A hypothesis for robust polarization vision: an example from the Australian imperial blue butterfly, Jalmenus evagoras.

The Australian lycaenid butterfly Jalmenus evagoras has iridescent wings that are sexually dimorphic, spectrally and in their degree of polarization, suggesting that these properties are likely to be important in mate recognition. We first describe the results of a field experiment showing that free-flying individuals of J. evagoras discriminate between visual stimuli that vary in polarization content in blue wavelengths but not in others. We then present detailed reflectance spectrophotometry measurements of the polarization content of male and female wings, showing that female wings exhibit blue-shifted reflectance, with a lower degree of polarization relative to male wings. Finally, we describe a novel method for measuring alignment of ommatidial arrays: by measuring variation of depolarized eyeshine intensity from patches of ommatidia as a function of eye rotation, we show that (a) individual rhabdoms contain mutually perpendicular microvilli; (b) many rhabdoms in the array have their microvilli misaligned with respect to neighboring rhabdoms by as much as 45 deg; and (c) the misaligned ommatidia are useful for robust polarization detection. By mapping the distribution of the ommatidial misalignments in eye patches of J. evagoras, we show that males and females exhibit differences in the extent to which ommatidia are aligned. Both the number of misaligned ommatidia suitable for robust polarization detection and the number of aligned ommatidia suitable for edge detection vary with respect to both sex and eye patch elevation. Thus, J. evagoras exhibits finely tuned ommatidial arrays suitable for perception of polarized signals, likely to match sex-specific life history differences in the utility of polarized signals.

Multiplexing potential of NIR resonant and non-resonant Raman reporters for bio-imaging applications.

Multiplexed imaging, which allows for the interrogation of multiple molecular features simultaneously, is vital for addressing numerous challenges across biomedicine. Optically unique surface-enhanced Raman scattering (SERS) nanoparticles (NPs) have the potential to serve as a vehicle to achieve highly multiplexed imaging in a single acquisition, which is non-destructive, quantitative, and simple to execute. When using laser excitation at 785 nm, which allows for a lower background from biological tissues, near infrared (NIR) dyes can be used as Raman reporters to provide high Raman signal intensity due to the resonance effect. This class of imaging agents are known as surface-enhanced resonance Raman scattering (SERRS) NPs. Investigators have predominantly utilized two classes of Raman reporters in their nanoparticle constructs for use in biomedical applications: NIR-resonant and non-resonant Raman reporters. Herein, we investigate the multiplexing potential of five non-resonant SERS: BPE, 44DP, PTT, PODT, and BMMBP, and five NIR resonant SERRS NP flavors with heptamethine cyanine dyes: DTTC, IR-770, IR-780, IR-792, and IR-797, which have been extensively used for biomedical imaging applications. Although SERRS NPs display high Raman intensities, due to their resonance properties, we observed that non-resonant SERS NP concentrations can be quantitated by the intensity of their unique emissions with higher accuracy. Spectral unmixing of five-plex mixtures revealed that the studied non-resonant SERS NPs maintain their detection limits more robustly as compared to the NIR resonant SERRS NP flavors when introducing more components into a mixture.

Positive mental health framework of transdiagnostic protective factors in elucidating the association between adverse childhood experiences and severe mental disorders.

OBJECTIVES: Transdiagnostic risk factors-disrupted processes common to psychopathology-link adverse childhood experiences to severe mental disorders (i.e. major depressive disorder, bipolar disorder, and schizophrenia spectrum disorders); however, transdiagnostic protective factors are understudied. The present study investigated the association between a positive mental health framework of protective intra- and interpersonal resources and severe mental disorders in individuals with adverse childhood experiences. We hypothesized that (1) individuals with adverse childhood experiences will experience more severe mental disorders and poorer intra- and interpersonal resources than those without adverse childhood experiences; (2) intrapersonal (e.g. general coping) and interpersonal resources (e.g. emotional support) will interact to predict severe mental disorders. METHODS: A total of 1929 adults participated in this population-based study. Participants were assessed for adverse childhood experiences, severe mental disorders, and intra- and interpersonal resources (general coping, general affect, emotional support, interpersonal skills, spirituality, and personal growth and autonomy) via structured interviews and self-reports. RESULTS: As hypothesized, individuals with adverse childhood experiences (62.6%) experienced more severe mental disorders and poorer intra- and interpersonal resources than those without adverse childhood experiences. Among those with adverse childhood experiences, emotional support interacted with general coping and general affect to predict severe mental disorders; general coping and general affect were negatively associated with severe mental disorders at high (+1 SD) and low (-1 SD) emotional support, respectively. CONCLUSIONS: The present study identified interactions between specific intrapersonal (i.e. general coping and general affect) and interpersonal resources (i.e. emotional support); knowing among whom and when to intervene are essential for optimal treatment of adverse childhood experiences and severe mental disorders.

Impact of device length on electrogram sensing in miniaturized insertable cardiac monitors.

BACKGROUND: Little data exists on electrogram sensing in current generation of miniaturized insertable cardiac monitors (ICMs). OBJECTIVE: To compare the sensing capability of ICM with different vector length: Medtronic Reveal LINQ (~40 mm) vs. Biotronik Biomonitor III (BM-III, ~70 mm). METHODS: De-identified remote monitoring transmissions from n = 40 patients with BM-III were compared with n = 80 gender and body mass index (BMI)-matched patients with Reveal LINQ. Digital measurement of P- and R-wave amplitude from calibrated ICM electrograms was undertaken by 3 investigators independently. Further, we evaluated the impact of BMI and gender on P-wave visibility. RESULTS: Patients in both groups were well matched for gender and BMI (53% male, mean BMI 26.7 kg/m2, both p = NS). Median P- and R-wave amplitude were 97% & 56% larger in the BM-III vs. LINQ [0.065 (IQR 0.039-0.10) vs. 0.033 (IQR 0.022-0.050) mV, p < .0001; & 0.78 (IQR 0.52-1.10) vs. 0.50 (IQR 0.41-0.89) mV, p = .012 respectively). The P/R-wave ratio was 36% greater with the BM-III (p < .001). The 25th percentile of P-wave amplitude for all 120 patients was .026 mV. Logistic regression analysis showed BM-III was more likely than LINQ to have P-wave amplitude ≥.026 mV (OR 7.47, 95%CI 1.965-29.42, p = .003), and increasing BMI was negatively associated with P-wave amplitude ≥.026 mV (OR 0.84, 95%CI 0.75-0.95, p = .004). However, gender was not significantly associated with P-wave amplitude ≥.026 mV (p = .37). CONCLUSION: The longer ICM sensing vector of BM-III yielded larger overall P- and R- wave amplitude than LINQ. Both longer sensing vector and lower BMI were independently associated with greater P-wave visibility.

A physical phantom for amine chemical exchange saturation transfer (CEST) MRI.

OBJECTIVE: To develop a robust amine chemical exchange saturation transfer (CEST) physical phantom, validate the temporal stability, and create a supporting software for automatic image processing and quality assurance. MATERIALS AND METHODS: The phantom was designed as an assembled laser-cut acrylic rack and 18 vials of phantom solutions, prepared with different pHs, glycine concentrations, and gadolinium concentrations. We evaluated glycine concentrations using ultraviolet absorbance for 70 days and measured the pH, relaxation rates, and CEST contrast for 94 days after preparation. We used Spearman's correlation to determine if glycine degraded over time. Linear regression and Bland-Altman analysis were performed between baseline and follow-up measurements of pH and MRI properties. RESULTS: No degradation of glycine was observed (p > 0.05). The pH and MRI measurements stayed stable for 3 months and showed high consistency across time points (R2 = 1.00 for pH, R1, R2, and CEST contrast), which was further validated by the Bland-Altman plots. Examples of automatically generated reports are provided. DISCUSSION: We designed a physical phantom for amine CEST-MRI, which is easy to assemble and transfer, holds 18 different solutions, and has excellent short-term chemical and MRI stability. We believe this robust phantom will facilitate the development of novel sequences and cross-scanners validations.

Militaries and global health: peace, conflict, and disaster response.

Many countries show a growing willingness to use militaries in support of global health efforts. This Series paper summarises the varied roles, responsibilities, and approaches of militaries in global health, drawing on examples and case studies across peacetime, conflict, and disaster response environments. Militaries have many capabilities applicable to global health, ranging from research, surveillance, and medical expertise to rapidly deployable, large-scale assets for logistics, transportation, and security. Despite this large range of capabilities, militaries also have limitations when engaging in global health activities. Militaries focus on strategic, operational, and tactical objectives that support their security and defence missions, which can conflict with humanitarian and global health equity objectives. Guidelines-both within and outside militaries-for military engagement in global health are often lacking, as are structured opportunities for military and civilian organisations to engage one another. We summarise policies that can help close the gap between military and civilian actors to catalyse the contributions of all participants to enhance global health.

Evaluating False Transfer Rates from the Match-between-Runs Algorithm with a Two-Proteome Model.

Stochasticity between independent LC-MS/MS runs is a challenging problem in the field of proteomics, resulting in significant missing values (i.e., abundance measurements) among observed peptides. To address this issue, several approaches have been developed including computational methods such as MaxQuant's match-between-runs (MBR) algorithm. Often dozens of runs are all considered at once by MBR, transferring identifications from any one run to any of the others. To evaluate the error associated with these transfer events, we created a two-sample/two-proteome approach. In this way, samples containing no yeast lysate (n = 20) were assessed for false identification transfers from samples containing yeast (n = 20). While MBR increased the total number of spectral identifications by ∼40%, we also found that 44% of all identified yeast proteins had identifications transferred to at least one sample without yeast. However, of these only 2.7% remained in the final data set after applying the MaxQuant LFQ algorithm. We conclude that false transfers by MBR are plentiful, but few are retained in the final data set.

Improved Method for Determining Absolute Phosphorylation Stoichiometry Using Bayesian Statistics and Isobaric Labeling.

Phosphorylation stoichiometry, or occupancy, is one element of phosphoproteomics that can add useful biological context (Gerber et al. Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 6940-5). We previously developed a method to assess phosphorylation stoichiometry on a proteome-wide scale (Wu et al. Nat. Methods 2011, 8, 677-83). The stoichiometry calculation relies on identifying and measuring the levels of each nonphosphorylated counterpart peptide with and without phosphatase treatment. The method, however, is problematic in that low stoichiometry phosphopeptides can return negative stoichiometry values if measurement error is larger than the percent stoichiometry. Here, we have improved the stoichiometry method through the use of isobaric labeling with 10-plex TMT reagents. In this way, five phosphatase treated and five untreated samples are compared simultaneously so that each stoichiometry is represented by five ratio measurements with no missing values. We applied the method to determine basal stoichiometries of HCT116 cells growing in culture. With this method, we analyzed five biological replicates simultaneously with no need for phosphopeptide enrichment. Additionally, we developed a Bayesian model to estimate phosphorylation stoichiometry as a parameter confined to an interval between 0 and 1 implemented as an R/Stan script. Consequently, both point and interval estimates are consistent with the plausible range of values for stoichiometry. Finally, we report absolute stoichiometry measurements with credible intervals for 6772 phosphopeptides containing at least a single phosphorylation site.

Chinese Beliefs in Luck are Linked to Gambling Problems via Strengthened Cognitive Biases: A Mediation Test.

Problematic patterns of gambling and their harms are known to have culturally specific expressions. For ethnic Chinese people, patterns of superstitious belief in this community appear to be linked to the elevated rates of gambling-related harms; however, little is known about the mediating psychological mechanisms. To address this issue, we surveyed 333 Chinese gamblers residing internationally and used a mediation analysis to explore how gambling-related cognitive biases, gambling frequency and variety of gambling forms ('scope') mediate the association between beliefs in luck and gambling problems. We found that cognitive biases and scope were significant mediators of this link but that the former is a stronger mediator than the latter. The mediating erroneous beliefs were not specific to any particular type of cognitive bias. These results suggest that Chinese beliefs in luck are expressed as gambling cognitive biases that increase the likelihood of gambling problems, and that biases that promote gambling (and its harms) are best understood within their socio-cultural context.

Outcome of acute myeloid leukemia patients with pulmonary nodules of uncertain etiology receiving allogeneic hematopoietic progenitor cell transplant.

Pulmonary nodules (PNs) develop frequently in patients with acute myeloid leukemia (AML). They are of infectious or inflammatory origin. They pose potential challenges to successful hematopoietic progenitor cell (HPC) transplant as they may be niches for infection reactivation or sites susceptible to subsequent infections. We retrospectively analyzed the outcome of 20 AML patients with multiple PNs who underwent allogeneic HPC transplants (12 related, 8 unrelated). There were 13 males and seven females (median age 52 yrs). Nine patients were in CR1, seven in CR2, and four with residual disease. The median times from appearance of PNs and from last positive CT scans to transplant were three and two months, respectively. The median time from pretransplant CT scans to transplant was one month. Multiple PNs were still reported in 5/20 of the pretransplant scans. The PNs in all five patients did not worsen after transplant. Four patients (one with positive pretransplant CT scan) died within the first 100 d after transplant, but none from primary pulmonary pathology. The median survival of this group of patients was 350 d. Our results, therefore, suggest that multiple PNs of uncertain etiology in patients with AML do not impact adversely on the outcome of allogeneic HPC transplant.

Peri-transplant clostridium difficile infections in patients undergoing allogeneic hematopoietic progenitor cell transplant.

Clostridium difficile infections (CDI) remain the leading cause of infectious diarrhea among hospitalized patients in this country. Patients with hematologic malignancies, especially those who undergo hematopoietic progenitor cell transplants are particularly at risk for developing CDI. One hundred and forty seven consecutive allogeneic hematopoietic progenitor cell transplants were analyzed for peri-transplant Clostridium difficile infections (PT-CDI). Sixteen patients (11%) developed PT-CDI (Median time = 7 days after transplant). The probability for developing PT-CDI during the peri-transplant period was 12.3%. History of CDI was strongly associated with the development of PT-CDI (P = 0.008) (OR = 5.48) (P = 0.017). These patients also developed PT-CDI much earlier than in those without a history (median 1 day vs. 8 days, P = 0.03). The probability for developing PT-CDI for those with a history was 39%. There was a trend toward significance (P = 0.065) between matched related donor grafts and the development of PT-CDI (OR = 0.245) (P = 0.08). Age, sex, diagnosis, transplant preparative regimens, Graft-versus-host disease (GVHD) prophylaxis, grade 3/4 acute GVHD, or use of antimicrobials within 8 weeks of transplant were not associated with PT-CDI. Non-CDI-related deaths occurred in one patient in the PT-CDI group and nine in the group without PT-CDI. In the remaining 139 patients, the length of hospital stay for those with PT-CDI was significantly longer than those without (mean 27 days vs. 22 days; P = 0.02).

Inferior outcome after allogeneic transplant in first remission in high-risk AML patients who required more than two cycles of induction therapy.

While some patients with high-risk acute myeloid leukemia (AML) require one or two cycles of induction chemotherapy to achieve a complete remission (CR), others require more than two cycles. We examined the outcomes of patients with high-risk AML who received allogeneic HPC transplant in CR1. Forty five consecutive high-risk AML patients in CR1 were included. All 45 patients had adverse cytogenetics, FLT 3 mutations, or secondary AML. Group A patients (n = 33) received one or two cycles, and Group B (n = 12) three or more cycles of induction chemotherapy. The patients were comparable in age, sex, white cell count at presentation, and time from diagnosis and from last chemotherapy to transplant. The 100-day mortality rate was higher in Group B patients (50% vs. 9%, P = 0.006). They had a higher non-relapse mortality (33% vs. 6%, P = 0.035) and a longer length of hospital stay from the day of stem cell infusion (median 21 vs. 20, P = 0.02; third quartile 22 vs. 28, P = 0.02). There was also a trend toward inferior event-free survival and overall survival. High-risk AML patients undergoing allogeneic transplant in CR1 after three or more cycles of induction chemotherapy have an inferior outcome and higher mortality when compared to those who only needed one or two cycles of induction chemotherapy. Novel strategies are needed to reduce the transplant-related mortality in high-risk AML patients needing more than two cycles of induction chemotherapy prior to allogeneic transplant in CR1.

Expressing gambling-related cognitive biases in motor behaviour: rolling dice to win prizes.

Cognitive perspectives on gambling propose that biased thinking plays a significant role in sustaining gambling participation and, in vulnerable individuals, gambling problems. One prominent set of cognitive biases include illusions of control involving beliefs that it is possible to influence random gaming events. Sociologists have reported that (some) gamblers believe that it is possible to throw dice in different ways to achieve gaming outcomes (e.g., 'dice-setting' in craps). However, experimental demonstrations of these phenomena are lacking. Here, we asked regular gamblers to roll a computer-simulated, but fair, 6 sided die for monetary prizes. Gamblers allowed the die to roll for longer when attempting to win higher value bets, and when attempting to hit high winning numbers. This behaviour was exaggerated in gamblers motivated to keep gambling following the experience of almost-winning in gambling games. These results suggest that gambling cognitive biases find expression in the motor behaviour of rolling dice for monetary prizes, possibly reflecting embodied substrates.

Sex differences in the cardiovascular effects of GnRH analogues.

The integral role of the hypothalamic-pituitary-gonadal axis in reproductive processes makes it a prime therapeutic target. By inhibiting sex steroid synthesis, gonadotropin-releasing hormone (GnRH) analogues are used in the management of cancers, benign neoplasms, infertility and gender dysphoria. However, the wide application of these therapeutics raises concerns regarding the unintended effects upon the cardiovascular system. In males with prostate cancer, GnRH analogues when used as an androgen deprivation therapy appear to increase the risk of cardiovascular disease, which is the leading cause of death in this population. Therefore, due to the utilisation of GnRH analogues across the lifespan and gender spectrum, this relationship merits discussion. Existing data suggest an association between GnRH analogues and major adverse cardiovascular events in males. Conversely, females receiving GnRH analogues for breast cancer treatment appear to be at an increased risk of developing hypertension. In this narrative review, we describe the uses of GnRH analogues in adults, adolescents and children. We discuss whether sex plays a role in the cardiovascular effects of GnRH analogues and explore the significance of sex hormone receptors in the vasculature. We also consider confounding factors such as malignancy, advanced age and infertility.

Multi-omic Analysis of Human B-cell Activation Reveals a Key Lysosomal BCAT1 Role in mTOR Hyperactivation by B-cell receptor and TLR9.

B-lymphocytes play major adaptive immune roles, producing antibody and driving T-cell responses. However, how immunometabolism networks support B-cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B-cell transcriptional, translational and metabolomic responses to B-cell receptor (BCR), Toll-like receptor 9 (TLR9), CD40-ligand (CD40L), interleukin-4 (IL4) or combinations thereof. T-independent BCR/TLR9 co-stimulation, which drives malignant and autoimmune B-cell states, jointly induced PD-L1 plasma membrane expression, supported by NAD metabolism and oxidative phosphorylation. BCR/TLR9 also highly induced the transaminase BCAT1, which localized to lysosomal membranes to support branched chain amino acid synthesis and mTORC1 hyperactivation. BCAT1 inhibition blunted BCR/TLR9, but not CD40L/IL4-triggered B-cell proliferation, IL10 expression and BCR/TLR pathway-driven lymphoma xenograft outgrowth. These results provide a valuable resource, reveal receptor-mediated immunometabolism remodeling to support key B-cell phenotypes including PD-L1 checkpoint signaling, and identify BCAT1 as a novel B-cell therapeutic target.

Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy.

BACKGROUND: Tumor expression of excision cross-complementing gene-1 (ERCC1), human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunit M1 (RRM1), and ribonucleotide reductase subunit M2 (RRM2), is associated with the efficacy of platinum and gemcitabine chemotherapy. The authors of this report recently demonstrated that high ERCC1 and RRM2 expression levels are independent negative prognostic markers for survival in early stage pancreas cancer. The differential expression and prognostic value of these biomarkers in biliary tract malignancy (BTM) is unknown. METHODS: In total, 63 patients who had tissue available for analysis were selected from a prospective database of all patients (n = 104) who underwent resection of BTM (intrahepatic, hilar, or distal cholangiocarcinoma; gallbladder carcinoma) between January 2000 and December 2008. Immunohistochemistry for ERCC1, hENT1, RRM1, and RRM2 expression was performed. Staining was scored by a single pathologist who was blinded to patient outcomes. RESULTS: The median patient age was 67 years. The median overall survival (OS) was 16.2 months, and the median follow-up was 32.7 months. Only 3 BTMs (4.8%) had high ERCC1 expression, and 92.1% and 81% of BTMs exhibited high hENT1 and RRM1 expression, respectively. RRM2 expression varied, and 32% of tumors demonstrated high RRM2 expression. ERCC1 and RRM1 were not associated with OS. High RRM2 expression was associated with a trend toward improved OS (30.8 months vs 16.2 months; P = .06), and high hENT1 expression was associated with improved OS (17.7 months vs 9.5 months; P = .04). CONCLUSIONS: Most BTMs exhibited low ERCC1 expression and high hENT1 and RRM1 expression, whereas RRM2 expression levels varied. High expression of hENT1 was associated with improved OS. These findings may have implications for the selection of chemotherapy agents (gemcitabine vs platinum) and the stratification of patients in chemotherapy trials that assess outcome.

Integrating sepsis management recommendations into clinical care guidelines for district hospitals in resource-limited settings: the necessity to augment new guidelines with future research.

Several factors contribute to the high mortality attributed to severe infections in resource-limited settings. While improvements in survival and processes of care have been made in high-income settings among patients with severe conditions, such as sepsis, guidelines necessary for achieving these improvements may lack applicability or have not been tested in resource-limited settings. The World Health Organization's recent publication of the Integrated Management of Adolescent and Adult Illness District Clinician Manual provides details on how to optimize management of severely ill, hospitalized patients in such settings, including specific guidance on the management of patients with septic shock and respiratory failure without shock. This manuscript provides the context, process and underpinnings of these sepsis guidelines. In light of the current deficits in care and the limitations associated with these guidelines, the authors propose implementing these standardized best practice guidelines while using them as a foundation for sepsis research undertaken in, and directly relevant to, resource-limited settings.

Nailfold video-capillaroscopy in the study of cardiovascular disease: a systematic review.

OBJECTIVES: Nailfold video-capillaroscopy (NVC) is an inexpensive method of assessing microcirculation. We reviewed the literature to assess whether changes to the nailfold capillaries exist in patients with cardiovascular disease (CVD). METHODS: We searched PubMed, Scopus and Cochrane Library databases for original research articles relating to the use of noninvasive microvascular assessment in patients with CVD. Methodological quality was assessed with the 'Quality Assessment Tool for Observational Cohort and Cross-sectional Studies.' The results obtained from NVC were analysed qualitatively and compared with other forms of microvascular assessment. RESULTS: In total 2759 articles were screened, of which 22 studies involving 562 patients (~40% women) with CVD were included. Mean age ranged between 3.7-68.4 years (cases) and 4.0-58.0 years (controls). Reduced capillary density and increased capillary dimensions were seen in patients with pulmonary arterial hypertension (PAH). Among patients with systemic sclerosis, advanced scleroderma patterns can be used to identify patients with or at risk of developing PAH. Functional nailfold changes precede structural changes in patients with hypertension. However, the studies were heterogeneous in the diagnosis of disease and the measurement of nailfold parameters. Most studies did not exclude conditions with altered nailfold features, and only one study performed a power calculation. Furthermore, abnormal nailfold findings are present in patients without systemic disease. CONCLUSIONS: Structural and functional changes to the nailfold are a feature of established CVD and precede the development of PAH. However, heterogeneity in measurement and abnormal findings in healthy participants limit their use in the wider population.

Factors affecting electrogram sensing in an insertable cardiac monitor: Insights from surface electrocardiogram mapping analysis.

BACKGROUND: Fidelity of electrogram sensing may reduce false alerts from an insertable cardiac monitor (ICM). OBJECTIVE: The purpose of this study was to assess the effect of vector length, implant angle, and patient factors on electrogram sensing using surface electrocardiogram (ECG) mapping. METHODS: Twelve separate precordial single-lead surface ECGs were acquired from 150 participants at 2 interelectrode distances (75 and 45 mm), at 3 vector angles (vertical, oblique, and horizontal), and in 2 postures (upright and supine). A subset of 50 patients also received a clinically indicated ICM implant in 1:1 ratio (Reveal LINQ [Medtronic, Minneapolis, MN]/BIOMONITOR III [Biotronik, Berlin, Germany]). All ECGs and ICM electrograms were analyzed by blinded investigators using DigitizeIt software (V2.3.3, Braunschweig, Germany). The P-wave visibility threshold was set at > 0.015 mV. Logistic regression was used to identify factors affecting P-wave amplitude. RESULTS: A total of 1800 tracings from 150 participants (44.5% [n = 68] female; median age 59 [35-73] years) were assessed. The median P- and R-wave amplitudes were 45% and 53% larger with vector lengths of 75 and 45 mm, respectively (P < .001 for both). The oblique orientation yielded the best P- and R-wave amplitudes, while posture change did not affect P-wave amplitude. Mixed effects modeling found that visible P-waves occur more frequently with a vector length of 75 mm than with 45 mm (86% vs 75%, respectively; P < .0001). A longer vector length improved both P-wave amplitude and visibility in all body mass index categories. There was a moderate correlation of P- and R-wave amplitudes from the ICM electrograms to those from surface ECG recordings (intraclass correlation coefficient 0.74 and 0.80, respectively). CONCLUSION: Longer vector length and oblique implant angle yielded the best electrogram sensing and are relevant considerations for ICM implantation procedures.