection of portions of the right hemisphere. Comprehensive assessment of neuropsychological functioning in deaf persons who use ASL is feasible. This case report illustrates the important considerations relevant to neuropsychologists providing culturally and linguistically informed assessments to deaf ASL users with epilepsy. Additional research in this area will support future efforts to develop effective and efficient models that could be implemented across different settings. Moreover, clinical guidance is warranted to guide professionals interested in promoting access to high quality neuropsychological services.

An essential role for tungsten in the ecology and evolution of a previously uncultivated lineage of anaerobic, thermophilic Archaea.

Trace metals have been an important ingredient for life throughout Earth's history. Here, we describe the genome-guided cultivation of a member of the elusive archaeal lineage Caldarchaeales (syn. Aigarchaeota), Wolframiiraptor gerlachensis, and its growth dependence on tungsten. A metagenome-assembled genome (MAG) of W. gerlachensis encodes putative tungsten membrane transport systems, as well as pathways for anaerobic oxidation of sugars probably mediated by tungsten-dependent ferredoxin oxidoreductases that are expressed during growth. Catalyzed reporter deposition-fluorescence in-situ hybridization (CARD-FISH) and nanoscale secondary ion mass spectrometry (nanoSIMS) show that W. gerlachensis preferentially assimilates xylose. Phylogenetic analyses of 78 high-quality Wolframiiraptoraceae MAGs from terrestrial and marine hydrothermal systems suggest that tungsten-associated enzymes were present in the last common ancestor of extant Wolframiiraptoraceae. Our observations imply a crucial role for tungsten-dependent metabolism in the origin and evolution of this lineage, and hint at a relic metabolic dependence on this trace metal in early anaerobic thermophiles.

The cost-effectiveness of human papillomavirus vaccination in the Philippines.

Cervical cancer is the second most common cancer among women in the Philippines. Human papillomavirus (HPV) vaccination provides protection from the most common cancer-causing HPV types. This analysis used a proportionate outcomes model to estimate the potential cost-effectiveness of four different HPV vaccine products-Cervarix™, Cecolin®, GARDASIL®, and GARDASIL®9-for routine HPV vaccination of 10 cohorts of 9-year-old girls from the government and societal perspectives. Model parameters included cervical cancer burden, healthcare and program costs, vaccine efficacy with and without potential cross-protection, and vaccination coverage. Univariate and probabilistic sensitivity analyses evaluated the impact of uncertainty on model results. Compared to no vaccination, HPV programs with Cecolin®, Cervarix™, and GARDASIL® are projected to be cost-effective at US$1,210, US$1,300, and US$2,043 per DALY averted, respectively, from the government perspective, and at US$173, US$263, and US$1,006 per DALY averted, respectively, from the societal perspective when cross-protection was considered. When direct comparisons were made across vaccines, GARDASIL® was dominated by Cervarix™ and Cecolin®. In a scenario where cross-protection was not considered, results were similar except that Cervarix™ and GARDASIL® were both dominated by Cecolin®. GARDASIL®9 was not cost-effective under any of the modeled scenarios.

Functional Connectivity Methods and Their Applications in fMRI Data.

The availability of powerful non-invasive neuroimaging techniques has given rise to various studies that aim to map the human brain. These studies focus on not only finding brain activation signatures but also on understanding the overall organization of functional communication in the brain network. Based on the principle that distinct brain regions are functionally connected and continuously share information with each other, various approaches to finding these functional networks have been proposed in the literature. In this paper, we present an overview of the most common methods to estimate and characterize functional connectivity in fMRI data. We illustrate these methodologies with resting-state functional MRI data from the Human Connectome Project, providing details of their implementation and insights on the interpretations of the results. We aim to guide researchers that are new to the field of neuroimaging by providing the necessary tools to estimate and characterize brain circuitry.

A Review of Bayesian Hypothesis Testing and Its Practical Implementations.

We discuss hypothesis testing and compare different theories in light of observed or experimental data as fundamental endeavors in the sciences. Issues associated with the p-value approach and null hypothesis significance testing are reviewed, and the Bayesian alternative based on the Bayes factor is introduced, along with a review of computational methods and sensitivity related to prior distributions. We demonstrate how Bayesian testing can be practically implemented in several examples, such as the t-test, two-sample comparisons, linear mixed models, and Poisson mixed models by using existing software. Caveats and potential problems associated with Bayesian testing are also discussed. We aim to inform researchers in the many fields where Bayesian testing is not in common use of a well-developed alternative to null hypothesis significance testing and to demonstrate its standard implementation.

The Sydney declaration - Revisiting the essence of forensic science through its fundamental principles.

Unlike other more established disciplines, a shared understanding and broad acceptance of the essence of forensic science, its purpose, and fundamental principles are still missing or mis-represented. This foundation has been overlooked, although recognised by many forensic science forefathers and seen as critical to this discipline's advancement. The Sydney Declaration attempts to revisit the essence of forensic science through its foundational basis, beyond organisations, technicalities or protocols. It comprises a definition of forensic science and seven fundamental principles that emphasise the pivotal role of the trace as a vestige, or remnant, of an investigated activity. The Sydney Declaration also discusses critical features framing the forensic scientist's work, such as context, time asymmetry, the continuum of uncertainties, broad scientific knowledge, ethics, critical thinking, and logical reasoning. It is argued that the proposed principles should underpin the practice of forensic science and guide education and research directions. Ultimately, they will benefit forensic science as a whole to be more relevant, effective and reliable.

The trace in the technique: Forensic science and the Connoisseur's gaze.

Both scientific art investigations and forensic investigations rely on observation, inferential reasoning, and analytical techniques to answer questions concerning identification, source, and activity. The forensic scientist and the art connoisseur evaluate the whole-a crime scene or work of art, respectively-and draw meaning from the often-overlooked details, or traces, contained therein. This manuscript considers the correlations between art connoisseurship and forensic science, first by outlining the history of connoisseurship, focusing on the detection and evaluation of traces through patient observation, reasoning, and comparison based on methods established by Giovanni Morelli in the nineteenth century. This article then explores connoisseurship and forensic science within the historical sciences framework, based on the process in which observable traces can be ordered to provide a reconstruction of unobservable past events. Finally, this article asserts that art can be used to shape and refine the scientist's practiced eye, thereby improving trace detection and interpretation in investigations.

Predicting Upcoming Events Occurring in the Space Surrounding the Hand.

Predicting upcoming sensorimotor events means creating forward estimates of the body and the surrounding world. This ability is a fundamental aspect of skilled motor behavior and requires an accurate and constantly updated representation of the body and the environment. To test whether these prediction mechanisms could be affected by a peripheral injury, we employed an action observation and electroencephalogram (EEG) paradigm to assess the occurrence of prediction markers in anticipation of observed sensorimotor events in healthy and brachial plexus injury (BPI) participants. Nine healthy subjects and six BPI patients watched a series of video clips showing an actor's hand and a colored ball in an egocentric perspective. The color of the ball indicated whether the hand would grasp it (hand movement), or the ball would roll toward the hand and touch it (ball movement), or no event would occur (no movement). In healthy participants, we expected to find distinct electroencephalographic activation patterns (EEG signatures) specific to the prediction of the occurrence of each of these situations. Cluster analysis from EEG signals recorded from electrodes placed over the sensorimotor cortex of control participants showed that predicting either an upcoming hand movement or the occurrence of a tactile event yielded specific neural signatures. In BPI participants, the EEG signals from the sensorimotor cortex contralateral to the dominant hand in the hand movement condition were different compared to the other conditions. Furthermore, there were no differences between ball movement and no movement conditions in the sensorimotor cortex contralateral to the dominant hand, suggesting that BPI blurred specifically the ability to predict upcoming tactile events for the dominant hand. These results highlight the role of the sensorimotor cortex in creating estimates of both actions and tactile interactions in the space around the body and suggest plastic effects on prediction coding following peripheral sensorimotor loss.

Teleneuropsychology for Monolingual and Bilingual Spanish-Speaking Adults in the Time of COVID-19: Rationale, Professional Considerations, and Resources.

OBJECTIVE: Neuropsychological assessments with monolingual Spanish and bilingual Spanish/English-speaking adults present unique challenges. Barriers include, but are not limited to, the paucity of test norms, uncertainty about the equivalence of translated neuropsychological tests, and limited proficiency in the provision of culturally competent services. Similar issues generalize to telephone- and video-based administration of neuropsychological tests or teleneuropsychology (TeleNP) with Hispanics/Latinos (as), and few studies have examined its feasibility and validity in this group. The sudden onset of the COVID-19 pandemic prompted neuropsychologists to identify alternative ways to provide equitable care. Clinicians providing TeleNP to this population during (and after) the pandemic must consider safety, professional factors, and systemic barriers to accessing and benefitting from virtual modalities. METHOD: This clinical process manuscript describes how cross-cultural neuropsychologists across five U.S. academic institutions serving Hispanics/Latinos (as) developed TeleNP models of care during the pandemic. RESULTS: Workflows, test batteries, and resources for TeleNP assessment with monolingual and bilingual Spanish-speaking patients are included. Factors guiding model development and informing decisions to incorporate virtual administration of neuropsychological tests into their practice are also discussed. CONCLUSIONS: Provision of TeleNP is a promising modality. Additional research in this area is warranted with focus on cultural and contextual factors that support or limit the use of TeleNP with this community.

Acute Stress Increases Intraocular Pressure in Nonhuman Primates.

Purpose: To quantify intraocular pressure (IOP) change and time course during stressful activity. Study Design: Experimental Study. Subjects: Three nonhuman primates (NHPs). Methods: Bilateral IOP and aortic blood pressure (BP) were recorded continuously, then averaged for periods of 8-30 seconds before, during, and after a common anesthetic induction procedure (cage squeeze followed by intramuscular injection). Experiments were repeated four times in each NHP. Main Outcome Measures: IOP, BP, and heart rate (HR) change during an anesthetic induction procedure. Results: IOP, mean arterial pressure (MAP), and HR increased rapidly and significantly by 27%, 38%, 34%, respectively, in anticipation of anesthetic induction (Figure; p<0.05). IOP rose ~10% within 10 seconds of hearing the technician enter the outer anteroom door, and reached its maximum within ~1 minute of first anticipating human contact. IOP fell to below baseline levels within 1 minute after anesthetic induction. Conclusions: IOP increases rapidly and significantly in response to stressful situations in the nonhuman primate.

Bayesian Semiparametric Functional Mixed Models for Serially Correlated Functional Data, with Application to Glaucoma Data.

Glaucoma, a leading cause of blindness, is characterized by optic nerve damage related to intraocular pressure (IOP), but its full etiology is unknown. Researchers at UAB have devised a custom device to measure scleral strain continuously around the eye under fixed levels of IOP, which here is used to assess how strain varies around the posterior pole, with IOP, and across glaucoma risk factors such as age. The hypothesis is that scleral strain decreases with age, which could alter biomechanics of the optic nerve head and cause damage that could eventually lead to glaucoma. To evaluate this hypothesis, we adapted Bayesian Functional Mixed Models to model these complex data consisting of correlated functions on spherical scleral surface, with nonparametric age effects allowed to vary in magnitude and smoothness across the scleral surface, multi-level random effect functions to capture within-subject correlation, and functional growth curve terms to capture serial correlation across IOPs that can vary around the scleral surface. Our method yields fully Bayesian inference on the scleral surface or any aggregation or transformation thereof, and reveals interesting insights into the biomechanical etiology of glaucoma. The general modeling framework described is very flexible and applicable to many complex, high-dimensional functional data.

Sleep quality mediates the relationship between frailty and cognitive dysfunction in non-demented middle aged to older adults.

ABSTRACTObjectives:Frailty is associated with cognitive decline in older adults. However, the mechanisms explaining this relationship are poorly understood. We hypothesized that sleep quality may mediate the relationship between frailty and cognition. PARTICIPANTS: 154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included. MEASUREMENTS: Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures. RESULTS: Frailty severity predicted weaker executive function (B = -2.77, ß = -0.30, 95% CI = -4.05 - -1.29) and processing speed (B = -1.57, ß = -0.17, 95% CI = -3.10 - -0.16). Poor sleep quality predicted poorer executive function (B = -0.47, ß = -0.21, 95% CI = -0.79 - -0.08), processing speed (B = -0.64, ß = -0.28, 95% CI = -0.98 - -0.31), learning (B = -0.42, ß = -0.19, 95% CI = -0.76 - -0.05) and delayed recall (B = -0.41, ß = -0.16, 95% CI = -0.80 - -0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = -0.66, ß = -0.07, 95% CI = -1.48 - -0.39), learning (B = -0.85, ß = -0.07, 95% CI = -1.85 - -0.12), delayed recall (B = -0.47, ß = -0.08, 95% CI = -2.12 - -0.39) and processing speed (B = -0.90, ß = -0.09, 95% CI = -1.85 - -0.20). CONCLUSIONS: Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.