Suicide methods and severe mental illness: A systematic review and meta-analysis.

INTRODUCTION: People with severe mental illness (SMI) have a higher risk of suicide compared with the general population. However, variations in suicide methods between people with different SMIs have not been examined. The aim of this pre-registered (PROSPERO CRD42022351748) systematic review was to pool the odds of people with SMI who die by suicide versus those with no SMI, stratified by suicide method. METHODS: Searches were conducted on December 11, 2023 across PubMed, PsycInfo, CINAHL, and Embase. Eligible studies were those that reported suicide deaths stratified by SMI and suicide methods. Studies were pooled in a random-effects meta-analysis, and risk of bias was measured by the Joanna Briggs Institute checklist. RESULTS: After screening, 12 studies were eligible (n = 380,523). Compared with those with no SMI, people with schizophrenia had 3.38× higher odds of jumping from heights (95% CI: 2.08-5.50), 1.93× higher odds of drowning (95% CI: 1.50-2.48). People with bipolar disorder also had 3.2× higher odds of jumping from heights (95% CI: 2.70-3.78). Finally, people with major depression had 3.11× higher odds of drug overdose (95% CI: 1.53-6.31), 2.11× higher odds of jumping from heights (95% CI: 1.93-2.31), and 2.33× lower odds of dying by firearms (OR = 0.43, 95% CI: 0.33-0.56). No studies were classified as high risk of bias, and no outcomes had high levels of imprecision or indirectness. CONCLUSION: These findings could inform lethal means counselling practices in this population. Additionally individual, clinical, community and public health interventions for people with SMI should prioritise, where feasible, means restriction including access to heights or drugs to overdose.

Improving heart rate monitoring in the obese with time-of-flight photoplethysmography (TOF-PPG): a quantitative analysis of source-detector-distance effect.

Commercial photoplethysmography (PPG) sensors rely on the measurement of continuous-wave diffuse reflection signals (CW-DRS) to monitor heart rate. Using Monte Carlo modeling of light propagation in skin, we quantitatively evaluate the dependence of continuous-wave photoplethysmography (CW-PPG) in commercial wearables on source-detector distance (SDD). Specifically, when SDD increases from 0.5 mm to 3.3 mm, CW-PPG signal increases by roughly 846% for non-obese (NOB) skin and roughly 683% for morbidly obese (MOB) skin. Ultimately, we introduce the concept of time-of-flight PPG (TOF-PPG) which can significantly improve heart rate signals. Our model shows that the optimized TOF-PPG improves heart rate monitoring experiences by roughly 47.9% in NOB and 93.2% in MOB when SDD = 3.3 mm is at green light. Moving forward, these results will provide a valuable source for hypothesis generation in the scientific community to improve heart rate monitoring.

Enhancing classical swine fever virus identification: the advantages of Field-LAMP testing.

Classical swine fever virus (CSFV) identification has witnessed significant advancements with the development of rapid reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays. However, conventional RT-LAMP assays for CSFV diagnosis are hindered by a laborious RNA extraction step. Moreover, the need for thermal incubators and expensive micropipettes has limited their application in field settings. Addressing these challenges, our study presents a groundbreaking solution-an electro-free and point-of-care (POC) tool known as the field-LAMP assay-for the rapid clinical detection of CSFV. By eliminating the RNA extraction requirement, advancing the colorimetric read-out and lyophilized reaction reagents, our field-LAMP assay streamlines the diagnostic process, saving valuable time and effort. This novel approach also overcomes the dependency on electric-dependent thermal incubators and expensive micropipettes, making it practical and accessible for use in the field. The successful development of the field-LAMP assay marks a significant milestone in CSFV detection. This electro-free and POC tool offers several advantages, including its ability to deliver rapid results without compromising accuracy, facilitating prompt response and containment measures.

Assessment of bowel movement dysfunction following laparoscopic low anterior resection for rectal cancer: a single-center study from Vietnam.

OBJECTIVE: Postoperative bowel movement dysfunction is a challenging problem greatly affecting patients' quality of life after low anterior resection. We aimed to evaluate the bowel movement function of patients undergoing laparoscopic low anterior resection for rectal cancer. PATIENTS AND METHODS: This retrospective study recruited 82 rectal cancer patients undergoing laparoscopic low anterior resection from July 2018 to July 2020 at 108 Military Central Hospital, Hanoi, Vietnam. RESULTS: The patients' mean age was 62.3±11.6 (28-84) years, 54 (65.9%) were males, and 28 (34.1%) were females. Bowel movement function changed significantly after one year: the average score for low anterior resection syndrome (LARS) after three months, six months, and one year was 17.6, 14.0, and 10.6, respectively. The rate of patients with major LARS decreased from 26.8% after three months to 14.6% after one year. The Wexner score also decreased from 5.9 after three months to 3.4 after one year. The rate of patients with normal bowel movement increased from 28.0% after three months to 46.3% after one year. The rate of patients with complete fecal incontinence decreased from 11.0% after three months to 7.3% after one year. Preoperative chemoradiotherapy (p=0.017), tumor location (p=0.02), method of anastomosis (p=0.01), and anastomosis location (p=0.000) were risk factors associated with major LARS after surgery. CONCLUSIONS: Bowel movement dysfunction in rectal cancer patients undergoing laparoscopic low anterior resection is a common and persistent problem after surgery. However, bowel function gradually recovers over time. Therefore, patients should be monitored and supported for a better quality of life.

[Analysis of the results of modified personalized topographically and tomographically oriented technique of ultraviolet corneal collagen crosslinking]. / Analiz rezul'tatov modifitsirovannoi personalizirovannoi topograficheski i tomograficheski orientirovannoi metodiki ul'trafioletovogo krosslinkinga rogovichnogo kollagena.

PURPOSE: The study aims to develop a modified personalized topographically and tomographically oriented technique of ultraviolet corneal collagen cross-linking (UVCXL) to affect the area of the cornea with weakest biomechanical properties as determined by mathematical modeling. MATERIAL AND METHODS: Modeling of the biomechanics of keratoconic cornea under conditions of external diagnostic action was done using COMSOL Multiphysics® software. Finite-element analysis procured 3D images of stress/deformation distribution pattern throughout the cornea. Matching these 3D images with primary topographic and tomographic Pentacam AXL maps and Corvis ST findings allowed determining localization and dimensions of impaired regions of the cornea. The acquired data helped develop the modified corneal collagen cross-linking technique, which was applied in the treatment of 36 persons (36 eyes) with degrees I and II keratoconus. RESULTS: Uncorrected and best-corrected visual acuity (UCVA and BCVA logMAR) in all patients after modified UVCXL increased after the follow-up period lasting 6-12 months by 0.2±0.19 (23%) and 0.1±0.14 (29%) (p<0.05), respectively, in comparison with preoperative values. Maximum keratometry (Kmax) decreased by 1.35±1.63% (3%; p<0.05) in all cases at 6-12 months follow-up. Improvement of corneal biomechanical strength was determined by statistically significant increase in corneal stiffness index (SP-A1) and corneal stress-strain index (SSI) measured with Pentacam AXL and Corvis ST at 6-12 months follow-up by 15.1±5.04 (18%) and 0.21±0.20 (23%) (p<0.05), respectively. Effectiveness of the developed UVCXL technique is also confirmed by the appearance of a characteristic morphological marker - «demarcation line¼ at the cross-linking site in keratoconus projection at the depth of 240±10.2 µm. CONCLUSION: The developed personalized topographically and tomographically oriented UVCXL technique provides an evident stabilizing effect on the cornea in the form of an increase in its biomechanical strength, improvement of clinical, functional indicators and safety of keratoconus treatment.

Mechanistic insights into efficient peroxymonosulfate activation by NiCo layered double hydroxides.

The efficient removal of organic refractory pollutants such as dyes and antibiotics in wastewater is crucial for protecting the environment and human health. In this work, a NiCo-layered double hydroxide (NiCo-LDH) with a uniform microspherical, hierarchical structure and a high surface area was successfully synthesized as an effective peroxymonosulfate (PMS) activator for the degradation of various organic dyes and antibiotics. The influence of various parameters on the catalytic activity of the NiCo-LDH was determined. Radical scavenger studies unveiled the major reactive oxygen species (ROSs) generated in the NiCo-LDH/PSM system to be 1O2, SO4•-, and O2•-. Ex-situ X-ray photoelectron spectroscopy (XPS) analysis uncovered the role of Co sites and oxygen vacancy as active sites and revealed the reversible redox properties of NiCo-LDH based on Co2+/Co3+ cycles. The activation mechanism and Rhodamine B (RhB) degradation pathways were experimentally studied and proposed. The NiCo-LDH is highly versatile, reusable and stable as shown by post-catalysis characterizations. This work shows the excellent catalysis performances and provides insights into the activation mechanism of PMS by NiCo-LDH for organic pollutant remediation.

Neural underpinnings of expecting alcohol: Placebo alcohol administration alters nucleus accumbens resting state functional connectivity.

BACKGROUND: Using balanced placebo designs, seminal alcohol administration research has shown individuals' beliefs about whether they have consumed alcohol, irrespective of the actual presence of alcohol, can determine level of alcohol consumption and impact social behavior. Despite the known effect of expecting alcohol on drinking behavior, few studies have used the placebo manipulation to directly investigate the neural underpinnings of the expectancy-related effects that occur following perceived alcohol consumption in humans. The present paper examined placebo responses in the laboratory to better understand the neural basis for the psychological phenomenon of expectancies. METHODS: As part of a larger within-subjects study design, healthy young adults (N = 22, agemean+SD=23 +1) completed resting state fMRI scans and measures of subjective response before and after consuming placebo beverages. Effect of placebo beverage consumption (pre- versus post-beverage consumption) on functional connectivity within prefrontal cortical networks was examined using the CONN Toolbox. Relations between perceived subjective response to alcohol with functional connectivity response following placebo beverage consumption were examined. RESULTS: Compared to pre-beverage scan, placebo beverage consumption was associated with increased positive functional connectivity between right nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex (pFDR<0.05). Subjective ratings of intoxication (i.e., feeling 'drunk') positively correlated with placebo beverage-related increases in nucleus accumbens - subcallosal cingulate cortex functional connectivity. CONCLUSION: Results suggest placebo response to alcohol is associated with increased functional connectivity within a key reward network (nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex) and put forth a mechanism by which alcohol expectancies may contribute to the subjective experience of intoxication.

Diagnostic value of cerebral vasospasm by transcranial doppler ultrasound in Vietnamese patients with subarachnoid hemorrhage.

OBJECTIVE: Although the application of transcranial Doppler (TCD) ultrasonography in clinical diagnosis of cerebral vasospasm is popular in clinical practice in Vietnam, available evidence of the predictive value of vasospasm on TCD in the literature was mostly reported from large institutions in developed countries. Hence, this study was conducted to evaluate the value of TCD ultrasonography in the diagnosis of vasospasm in patients with subarachnoid hemorrhage (SAH) in Vietnam. PATIENTS AND METHODS: This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between 2008 and December 2011. TCD and 64-slice computed tomographic angiography (CTA) were used to cerebral vasospasm in SAH patients. RESULTS: 316 patients were analyzed (mean age = 52.97±12.27 years, 52.2% males). There were statistically significant difference rates of the cerebral vasospasm by Hunt and Hess Classification and Fisher classification (p <0.01). The proportion of the patients with cerebral vasospasm who were diagnosed exactly by TCD was 95.2%, while the proportion of the patients without cerebral vasospasm diagnosed exactly was 91.5%. TCD predictive diagnostic value was the highest, with the sensitivity of 0.95 (95% CI: 0.91-0.98), specificity of 0.91 (95% CI: 0.85-0.96), positive predictive value of 0.94 (5% CI: 0.90-0.97) and negative predictive value of 0.93 (95 CI: 0.87-0.97). Hemiplegia was the clinical symptom with the highest diagnostic value with the sensitivity of 0.34 (95% CI: 0.27-0.41), specificity of 0.92 (95% CI: 0.86-0.96), positive predictive value of 0.86 (95% CI: 0.76-0.93) and negative predictive value of 0.49 (95% CI: 0.41-0.54). CONCLUSIONS: Evidence of vasospasm diagnosis on TCD ultrasonography was found with high accuracy. Current study enables to suggest the wide application of TCD in Vietnam health facilities from central to grassroots levels instead of the CTA use.

Effects of a Novel Erectogenic Condom on Men and Women's Sexual Pleasure: Randomized Controlled Trial.

We tested whether CSD500 (Futura Medical; Guildford, UK), a novel condom containing erectogenic gel designed to increase penile firmness, penile size, and erection duration, results in greater sexual pleasure. In 2017-2020, we randomized heterosexual couples in Thanh Hoa, Vietnam to use CSD500 (N = 248) or standard condoms (N = 252) and followed them up for six months. Women completed the Quality of Sexual Experience (QSE) scale; men completed the QSE, Sexual Experience Questionnaire (SEX-Q), and 11 condom acceptability items. Female participants' mean age was 32.1 years (SD = 0.24; range 21-46). QSE scores were higher among women (B, 0.12; 95% CI, 0.03-0.21) and men (B, 0.21; 95% CI, 0.08-0.35) in the CSD500 relative to the control arm. SEX-Q scores were higher among men in the CSD500 compared to the control arm (B, 3.22; 95% CI, 1.53-4.91). Higher proportions of men in the CSD500 relative to the control arm reported the condom felt "natural" during sex (68.6% vs. 32.3%; p < .01) and that sex with the condom felt "a lot better" than condomless sex (15.5% vs. 5.3%; p < .01). Compared with standard condoms, CSD500 use was associated with higher reports of sexual pleasure and condom acceptability.

Auto-detection of cervical collagen and elastin in Mueller matrix polarimetry microscopic images using K-NN and semantic segmentation classification.

We propose an approach for discriminating fibrillar collagen fibers from elastic fibers in the mouse cervix in Mueller matrix microscopy using convolutional neural networks (CNN) and K-nearest neighbor (K-NN) for classification. Second harmonic generation (SHG), two-photon excitation fluorescence (TPEF), and Mueller matrix polarimetry images of the mice cervix were collected with a self-validating Mueller matrix micro-mesoscope (SAMMM) system. The components and decompositions of each Mueller matrix were arranged as individual channels of information, forming one 3-D voxel per cervical slice. The classification algorithms analyzed each voxel and determined the amount of collagen and elastin, pixel by pixel, on each slice. SHG and TPEF were used as ground truths. To assess the accuracy of the results, mean-square error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM) were used. Although the training and testing is limited to 11 and 5 cervical slices, respectively, MSE accuracy was above 85%, SNR was greater than 40 dB, and SSIM was larger than 90%.

[Preconditioning of vascularized high-risk eyes using fine-needle diathermy and cross-linking]. / Präkonditionierung von vaskularisierten Hochrisikoaugen mittels Feinnadeldiathermie und Crosslinking.

BACKGROUND: The risk of allograft rejection following high-risk keratoplasty increases with the area of corneal neovascularization. Pharmaceutical and physical regression of corneal neovascularization before keratoplasty may offer the potential to reduce the risk of graft rejection after high-risk keratoplasty. OBJECTIVE: This article provides a review of the literature on the preconditioning of vascularized high-risk eyes using fine-needle diathermy and corneal cross-linking (preoperative preconditioning by lymphangioregression). METHODS: A literature search was carried out in PubMed and a summary of own data is presented. RESULTS: Animal experimental studies showed that both fine-needle diathermy and corneal cross-linking lead to a regression of corneal neovascularization and prolong graft survival after high-risk keratoplasty. Furthermore, studies from our institute provide first evidence that both procedures also lead to a reduction of corneal neovascularization in the clinical practice and thus potentially reduce the risk of allograft rejection after subsequent high-risk keratoplasty. DISCUSSION: Fine-needle diathermy and corneal cross-linking provide effective therapeutic approaches for angioregressive treatment and seem to prolong graft survival following high-risk keratoplasty. Larger prospective and controlled clinical trials are needed to further investigate these promising therapeutic approaches.

Monte Carlo analysis of optical heart rate sensors in commercial wearables: the effect of skin tone and obesity on the photoplethysmography (PPG) signal.

Commercially available wearable devices have been used for fitness and health management and their demand has increased over the last ten years. These "general wellness" and heart-rate monitoring devices have been cleared by the Food and Drug Administration for over-the-counter use, yet anecdotal and more systematic reports seem to indicate that their error is higher when used by individuals with elevated skin tone and high body mass index (BMI). In this work, we used Monte Carlo modeling of a photoplethysmography (PPG) signal to study the theoretical limits of three different wearable devices (Apple Watch series 5, Fitbit Versa 2 and Polar M600) when used by individuals with a BMI range of 20 to 45 and a Fitzpatrick skin scale 1 to 6. Our work shows that increased BMI and skin tone can induce a relative loss of signal of up to 61.2% in Fitbit versa 2, 32% in Apple S5 and 32.9% in Polar M600 when considering the closest source-detector pair configuration in these devices.

Growth and Oleanolic Acid Accumulation of Polyscias fruticosa Cell Suspension Cultures.

BACKGROUND: Oleanolic acid is an oleanane triterpene found in many plant species all over the world. This compound is also a major saponin in leaves of Polyscias fruticosa and possesses several promising pharmacological activities, such as hepatoprotective effects, and antiinflammatory, antioxidant, or anticancer activities. OBJECTIVE: The objective of the present work is to establish cell suspension culture of P. fruticosa, investigate the influence of several factors such as plant growth regulators and carbon source on cell growth, and determine their oleanolic acid content. METHODS: Cell culture was established by using 2 g fresh weight of 30 day old friable callus derived from in vitro stem segment in 50 mL of liquid medium with a shaking speed of 220 rpm. The culture was then incubated at 25±2ºC with a shaking speed of 120 rpm in the period of 12 h daylight at a light intensity of about 6.75 µmol/m2/s. Cell growth was measured by fresh and dry biomass at 16 h day. Oleanolic acid content was determined using HPLC analysis. RESULTS & DISCUSSION: The study results showed that MS medium containing 2% sucrose as a carbon source, supplemented with 1 mg/L 6-benzylaminopurine and 0.5 mg/L 2,4-dichlorophenoxyacetic acid was the most appropriate growth medium. Cell biomass and oleanolic acid content reached the highest values of 0.43 g dry weight/flask and 25.4 mg/g dry weight, respectively. CONCLUSION: These results indicated the potential production of oleanolic acid, a compound with high pharmacological value, from P. fruticosa cell culture.

Depth-resolved Mueller matrix polarimetry microscopy of the rat cornea.

Mueller matrix polarimetry (MMP) is a promising linear imaging modality that can enable visualization and measurement of the polarization properties of the cornea. Although the distribution of corneal birefringence has been reported, depth resolved MMP imaging of the cornea has not been archived and remains challenging. In this work, we perform depth-resolved imaging of the cornea using an improved system that combines Mueller matrix reflectance and transmission microscopy together with nonlinear microscopy utilizing second harmonic generation (SHG) and two photon excitation fluorescence (TPEF). We show that TPEF can reveal corneal epithelial cellular network while SHG can highlight the presence of corneal stromal lamellae. We then demonstrate that, in confocal reflectance measurement, as depth increases from 0 to 80 µm both corneal depolarization and retardation increase. Furthermore, it is shown that the spatial distribution of corneal depolarization and retardation displays similar complexity in both reflectance (confocal and non-confocal) and transmission measurement, likely due to the strong degree of heterogeneity in the stromal lamellae.

Standing balance of vehicle passengers: The effect of vehicle motion, task performance on post-drive balance.

BACKGROUND: Motion platforms and driving simulators have been shown to contribute to motion sickness and a short-term increase in standing postural sway. However, no studies to date have investigated how the motion of a passenger vehicle and the performance of a task during a drive on a closed test track affects post-drive standing balance. RESEARCH QUESTIONS: What are the effects of (1) a continuous, scripted drive on a closed test track, and (2) the performance of a handheld tablet-based task during the scripted drive, on post-drive standing balance? METHODS: Fifty adults (23 males, 27 females; 40.0 ± 20.6 yr) rode in the front passenger seat of a midsized sedan on a scripted drive. Participants were assigned to one of the acceleration levels (Low, Moderate) and completed both Task and No-Task test conditions, involving a visual-based task on a handheld tablet device. Before and after each scripted drive, participants completed two standing balance exercises: 1) feet tandem, eyes open, on firm support, and 2) feet together, eyes closed, on foam support. An inertial measurement unit (IMU) captured estimates of postural trunk sway. Root-mean-square (RMS) of angular position and velocity in the anteroposterior (A/P) and mediolateral (M/L) directions, and elliptical fit and path length of sway trajectory were computed. A nonparametric analysis was performed on the balance metrics. RESULTS: Exposure to a scripted drive in a vehicle affected participants' postural sway, especially after using a handheld device during the drive. M/L RMS sway velocity and path length increased for both exercises following the scripted drive with task. Additionally, M/L RMS sway increased for the more challenging balance exercise, during which participants stood with feet together on foam support with eyes closed. SIGNIFICANCE: This study is the first to explore balance following a scripted drive on a closed test track. Changes in post-drive balance introduces potential risks to vehicle passengers; concurrent performance of a task on a handheld device further increases the likelihood that post-drive balance will be negatively affected.

Presence of Clostridioides difficile and multidrug-resistant healthcare-associated pathogens in stool specimens from hospitalized patients in the USA.

BACKGROUND: Healthcare-associated infections (HCAIs) continue to be a major cause of morbidity and mortality. Many HCAI pathogens, including multidrug-resistant organisms (MDROs), colonize the gastrointestinal tract. AIM: To determine the frequency of MDRO carriage in patients who do and do not harbour toxigenic Clostridioides difficile in their stools. METHODS: Stool specimens received from nine US laboratories were cultured using media selective for C. difficile, Staphylococcus aureus, vancomycin-resistant enterococci (VRE), and carbapenem-resistant Gram-negative organisms (CROs). Specimens and isolates were also tested by polymerase chain reaction (PCR). Bacterial isolates underwent susceptibility testing and genotyping. FINDINGS: Among 363 specimens, 175 yielded toxigenic C. difficile isolates spanning 27 PCR ribotypes. C. difficile (TCD+) stools harboured an additional 28 organisms, including six CROs (3.4%), of which two (1.1%) were carbapenemase-producing organisms (CPOs), 19 VRE (10.9%), and three meticillin-resistant S. aureus isolates (MRSA, 1.7 %). Stools that were culture negative for toxigenic C. difficile (TCD-) yielded 26 organisms, including four CROs (2.1%), 20 VRE (10.6), and two MRSA (1.1%). Excluding C. difficile, no significant differences were seen in the rates of the MDROs between TCD+ and TCD- specimens. CONCLUSION: Overall, 15.4% of the TCD+ stools and 11.2% of the TCD- stools carried at least one non-C. difficile MDRO pathogen, indicating that multiple MDROs may be present in the gastrointestinal tracts of patients, including those that harbour C. difficile.

Invasive rhino-orbital-cerebral aspergillosis in an immunocompetent patient.

INTRODUCTION: Rhino-orbital-aspergillosis (ROA) is a rare but serious disease in immunocompetent patients. Diagnosis is often delayed due to the absence of specific clinical symptoms. We describe the case of a patient who presented initially with ROA which spread progressively to the right ethmoid-sphenoid sinuses and then to the brain. OBSERVATION: A 61-year-old patient with a history of well-controlled diabetes presented with a sudden severe decrease in right visual acuity. Cerebral MRI showed the presence of an infiltrate in the right orbital apex extending to the homolateral cavernous sinus without any cerebral involvement. A diagnosis of right orbital myositis was made and corticosteroid therapy was started. His symptoms worsened progressively leading to quasi-blindness. A new MRI showed the development of right sphenoid-ethmoid osteolytic lesions. A fungal aetiology was suspected and tests for fungal biomarkers found a ß-(1-3)-D-glucan level of 99pg/ml but negative galactomannan. An ethmoid biopsy was performed for histological and mycological investigations, including the detection of Aspergillus DNA by qPCR. qPCR was positive and culture resulted in the isolation of multi-sensitive Aspergillus fumigatus. Treatment was initiated with voriconazole. Due to persistence of blindness and the appearance of a lesion extending to the right frontal lobe, surgical excision was performed followed by antifungal treatment for a total duration of 1year. The patient is currently stable, but has persistence of blindness in the right eye. CONCLUSION: Invasive ROA is a rare but serious disease in immunocompetent patients which should be evoked in the differential diagnosis of a tumour or vasculitis. Early diagnosis is essential for optimal management.

Beyond diffuse correlations: deciphering random flow in time-of-flight resolved light dynamics.

Diffusing wave spectroscopy (DWS) and diffuse correlation spectroscopy (DCS) can assess blood flow index (BFI) of biological tissue with multiply scattered light. Though the main biological function of red blood cells (RBCs) is advection, in DWS/DCS, RBCs are assumed to undergo Brownian motion. To explain this discrepancy, we critically examine the cumulant approximation, a major assumption in DWS/DCS. We present a precise criterion for validity of the cumulant approximation, and in realistic tissue models, identify conditions that invalidate it. We show that, in physiologically relevant scenarios, the first cumulant term for random flow and second cumulant term for Brownian motion alone can cancel each other. In such circumstances, assuming pure Brownian motion of RBCs and the first cumulant approximation, a routine practice in DWS/DCS of BFI, can yield good agreement with data, but only because errors due to two incorrect assumptions cancel out. We conclude that correctly assessing random flow from scattered light dynamics requires going beyond the cumulant approximation and propose a more accurate model to do so.

Time-of-flight resolved light field fluctuations reveal deep human tissue physiology.

Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.

Warmblood fragile foal syndrome type 1 mutation (PLOD1 c.2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed.

BACKGROUND: Catastrophic fractures are among the most common cause of fatalities in racehorses. Several factors, including genetics, likely contribute to increased risk for fatal injuries. A variant in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase1 gene (PLOD1 c.2032G>A) was shown to cause Warmblood fragile foal syndrome type 1 (WFFS), a fatal recessive defect of the connective tissue. Screening of multiple horse breeds identified the presence of the WFFS allele in the Thoroughbred. PLOD1 is involved in cross-linking of collagen fibrils and thus could potentially increase the risk of catastrophic breakdown. OBJECTIVES: Estimate the frequency of the WFFS allele (PLOD1 c.2032G>A) and determine if it is a risk factor for catastrophic breakdown in the Thoroughbred. STUDY DESIGN: Case-control genetic study. METHODS: Genomic DNA from hair and/or tissue samples was genotyped for the WFFS allele. Fisher's Exact tests were performed to compare allele and carrier frequencies between the case cohort (catastrophic breakdown, n = 22) and several cohorts with no record of injury (n = 138 raced/trained at same track and season and n = 185 older than 7 years and raced during same season), nonracers (n = 92), and a random sample without consideration for racing history (n = 279). RESULTS: The frequency of the PLOD1 c.2032G>A variant in the Thoroughbred breed is low (1.2%). Seventeen of 716 Thoroughbreds tested were carriers (2.4%) and no WFFS homozygotes were detected. Only one catastrophic breakdown case carried the WFFS allele. No statistically significant difference in allele or carrier frequency was identified between case and control cohorts (P>0.05 in all comparisons performed). MAIN LIMITATIONS: This study evaluated cases from one single track. CONCLUSIONS: This study demonstrated that the PLOD1 c.2032G>A associated with WFFS is present at very low frequency in Thoroughbreds and is not a genetic risk factor for catastrophic breakdown.