Nevin Manimala

Stat Med. 2022 Nov 25. doi: 10.1002/sim.9610. Online ahead of print.

ABSTRACT

The need to model a cure fraction, the proportion of a cohort not susceptible to the event of interest, arises in a variety of contexts including tumor relapse in oncology. Existing methodology assumes that follow-up is long enough for all uncured subjects to have experienced the event of interest at the time of analysis, and researchers have demonstrated that fitting cure models without sufficient follow-up leads to bias. Few statistical methods exist to evaluate sufficient follow-up, and they can exhibit poor performance and lead users to falsely conclude sufficient follow-up, leading to bias, or to falsely claim insufficient follow-up, possibly leading to additional, costly data collection. We propose a new quantitative statistic (RECeUS) to evaluate whether cure models may be appropriate to apply to censored data. Specifically, we propose that the estimated proportion of censored uncured subjects in a study can be used to evaluate cure model appropriateness. We evaluated the performance of RECeUS against existing methods via simulation and with two data examples, and we observe that RECeUS displays superior performance. In simulated and real-world settings, RECeUS correctly identifies both situations in which data appear appropriate for cure modeling and when data seem inappropriate for fitting cure models.

PMID:36433635 | DOI:10.1002/sim.9610

Int J Biostat. 2022 Nov 28. doi: 10.1515/ijb-2022-0047. Online ahead of print.

ABSTRACT

With our increased ability to capture large data, causal inference has received renewed attention and is playing an ever-important role in biomedicine and economics. However, one major methodological hurdle is that existing methods rely on many unverifiable model assumptions. Thus robust modeling is a critically important approach complementary to sensitivity analysis, where it compares results under various model assumptions. The more robust a method is with respect to model assumptions, the more worthy it is. The doubly robust estimator (DRE) is a significant advance in this direction. However, in practice, many outcome measures are functionals of multiple distributions, and so are the associated estimands, which can only be estimated via U-statistics. Thus most existing DREs do not apply. This article proposes a broad class of highly robust U-statistic estimators (HREs), which use semiparametric specifications for both the propensity score and outcome models in constructing the U-statistic. Thus, the HRE is more robust than the existing DREs. We derive comprehensive asymptotic properties of the proposed estimators and perform extensive simulation studies to evaluate their finite sample performance and compare them with the corresponding parametric U-statistics and the naive estimators, which show significant advantages. Then we apply the method to analyze a clinical trial from the AIDS Clinical Trials Group.

PMID:36433631 | DOI:10.1515/ijb-2022-0047

Med Phys. 2022 Nov 25. doi: 10.1002/mp.16125. Online ahead of print.

ABSTRACT

Studies of skeletal metabolism using measurements of bone metabolic flux (K_i ) obtained with [¹⁸ F] sodium fluoride ([¹⁸ F]NaF) positron emission tomography (PET) scans have been used in clinical research for the last 30 years. The technique has proven useful as an imaging biomarker in trials of novel drug treatments for osteoporosis and investigating other metabolic bone diseases, including chronic kidney disease mineral and bone disorder. It has also been shown to be valuable in metastatic bone disease in breast cancer patients and may have potential in other cancer types, such as prostate cancer, to assess early bone fracture risk. However, these studies have usually required a 60-min dynamic PET scan and measurement of the arterial input function (AIF), making them difficult to translate into the clinic for diagnostic purposes. We have previously proposed a simplified method that estimates the K_i value at an imaging site from a short (4-min) static scan and venous blood samples. A key advantage of this method is that, by acquiring a series of static scans, values of K_i can be quickly measured at multiple sites using a single injection of the tracer. To date, the widespread use of [¹⁸ F]NaF PET has been limited by the need to measure the AIF required for the mathematical modeling of tracer kinetics to derive K_i and other kinetic parameters. In this report, we review different methods of measuring the AIF, including direct arterial sampling, the use of a semi-population input function (SP-AIF), and image-derived input function, the latter two requiring only two or three venous blood samples obtained between 30 and 60 min after injection. We provide an SP-AIF model and a spreadsheet for calculating K_i values using the static scan method that others can use to study bone metabolism in metabolic and metastatic bone diseases without requiring invasive arterial blood sampling. The method shortens scan times, simplifies procedures and reduces the cost of multi-center trials without losing accuracy or precision. This article is protected by copyright. All rights reserved.

PMID:36433629 | DOI:10.1002/mp.16125

Sensors (Basel). 2022 Nov 21;22(22):9014. doi: 10.3390/s22229014.

ABSTRACT

Line-of-sight (LOS) indoor optical wireless communications (OWC) enable a high data rate transmission while potentially suffering from optical channel obstructions. Additional LOS links using diversity techniques can tackle the received signal performance degradation, where channel gains often differ in multiple LOS channels. In this paper, a novel active transmitter detection scheme in spatial modulation (SM) is proposed to be incorporated with signal space diversity (SSD) technique to enable an increased OWC system throughput with an improved bit-error-rate (BER). This transmitter detection scheme is composed of a signal pre-distortion technique at the transmitter and a power-based statistical detection method at the receiver, which can address the problem of power-based transmitter detection in SM using carrierless amplitude and phase modulation waveforms with numerous signal levels. Experimental results show that, with the proposed transmitter detection scheme, SSD can be effectively provided with ~0.61 dB signal-to-noise-ratio (SNR) improvement. Additionally, an improved data rate ~7.5 Gbit/s is expected due to effective transmitter detection in SM. The SSD performances at different constellation rotation angles and under different channel gain distributions are also investigated, respectively. The proposed scheme provides a practical solution to implement power-based SM and thus aids the SSD realization for improving system performance.

PMID:36433606 | DOI:10.3390/s22229014

Sensors (Basel). 2022 Nov 21;22(22):8998. doi: 10.3390/s22228998.

ABSTRACT

OBJECTIVE: Quality of intraoperative teamwork may have a direct impact on patient outcomes. Heart rate variability (HRV) synchrony may be useful for objective assessment of team cohesion and good teamwork. The primary aim of this study was to investigate the feasibility of using HRV synchrony in surgical teams. Secondary aims were to investigate the association of HRV synchrony with length of procedure (LOP), complications, number of intraoperative glitches and length of stay (LOS). We also investigated the correlation between HRV synchrony and team familiarity, pre- and intraoperative stress levels (STAI questionnaire), NOTECHS score and experience of team members.

METHODS: Ear, nose and throat (ENT) and vascular surgeons (consultant and registrar team members) were recruited into the study. Baseline demographics including level of team members’ experience were gathered before each procedure. For each procedure, continuous electrocardiogram (ECG) recording was performed and questionnaires regarding pre- and intraoperative stress levels and non-technical skills (NOTECHS) scores were collected for each team member. An independent observer documented the time of each intraoperative glitch. Statistical analysis was conducted using stepwise multiple linear regression.

RESULTS: Four HRV synchrony metrics which may be markers of efficient surgical collaboration were identified from the data: 1. number of HRV synchronies per hour of procedure, 2. number of HRV synchrony trends per hour of procedure, 3. length of HRV synchrony trends per hour of procedure, 4. area under the HRV synchrony trend curve per hour of procedure. LOP was inversely correlated with number of HRV synchrony trends per hour of procedure (p < 0.0001), area under HRV synchrony trend curve per hour of procedure (p = 0.001), length of HRV synchrony trends per hour of procedure (p = 0.002) and number of HRV synchronies per hour of procedure (p < 0.0001). LOP was positively correlated with: FS (p = 0.043; R = 0.358) and intraoperative STAI score of the whole team (p = 0.007; R = 0.493).

CONCLUSIONS: HRV synchrony metrics within operating teams may be used as an objective marker to quantify surgical teamwork. We have shown that LOP is shorter when the intraoperative surgical teams’ HRV is more synchronised.

PMID:36433593 | DOI:10.3390/s22228998

Sensors (Basel). 2022 Nov 20;22(22):8988. doi: 10.3390/s22228988.

ABSTRACT

Biometrics is a critical component of cybersecurity that identifies persons by verifying their behavioral and physical traits. In biometric-based authentication, each individual can be correctly recognized based on their intrinsic behavioral or physical features, such as face, fingerprint, iris, and ears. This work proposes a novel approach for human identification using 3D ear images. Usually, in conventional methods, the probe image is registered with each gallery image using computational heavy registration algorithms, making it practically infeasible due to the time-consuming recognition process. Therefore, this work proposes a recognition pipeline that reduces the one-to-one registration between probe and gallery. First, a deep learning-based algorithm is used for ear detection in 3D side face images. Second, a statistical ear model known as a 3D morphable ear model (3DMEM), was constructed to use as a feature extractor from the detected ear images. Finally, a novel recognition algorithm named you morph once (YMO) is proposed for human recognition that reduces the computational time by eliminating one-to-one registration between probe and gallery, which only calculates the distance between the parameters stored in the gallery and the probe. The experimental results show the significance of the proposed method for a real-time application.

PMID:36433582 | DOI:10.3390/s22228988

J Med Virol. 2022 Nov 25. doi: 10.1002/jmv.28350. Online ahead of print.

ABSTRACT

Human Endogenous Retroviruses (HERVs) are viral sequences integrated into the human genome, resulting from the infection of human germ-line cells by ancient exogenous retroviruses. Despite losing their replication and retrotransposition abilities, HERVs appear to have been co-opted in human physiological functions while their aberrant expression is linked to human disease. The role of HERVs in multiple malignancies has been demonstrated, however, the extent to which HERV activation and expression participate in the development of cancer is not yet fully comprehended. In this review article, we discuss the presumed role of HERVs in carcinogenesis and their promising diagnostic and prognostic implications. Additionally, we explore recent data on the HERVs in cancer therapeutics, either through the manipulation of their expression, to induce anti-tumor innate immunity responses or as cancer immunotherapy targets. Finally, more precise and higher resolution high-throughput sequencing approaches will further elucidate HERV participation in human physiological and pathological processes. This article is protected by copyright. All rights reserved.

PMID:36428242 | DOI:10.1002/jmv.28350

Stat Med. 2022 Nov 25. doi: 10.1002/sim.9594. Online ahead of print.

ABSTRACT

There is a growing medical interest in combining several agents and optimizing their dosing schedules in a single trial in order to optimize the treatment for patients. Evaluating at doses of several drugs and their scheduling in a single Phase I trial simultaneously possess a number of statistical challenges, and specialized methods to tackle these have been proposed in the literature. However, the uptake of these methods is slow and implementation examples of such advanced methods are still sparse to date. In this work, we share our experience of proposing a model-based partial ordering continual reassessment method (POCRM) design for three-dimensional dose-finding in an oncology trial. In the trial, doses of two agents and the dosing schedule of one of them can be escalated/de-escalated. We provide a step-by-step summary on how the POCRM design was implemented and communicated to the trial team. We proposed an approach to specify toxicity orderings and their a-priori probabilities, and developed a number of visualization tools to communicate the statistical properties of the design. The design evaluation included both a comprehensive simulation study and considerations of the individual trial behavior. The study is now enrolling patients. We hope that sharing our experience of the successful implementation of an advanced design in practice that went through evaluations of several health authorities will facilitate a better uptake of more efficient methods in practice.

PMID:36428217 | DOI:10.1002/sim.9594

Br J Oral Maxillofac Surg. 2022 Oct 4:S0266-4356(22)00271-6. doi: 10.1016/j.bjoms.2022.09.008. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the prognostic significance of dysplasia in patients undergoing primary surgery with curative intent in the treatment of oral squamous cell carcinoma (OSCC). This study specifically aimed to demonstrate the effect of dysplasia on local recurrence, disease specific survival (DSS) and overall survival (OS). Data collection for 833 patients with OSCC undergoing treatment for curative intent was undertaken retrospectively for the period of February 2006 to May 2020. Analysis of any association between known clinicopathological prognostic categorical variables with respect to dysplasia was undertaken using the chi squared test. A Kaplan-Meier analysis was performed to demonstrate the impact of dysplasia on DSS and OS, and Cox’s proportional-hazards model deployed to obtain hazard ratios associated with dysplasia and the outcomes of interest. Dysplasia was statistically significant in predicting disease specific and overall survival in patients undergoing primary surgery for OSCC (DSS p<0.001, HR 0.577; 95%CI 0.428 to 0.777), OS p<0.001 HR 0.691; 95%CI 0.562 to 0.850) with the absence of dysplasia predicting poorer outcomes. The absence of dysplasia correlated with pathological higher T and N stage, increased categorised depth of tumour invasion, non-cohesive invasive front, lymphovascular invasion, perineural invasion, extranodal extension and increased modified Glasgow Prognostic Score. No significant prognostic relationship was attributable to the presence of dysplasia at a surgical margin. The absence of dysplasia appeared to be a significant independent prognostic indicator for patients with OSCC. The presence or absence of dysplasia may provide a heuristic means of stratifying OSCC primary lesions in terms of disease hostility.

PMID:36428155 | DOI:10.1016/j.bjoms.2022.09.008

Injury. 2022 Nov 1:S0020-1383(22)00802-6. doi: 10.1016/j.injury.2022.10.031. Online ahead of print.

ABSTRACT

INTRODUCTION: Concomitant patellar tendon (PT) tear with cruciate or multi-ligament knee injuries (MLKI) following high-velocity injury requires a systematic approach.

METHODS: The study is a retrospective case series of patients (2008-2019) with concomitant PT ligament injury with cruciate or collateral ligament injury (MLKI), including bony avulsion injuries. Isolated cruciate and MLKI without patellar tendon tears are excluded. N = 32 patients (1 female and 31 male) are divided into two groups, Group 1 (11 patients) with PT tear and ACL tear and group 2 (21 patients) with PT tear and MLKIs. Patients were taken up for a single stage in types 1,2,3 and staged repair with reconstruction for types 4,5 of our new classification. All the patients are followed up regularly, and IKDC and Lyshom’s score and objective radiological stress x-rays taken at each follow-up RESULTS: Incidence of PTT combined injuries among all knee ligament injuries is 0.57%. The mean age was 35.09+/-11.96 SD(group1) and 36.55+/-11.89 SD(group2). The average follow-up was 34.45 months +/- 12.86SD (group 1) and 35.3 months +/- 15.75 SD (group2). Mean post-operative Lysholm score and IKDC score of group 1 and group 2 improvement was statistically significant p-value <=0.01. The mean post-operative ROM of the two groups were 132.73 (SD 6.46) (Group 1) and 111.75 (15.75) (Group 2) and was a statistically significant p-value <0.01. Residual lag of 30^° seen in all patients improved by 3rd month in group 1 and 6th month in group 2. Knee stiffness is seen in 2 patients and superficial infection in 2 patients.

CONCLUSION: PTT combined injuries are rare and occurs due to direct impact injuries. Single-stage PT repair with ACL reconstruction gives adequate stability, and extensor lag is eminent and needs supervised rehabilitation. PT with MLKI is a challenging scenario that can be performed in single-stage/multiple stages, depending on the injuries, surgical expertise, and institutional facilities. Newer simplified classification aids surgeons in planning a treatment strategy.

PMID:36428146 | DOI:10.1016/j.injury.2022.10.031