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Inferring the number and locations of knots in spline regression remains a difficult problem due to the varying dimensionality of the parameter space and the non-differentiability of the likelihood function. In this paper, we propose a Bayesian framework for knot inference in multivariate spline regression, supported by prior specifications that account for model complexity. By accurately estimating the knot number and locations, this approach addresses several complex tasks, including fitting discontinuous multivariate functions, detecting univariate change points, and identifying peak locations in multivariate regression. We evaluate the proposed method through extensive simulation studies and demonstrate its practical utility by analyzing real-world datasets, including triceps skinfold thickness measurements and functional magnetic resonance imaging data from the Human Connectome Project. The results underscore the superior performance of our approach compared to existing methods.

Alcohol-induced blackouts (AIBs) are a common and serious consequence of drinking in young adults. AIBs are associated with experiencing increased alcohol-related consequences. To inform efforts to reduce alcohol-related harms on especially risky drinking days that result in AIBs, we sought to identify contextual factors that contribute to excess AIB-associated harms. This study aims to (1) examine relationships between AIBs and four consequence domains; and (2) explore how these relationships differ by social context and location. Young adults (N = 175, 52.6% female, 86.9% White, Mage = 20.8) with recent heavy drinking and AIBs wore alcohol sensors and completed surveys about their consequences (including AIBs) and the social context and locations in which drinking occurred over six weekends. Four consequence domains included positive (reflective of desired alcohol expectancies), common (relatively acute, low potential for personal harm), uncommon (relatively serious, i.e., sexual, legal, great potential for personal harm), and alcohol-related problems (related to impaired control and physical dependence). Multilevel structural equation models were conducted to test for main effects of AIBs and moderating effects of contextual factors. AIBs were significantly associated with experiencing 15% more positive consequences, 205% more common consequences, 367% more uncommon consequences, and 166% more alcohol-related problems. AIBs were more strongly associated with common consequences and alcohol-related problems when drinking occurred exclusively with family, friend(s), and/or a romantic partner (vs. with a large group). AIBs were also more strongly associated with common consequences when drinking took place exclusively at a residential location (vs. non-residential). No other significant moderating effects were observed. Days with an AIB were associated with experiencing significantly more positive and negative alcohol-related consequences compared to days without an AIB. Our findings support the notion that the context in which drinking occurs is an important consideration for reducing alcohol-related harms.

Bioaerosols are critical components of the atmospheric environment, yet their accurate characterization remains challenging due to the lack of a standardized sampling methodology. In this study, we compared three commonly used bioaerosol samplers- a swirling collector, a condensational growth tube collector, and a cascade impactor-to evaluate their performance in capturing bacterial diversity, community composition, and number concentrations at two distinct locations on a university campus. The bacterial communities were analyzed using 16S rRNA gene amplicon sequencing. The results revealed significant differences in the bioaerosol number concentrations and the composition of bacterial communities across the samplers. Among the three samplers, the condensational growth tube collector recorded the highest overall concentration, with a lower alpha diversity than the other sampler types. Analysis of the 678 identified unique genera indicated that only 24% were collected by all three samplers, underscoring that no single device can comprehensively represent airborne bacterial diversity. However, all three samplers consistently identified distinct locational differences in key bacterial taxa, notably the increased abundance of agriculture-associated genera near the livestock-rearing facility. This indicates that each sampler was able to capture and reveal dominant genera under different environments. PERM-ANOVA results showed that the type of bioaerosol sampler was responsible for more variance in bacterial community composition than sampling location, highlighting the dominant role of sampler selection in shaping observed microbial profiles. Overall, the variability in performance of samplers may be influenced by factors such as particle size distribution, bacterial community composition, sampling mechanism, and sampling medium. These findings underscore the critical importance of selecting appropriate bioaerosol sampling instruments based on targeted microbial communities and specific environmental conditions; the findings also provide a framework for refining sampling methodologies to enhance the accuracy and comparability of bioaerosol studies.

Out-of-Hospital Emergency Medical Services (OHEMS) play a critical role in providing timely care for patients experiencing acute medical emergencies. Traditionally focused on rapid response and transport, OHEMS are increasingly evolving toward a more comprehensive role within the healthcare system. This scoping review aims to map existing modeling approaches, identify research streams and to examine whether recent developments in practice can also be found in the modeling literature. Following the PRISMA extension for Scoping Reviews, a structured search was conducted in PubMed, Google Scholar, Semantic Scholar, and IEEE. We included English-language case studies and review articles published between 2010 and 2024 that addressed modeling, optimization, forecasting, or decision-support approaches in out-of-hospital emergency medical services. Studies were classified using the Emergency Care Pathway framework, with additional extraction of methodological approach, data source, geographical context, performance indicators and implementation perspective. We included 150 methodological case studies and 33 review papers. Location and relocation problems were the most frequently addressed topics, and response time served as the primary model performance evaluation indicator. The analyzed literature showed increasing methodological diversification, including simulation-optimization, online and real-time optimization, decision support systems, machine learning-based forecasting, and GIS-supported spatial analysis. In contrast, workload-aware models and equity-oriented approaches have also emerged, although they remain less prominent. A limited but growing number of scholars provide model code to support reproducibility and practical uptake. Yet, cooperation between modelers and practice remains limited. Regarding changes in the provision of OHEMS care, results of this study indicate that these have not yet been reflected by modelers. Evidence by this study indicates that OHEMS modeling has evolved from predominantly static location and coverage models toward more dynamic, data-driven, real time decision support and to some extent implementation-oriented approaches. However, many models still conceptualize OHEMS primarily as a rapid response and transport system. Derived from the review findings, we propose the incorporation of a more dimensional framework into modeling approaches that considers finance and public health structure as well as expected quality. Further, based on the notion of Right Time, Right Care, and Right Place, implementing clinically meaningful time metrics, alternative response options, workload and staff constraints, and care pathways beyond transport to hospital may prove useful.

Greater trochanteric (GT) fractures after total hip arthroplasty (THA) are typically managed nonoperatively. However, outcome data for patient counseling remain limited. We evaluated the nonoperative results, focusing on fracture union rates and the presence of persistent limp in relation with fracture location, displacement magnitude, and direction. We retrospectively reviewed 82 postoperative GT fractures not associated with trochanteric osteolysis following primary THA performed between 1984 and 2020. The mean follow-up was 9 years. Fracture location was classified relative to the contralateral lesser trochanter as tip, waist, or base. Initial displacement, migration, final displacement, and bony union were assessed radiographically. Clinical outcomes included the presence of a persistent limp and Harris Hip Score. Multivariable analyses were performed to identify factors associated with nonunion and limp. Fractures were classified as tip (n = 32), waist (n = 29), or base (n = 21). The mean initial displacement was 8.9 mm, with 43% displaced >10 mm. Initial displacement was significantly lower in base fractures (4.8 mm) compared with tip (10.1 mm) or waist (10.8 mm) fractures (p < 0.05). The mean final displacement was 14.6 mm. 45% of fractures achieved complete bony union, and 38% of patients demonstrated a persistent limp. In multivariable analysis, greater final displacement (>12 mm), and tip and waist fractures were independently associated with nonunion. Posterior fracture displacement was significantly associated with persistent limp. Outcomes following nonoperative management of GT fractures after THA depend on fracture morphology and displacement characteristics. Tip and waist fractures and fractures with final displacement >12 mm have a higher risk of nonunion, whereas posterior and superior displacement is associated with persistent limp. Greater than 20 mm of displacement is associated with both limp and nonunion. These findings may assist surgeons in counseling patients and in identifying fracture patterns at higher risk for adverse outcomes of nonoperative management. Level III (Prognostic Study). See Instructions for Authors for a complete description of levels of evidence.

Sentinel lymph node mapping (SLNM) has emerged as a key technique to guide decisions regarding nodal extirpation in dogs with oromaxillofacial tumours. The primary aims of this retrospective study were to describe the clinical utility of indirect computed tomographic lymphangiography (ICTL) for SLNM in a large cohort of dogs, characterise variability in SLN drainage patterns by tumour location, and describe the distribution of metastatic lymph nodes (LNs) identified by SLNM guided cytology or pathology. SLN locations, cytology, and available histopathology were reported as descriptive data. ICTL data were evaluated for 77 oromaxillofacial tumours in 74 dogs. A median of 2 SLNs were identified per ICTL dataset with 92% having at least one SLN identified. The ipsilateral mandibular lymphocentrum was the most common drainage basin; however, contralateral or bilateral drainage was frequent, occurring in over 55% of rostral tumours. Lateralized tumours were associated with a higher frequency of ipsilateral mandibular SLN identification compared with non-lateralized tumours (p&#x2009;=&#x2009;0.0009). Of 68 dogs with malignant tumours, 10 (15%) had LN metastasis. Metastasis occurred in the SLN (n&#x2009;=&#x2009;8), outside the SLN (n&#x2009;=&#x2009;1), and in one dog without any identifiable SLNs. In 4 dogs (40%), metastasis extended beyond the ipsilateral lateral MLN; 3 dogs had metastasis exclusively in the medial retropharyngeal LNs. Among dogs with paired cytology and pathology, the false-negative rate of SLN cytology was 6.9%, potentially offering a low-morbidity screening method prior to LN extirpation. Future studies should seek to evaluate how SLNM with guided LN sampling influences patient outcomes, given its clinical feasibility.

Comparing angiographic findings of patients presenting with acute coronary syndrome (ACS) in the Middle East/Gulf (MEG) and North America (NA) may shed light onto how coronary artery disease (CAD) complexity at time of ACS presentation impacts immediate management and clinical outcomes. Therefore, we compared outcomes in concurrent ACS patients between MEG and NA. Consecutive patients with ACS were identified at 2 locations in an international health system. Extent of epicardial coronary disease was determined using Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score by trained investigators at both locations and compared using appropriate testing. In addition, in-hospital outcomes, including death, stroke and major bleeding were compared between the two groups. Between January and December 2017, 158 patients in MEG and 381 in NA were admitted with ACS. Patients in MEG were younger (57.3&#xb1;11.5 vs. 65.0&#xb1;12.1 years; P<0.001) than those in NA, more likely to have diabetes (51.9% vs. 28.9%; P<0.001). MEG patients had more complex CAD (SYNTAX score: 23.5&#xb1;12.3 vs. 13.2&#xb1;8.6; P<0.001) and were more likely to receive surgical or hybrid revascularization [odds ratio (OR) 2.1, 95% confidence interval (CI): 1.4-3.1] but less likely to receive percutaneous coronary interventions (OR 0.3, 95% CI: 0.2-0.5). These findings suggest that patients in the MEG present at the time of their first clinical event with more severe CAD, potentially driven by a higher prevalence and poorer control of diabetes. Further studies are needed to explore genetic, environmental, and metabolic factors contributing to rapid CAD progression in MEG populations.

To characterize changes in the retinal pigment epithelium (RPE) in pediatric combined hamartoma of the retina and RPE (CHRRPE) using wide-field swept-source optical coherence tomography (SS-OCT) and to identify factors associated with RPE involvement. We conducted a retrospective study of children with CHRRPE diagnosed between 2018 and 2023 at Zhongshan Ophthalmic Center and imaged with wide-field SS-OCT. RPE alterations were defined using OCT features and classified as RPE deformation without discontinuity or RPE disruption with secondary changes. Factors associated with RPE involvement were evaluated using multivariable logistic regression analyses. Forty-one eyes from 38 children (21 boys; median age, 7 years) were included. OCT showed preretinal fibrosis in 21 of 41 eyes (51%), mini-folds in 38 of 41 eyes (93%), and maxi-folds in 32 of 41 (78%). RPE involvement was detected in 11 of 41 eyes (27%), including RPE-originated vertical striae (8/41 [20%]), outer retinal hyper-reflective pigment clumps (7/41 [17%]), RPE protrusion (6/41 [15%]), RPE rupture (5/41 [12%]), and choroidal neovascularization (5/41 [12%]). RPE alterations occurred in all peripheral lesions (3/3), 50% of peripapillary lesions (3/6), and 16% of macular lesions (5/32). Multivariable analysis indicated extramacular location (odds ratio, 11.29; 95% confidence interval, 1.45-87.81; P = 0.021) and preretinal fibrosis (odds ratio, 7.08; 95% confidence interval, 1.14-44.00; P = 0.036) were associated with RPE involvement. In pediatric CHRRPE, RPE involvement was not uncommon and was associated with extramacular location and preretinal fibrosis. Wide-field SS-OCT may help to identify structural features in pediatric CHRRPE. Characterizing swept-source optical coherence tomography patterns in children with combined hamartoma of the retina and retinal pigment epithelium links retinal pigment epithelium damage to inner retinal contraction and supports risk stratification and follow-up planning.

Deep brain stimulation (DBS) treats various movement disorders, though routine battery replacement is required. Factors affecting battery life remain unclear; prior studies implicate programming parameters and device model. Advancements in intraoperative guidance enable DBS placement under general anaesthesia (GA) using direct targeting instead of conscious sedation (Monitored anesthesia care or MAC) using indirect targeting. This study examines the effect of DBS anaesthesia type on IPG battery longevity and other influencing factors. Retrospective chart review of 254 patients who underwent DBS placement between 2013 and 2023 at a tertiary care centre was completed under an IRB-approved protocol, 217 of whom met inclusion criteria. Using an accelerated failure time (AFT) model, battery longevity was assessed as a function of anaesthesia type, electrode location, stimulation parameters, diagnosis, demographics, Movement Disorder Society Unified Parkinson's Disease Rating Scale part III score (MDS-UPDRS-III) and battery type. DBS implanted with MAC resulted in significantly reduced battery longevity, AFT coefficient=-0.149, 95%&#x2009;CI -0.27 to -0.03 (p<0.05) compared with GA. compared with globus pallidus interna, subthalamic nucleus implantation (AFT coefficient=0.223, 95%&#x2009;CI 0.10 to 0.35, p<0.05) and thalamic ventral intermediate nucleus (VIM) implantation (AFT coefficient=0.134, 95%&#x2009;CI 0.01 to 0.26, p<0.05) were associated with significantly longer battery longevity. High amplitude settings significantly reduced battery longevity, AFT coefficient=-0.167, 95%&#x2009;CI -0.21 to -0.12 (p<0.05). Diagnosis, MDS-UPDRS-III score and battery model effects on IPG battery longevity were not statistically significant. Battery longevity can be optimised by considering anaesthesia type and electrode location during implantation. Improved battery longevity reduces replacement frequency, associated complications and overall healthcare costs.

Germline pathogenic or likely pathogenic variants (GPVs) in BRCA-1 Associated Protein 1 ( BAP1 ) are associated with a spectrum of tumors, including uveal melanoma (UM). Currently, UM patients with BAP1 GPVs are treated as high-risk class 2 tumors based on mostly empiric data. In the current study, we examined the clinical phenotype of a cohort of 29 UM patients with BAP1 GPVs. We also carried out a systematic review of the literature of UM patients with BAP1 GPVs. We observed that UM patients with BAP1 GPVs have significantly lower median age of diagnosis compared to median age reported in UM patients in the Surveillance, Epidemiology, and End Results Program (SEERS) database. Metastatic risk and overall survival in the UM BAP1 GPVs cohort were statistically significant from those in patients with class 1 tumors, but were comparable to those observed in UM patients with class 2 tumors. In UM BAP1 GPVs treated with radiation (n=12), no secondary cancers were observed in the field of radiation in a median 26.5 months (range, 4-119 months) follow up period. One patient experienced a separate growth of UM at a distinct location within the same eye. These data support managing UM in patients with BAP1 GPVs as aggressive class 2 tumors, following the currently established standard of care for these high-risk tumors. A small percent of uveal melanomas is attributed to inherited (germline) pathogenic variants in the BAP1 gene. The clinical outcome of these patients is unclear. We studied clinical characteristics, secondary tumors and survival outcomes of uveal melanoma patients with germline BAP1 pathogenic variants. Uveal melanoma patients with germline BAP1 pathogenic variants were more likely to be diagnosed earlier and their survival outcomes were poorer than those with class 1 tumors, but similar to those with class 2 tumors. In patients treated with radiation, no secondary malignancies were observed but one UM patient had a separate growth of UM at distinct location within the same eye.

High-impact sports participation may exacerbate pelvic floor dysfunctions (PFDs), a condition already common among women, in the female athletic population. In this population, pelvic floor health knowledge (PFHK) is key to preventing dysfunctions and sustaining performance. It was hypothesized that PFHK and dysfunctions in female athletes would differ according to age, education level, marital status, sport type, years of sports participation, and physical activity level. A total of 127 female athletes aged 16-40&#xa0;years were recruited from various sports disciplines. Pelvic floor health knowledge (Pelvic Floor Health Knowledge Quiz), pelvic floor dysfunctions (Pelvic Floor Distress Inventory-20, PFDI-20), and physical activity levels (International Physical Activity Questionnaire-Short Form) were measured. The Mann-Whitney U test and Spearman correlation were used for statistical analysis. The mean age of participants was 21.1&#x2009;&#xb1;&#x2009;5.3&#xa0;years, with 10.2&#x2009;&#xb1;&#x2009;5.3&#xa0;years of sports participation. While 91.3% correctly identified the pelvic floor location, awareness of pelvic floor muscle training was limited. Athletes&#x2009;>&#x2009;20&#xa0;years and those with bachelor's or postgraduate education had significantly higher pelvic floor health knowledge (p&#x2009;<&#x2009;0.05). Sports participation (>&#x2009;10&#xa0;years) was associated with higher risk/etiology and total scores (p&#x2009;<&#x2009;0.05). PFDI-20 scores showed no significant correlations with demographic or sport-related variables (p&#x2009;>&#x2009;0.05). While female athletes identify the pelvic floor's location, their knowledge of its function and treatment remains limited; therefore, integrating targeted education into athletic programs is essential to mitigate dysfunction risks and optimize long-term performance.

Neurofibromatosis type 1 (NF1) is a genetic disorder occasionally complicated by vasculopathy, but the concurrence of NF1, a ruptured distal anterior cerebral artery (ACA) aneurysm, and moyamoya syndrome is exceedingly rare. Literature review revealed that fewer than 20 such cases have been reported in English publications to date. The management of such complex, multifocal cerebrovascular pathology-including the choice of therapy, the risk of procedural complications, and the need for lifelong surveillance-poses significant challenges. A 44-year-old man with clinical features of NF1 presented with sudden headache, dizziness, and transient syncope. Imaging revealed a ruptured saccular aneurysm arising from the right A3 segment of the ACA, accompanied by intraventricular hemorrhage and contralateral moyamoya-like vasculopathy. Given the aneurysm's deep pericalosal location, small size, and the patient's multiple scalp neurofibromas, endovascular coil embolization was selected over microsurgical clipping. The procedure was successfully performed via a transfemoral approach, achieving complete aneurysm occlusion with preservation of the parent artery. The patient recovered well neurologically. Remarkably, digital subtraction angiography at more than five years post-embolization confirmed durable occlusion of the treated aneurysm without recurrence. However, it also demonstrated progression of the moyamoya syndrome and revealed a new, untreated aneurysm at the right ophthalmic segment. This case illustrates that endovascular coil embolization can be a safe and effective first-line treatment for ruptured distal ACA aneurysms in the complex setting of NF1 vasculopathy, providing long-term protection from rebleeding. The long-term follow-up uniquely highlights that NF1-associated cerebrovascular disease is progressive and multifocal; successful treatment of an index ruptured aneurysm does not eliminate the risk of new lesions elsewhere. Therefore, indefinite vascular surveillance is warranted in these patients. This report underscores the importance of a tailored, multidisciplinary approach and lifelong monitoring in managing NF1-related cerebrovascular complications.

Even though lipomas are the most common benign soft tissue tumors, their occurrence in the hand is relatively uncommon. Giant lipomas, defined as those larger than 5 cm, are exceedingly rare in this location. In the hand, lipomas may occur in subcutaneous tissue, within intramuscular or intermuscular spaces, and may occasionally present with functional impairment or digital paresthesia due to compression of adjacent neurovascular structures. While most lesions are benign, large or atypical masses require careful evaluation to exclude malignancy. Magnetic resonance imaging is the preferred imaging modality for preoperative assessment, while histopathological examination confirms the diagnosis. We present the case of a 41-year-old Greek Caucasian woman with a progressively enlarging mass in the left hand over a 3-month period, associated with the recent onset of pain and paresthesia. Imaging findings were consistent with a lipomatous lesion, which was successfully treated with marginal excision. Histopathological analysis confirmed the presence of a benign lipoma. Giant lipomas of the hand are rare and may mimic malignant tumors; therefore, their evaluation requires careful clinical assessment, appropriate imaging, and histopathological confirmation for accurate diagnosis and optimal management.

Colorectal cancer (CRC) incidence and mortality rates differ by population, and evidence suggests that genetic differences may affect cancer biology. However, studies investigating CRC variants in genetically heterogeneous populations are limited. Using somatic tumor mutation profiling of CRCs diagnosed in African Americans (AAs), Ghanaians, Ethiopians, and NHWs, we explore correlations between population group and population-specific tumor variants. Somatic DNA from CRC tumors resected from 150 individuals, including 43 AAs (27%), 53 NHWs (35%), 21 Ghanaians (14.2%), and 33 Ethiopians (22.3%), was sequenced on the Illumina NovaSeq platform, targeting 290 genes. We compared mutations in AAs, Ghanaians, and Ethiopians to those in NHWs to identify variants enriched in historically underrepresented groups. US cohort tumors were diagnosed at significantly younger ages with more early-onset cases (<50 years old) than African cohorts ( p <0.05). Significant differences were observed in primary tumor location, MMR phenotypes, KRAS mutations, and distribution of tumor mutational burden by population. BRAF V600E mutations were rare across all groups, while non- V600E BRAF mutation rates were higher in AA and NHW (43-44%) than Ethiopian and Ghanaian (14-33%) samples. Population-specific differences were identified in mutation rates of APC, CTNNB1, RNF43, PIK3CA, and TP53 , as well as in pathogenic variant occurrence. Geographic origin and age of onset appear to shape the CRC mutational landscape. The similarity between AA and NHW tumor profiles likely reflects their shared predominance of early-onset cases, suggesting that age- and geography-associated factors, including environmental exposures, may influence tumor phenotypes.

Narrative recall is widely used to detect cognitive impairment, but dominant instruments carry proprietary restrictions. The Craft Story 21 (CS), the non-proprietary NACC UDS4 standard, is not available standalone. Here, we validate the freely available Puppy Escape (PE). 346 participants (153 cognitively normal, 106 subjective cognitive impairment, 87 mild cognitive impairment) completed PE and CS. Analyses evaluated convergent and criterion validity, MCI-vs-control discrimination, and incremental validity. PE and CS converged (r=.43-.47) and were equivalent on 10/12 neuropsychological measures. PE Delayed discriminated MCI from controls (d=1.03; ROC-AUC equal to CS, DeLong p=.510) and added variance beyond CS (&#x394;R&#xb2;=+.054, p<.001). Automated subscores revealed MCI deficits in location, action, and name content. PE-18 short form retained discrimination (d=1.02) with 18 items. PE matched CS across all validation domains and captured complementary diagnostic information. PE and PE-18 are available via online registration explicitly permitting industry-sponsored research and fee-for-service clinical use.

Diabetes has emerged as a major health challenge, evident by the rapid rise of cases. As per the National Family Health Survey-5 (NFHS-5), high blood sugar levels have been reported among 13.5% of Indian women and 15.6% of Indian men. However, nearly half of the population with diabetes is estimated to be undetected, especially adults. Diabetes-related comorbidities can be prevented by detecting the high risk at an early stage through assessment and screening of this large pool of adults. The objective of this study was to assess the risk of type 2 diabetes mellitus (T2DM)among the adult population. A community-based cross-sectional survey was carried out at Jodhpur, Rajasthan, including 271 adults selected using a multistage sampling method. Data were collected through an interview schedule consisting of sociodemographic characteristics and assessment of lifestyle and behavioral, physical, and biochemical parameters. The Indian Diabetes Risk Score (IRDS) was used to assess the risk of diabetes. Data were analyzed with the help of SPSS version 25. The adults' mean age was 40.64 &#xb1; 13.21 years, and 26.5% of them mentioned having a family history of T2DM. In this location, most adults have a moderate (40%) to high (31%) risk of developing T2DM. About 25.5% of the adults have other co-morbidities. Age, gender, education, occupation, comorbidity, family history of diabetes, history of tobacco, physical activity, and body mass index were significantly associated with an increased risk for developing diabetes ( P < 0.05). A significant proportion of the adults were found to have a high-to-moderate risk. Poor lifestyle behaviors can further aggravate the situation. This calls for an urgent action plan to promote lifestyle behavior modifications and combat the ever-increasing burden of diabetes among this age group.

Monitoring medical imaging data is increasingly important in healthcare because image-derived quantitative features provide valuable information for assessing disease progression, diagnostic quality, and process stability. However, such data are often feature-rich, distributionally complex, and limited in sample size, and existing methods do not always provide a unified way for retrospectively monitoring joint changes in mean and covariance without relying on strong parametric assumptions. Motivated by these challenges, this paper develops a Phase I nonparametric change-point monitoring framework for individual observations. The framework combines existing high-dimensional two-sample statistics for mean and covariance changes into two control chart schemes, whose control limits are determined through simulation. A post-signal diagnostic procedure is also presented to estimate the change-point location, identify whether the detected shift occurs in the mean, the covariance, or both, and screen potentially affected variables. An extensive simulation study considering various distributional models shows that the proposed charts preserve the nominal in-control false alarm probability, achieve favorable out-of-control detection power, and yield informative post-signal diagnostic results. Finally, a real-world colposcopy dataset is used to illustrate the practical applicability of the proposed framework for the retrospective monitoring of medical imaging data.

Finding suitable therapies for treatment-refractory neuropsychiatric disorders constitutes a major goal for translational neuroscience. Deep brain stimulation shows promise for treatment resistant depression, but treatment efficacy varies substantially across patients. Objective, electrophysiologically driven strategies to optimize deep brain stimulation for treatment resistant depression could greatly improve clinical efficacy by minimizing the trial-and-error approach needed to personalize stimulation settings. This may not only reduce the delay between the start of the treatment and symptom improvement, but also enable acute, real-time verification of circuit engagement, advancing our understanding of the mechanism mediating antidepressant effects. Here, we investigate whether cerebro-cerebral evoked potentials elicited through different deep brain stimulation configurations could be used to guide stimulation personalization for treatment resistant depression. Cerebro-cerebral evoked potentials offer a fast, objective way to identify regions engaged by stimulation, revealing the effective connectivity pattern of the stimulated location. Data were collected from eight patients with treatment resistant depression who received dual bilateral deep brain stimulation devices targeting the subcallosal cingulate and ventral capsule/ventral striatum. During an initial in-hospital monitoring period, single-pulse electrical stimulation was delivered through the deep brain stimulation devices and cerebro-cerebral evoked potentials were recorded through temporary stereo-electroencephalography probes across fronto-temporal regions. Patients underwent several outpatient stimulation programming sessions over the course of 9 months to identify the stimulation configurations leading to the greatest improvement in depressive symptoms. We retrospectively analysed cerebro-cerebral evoked potentials obtained in response to stimulation of different stimulation configurations to identify features distinguishing the clinically effective configurations. The deep brain stimulation configurations leading to the greatest improvement in depressive symptoms were associated with significantly larger evoked potentials in the orbitofrontal cortex and showed an increased number of evoked potentials across dorsal and ventral prefrontal regions. Waveform similarity analysis revealed a gradient in therapeutic effects, such that multiple alternative stimulation configurations led to similar symptom improvement. The vast deep brain stimulation parameter space might contain a configuration subspace defined by comparable therapeutic effects. In addition, evoked potentials obtained from single-pulse and from bursts of high-frequency stimulation displayed similar spatial patterns, suggesting that either method might be able to identify the configuration best engaging the circuit mediating the clinical response. Together, these findings provide proof-of-principle evidence that stimulation-evoked prefrontal responses reflect network engagement associated with antidepressant effects. Cerebro-cerebral evoked potentials may offer an objective and acute strategy to guide contact selection in deep brain stimulation for treatment resistant depression.