Rerandomization tests for analyzing correlated data from dental studies

Dental research studies often produce relatively small data sets in which observations are serially or spatially correlated. Rerandomization tests are presented as alternatives to analysis of variance and multivariate analysis for assessing group differences using such data. Rerandomization tests are particularly useful when the investigator is unwilling to make strong assumptions about the nature of the serial correlation or the distribution of the data. Two examples are discussed that demonstrate these techniques.     

Relative abundance,age structure,and body size in mudpuppy populations in southwestern Ontario

Little is known of mudpuppy (Necturus maculosus) population structure and ecology; some populations in the Great Lakes are thought to be in decline. Mudpuppies are the obligate hosts for the mudpuppy mussel (Simpsonaias ambigua), a species that is endangered in Canada and in many Great Lakes states. We surveyed mudpuppies from the Sydenham River, the only known Canadian locality of the mudpuppy mussel, in order to generate information on relative density, deformity rates and population age/size structure and used this information to compare them to known mudpuppy populations from Great Lakes sites in the Detroit River, Lake St. Clair and Long Point in Lake Erie. Deformity rates were elevated at some sites in the Sydenham River. The relative density of mudpuppies in the Sydenham River was lower than that of other Great Lakes sites and their age was skewed towards younger individuals. Although at lower densities than at other Great Lakes sites, the mudpuppy population in the Sydenham River appears stable and is showing signs of recruitment which bodes well for the future of the mudpuppy mussel population of the river.     

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.     

Hematopoietic Progenitors and the Bone Marrow Niche Shape the Inflammatory Response and Contribute to Chronic Disease

It is now well understood that the bone marrow (BM) compartment can sense systemic inflammatory signals and adapt through increased proliferation and lineage skewing. These coordinated and dynamic alterations in responding hematopoietic stem and progenitor cells (HSPCs), as well as in cells of the bone marrow niche, are increasingly viewed as key contributors to the inflammatory response. Growth factors, cytokines, metabolites, microbial products, and other signals can cause dysregulation across the entire hematopoietic hierarchy, leading to lineage-skewing and even long-term functional adaptations in bone marrow progenitor cells. These alterations may play a central role in the chronicity of disease as well as the links between many common chronic disorders. The possible existence of a form of “memory” in bone marrow progenitor cells is thought to contribute to innate immune responses via the generation of trained immunity (also called innate immune memory). These findings highlight how hematopoietic progenitors dynamically adapt to meet the demand for innate immune cells and how this adaptive response may be beneficial or detrimental depending on the context. In this review, we will discuss the role of bone marrow progenitor cells and their microenvironment in shaping the scope and scale of the immune response in health and disease.     

Rapid Discrimination of Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis Using Machine Learning on Infrared Spectra of Sera

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are both autoimmune inflammatory and demyelinating diseases of the central nervous system. NMOSD is a highly disabling disease and rapid introduction of the appropriate treatment at the acute phase is crucial to prevent sequelae. Specific criteria were established in 2015 and provide keys to distinguish NMOSD and MS. One of the most reliable criteria for NMOSD diagnosis is detection in patient’s serum of an antibody that attacks the water channel aquaporin-4 (AQP-4). Another target in NMOSD is myelin oligodendrocyte glycoprotein (MOG), delineating a new spectrum of diseases called MOG-associated diseases. Lastly, patients with NMOSD can be negative for both AQP-4 and MOG antibodies. At disease onset, NMOSD symptoms are very similar to MS symptoms from a clinical and radiological perspective. Thus, at first episode, given the urgency of starting the anti-inflammatory treatment, there is an unmet need to differentiate NMOSD subtypes from MS. Here, we used Fourier transform infrared spectroscopy in combination with a machine learning algorithm with the aim of distinguishing the infrared signatures of sera of a first episode of NMOSD from those of a first episode of relapsing-remitting MS, as well as from those of healthy subjects and patients with chronic inflammatory demyelinating polyneuropathy. Our results showed that NMOSD patients were distinguished from MS patients and healthy subjects with a sensitivity of 100% and a specificity of 100%. We also discuss the distinction between the different NMOSD serostatuses. The coupling of infrared spectroscopy of sera to machine learning is a promising cost-effective, rapid and reliable differential diagnosis tool capable of helping to gain valuable time in patients’ treatment.     

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

Immunotherapy using chimeric antigen receptor (CAR) T cells is a rapidly emerging modality that engineers T cells to redirect tumor-specific cytotoxicity. CAR T cells have been well characterized for their efficacy against B cell malignancies, and rigorously studied in other types of tumors. Preclinical evaluation of CAR T cell function, including direct tumor killing, cytokine production, and memory responses, is crucial to the development and optimization of CAR T cell therapies. Such comprehensive examinations are usually performed in different types of models. Model establishment should focus on key challenges in the clinical setting and the capability to generate reliable data to indicate CAR T cell therapeutic potency in the clinic. Further, modeling the interaction between CAR T cells and tumor microenvironment provides additional insight for the future endeavors to enhance efficacy, especially against solid tumors. This review will summarize both in vitro and in vivo models for CAR T cell functional evaluation, including how they have evolved with the needs of CAR T cell research, the information they can provide for preclinical assessment of CAR T cell products, and recent technology advances to test CAR T cells in more clinically relevant models.     

Reliability and validity of a demand curve measure of alcohol reinforcement.

Recent clinical research suggests that several self-report behavioral economic measures of relative reinforcing efficacy (RRE) may show utility as indices of substance abuse problem severity. The goal of the present study was to evaluate the reliability and validity of the Alcohol Purchase Task (APT), a RRE measure that uses hypothetical choices regarding alcohol purchases at varying prices (demand curves) to generate several indices of alcohol-related reinforcement. Participants were 38 college students who reported recent alcohol consumption. Both the raw alcohol purchase/consumption values and several of the computed reinforcement parameters (intensity & Omax) showed good to excellent 2-week test–retest reliability. Reinforcement parameters derived from both a linear-elasticity (Hursh, Raslear, Bauman, & Black, 1989) and an exponential (Hursh & Silberberg, 2008) demand curve equation were generally less reliable, despite the fact that both equations provided a good fit to participants’ reported consumption data. The APT measures of demand intensity (number of drinks consumed when price = 0), Omax (maximum expenditure), and elasticity (α) were correlated with weekly drinking, alcohol-related problems, and other self-report RRE measures (relative discretionary monetary expenditures toward alcohol and/or relative substance-related activity participation and enjoyment). Demand intensity was uniquely associated with problem drinking in a regression model that controlled for weekly consumption. These results provide support for the reliability and validity of the RRE indices generated with the APT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bandwidth allocation in Diffserv-enabled ethernet passive optical networks

Ethernet passive optical networks (EPONs) have attracted considerable attention from the industry, as they offer a simple, highly flexible and cost-effective solution to the problem of providing broadband access to a customer. The authors present a new approach to bandwidth allocation in EPONs where the optical line terminator (OLT) has full control over the access mechanism. This results in much simpler optical network unit (ONU) architecture. It is shown that such an OLT-centric architecture offers full support for differentiated services and makes enforcement of service level agreements possible. Extensive simulation experiments show that bandwidth allocation algorithms deployed in such a centralised environment can deliver good performance in terms of average and maximum packet delay. The authors introduce two new algorithms that target SLA-aware EPONs and provide a good protection of offered quality of service against interference from other sources.     

Behavior therapy for Tourette's disorder: Utilization in a community sample and an emerging area of practice for psychologists.

The current article describes the phenomenology and empirically supported treatments for Tourette's disorder (TD) and presents data on treatment utilization from two separate national surveys of adults with TD (N = 672) and parents of children with TD (N = 740). Despite a wealth of empirical evidence demonstrating its effectiveness, results suggest that most people with TD do not receive behavior therapy for the condition. Reasons for this include a lack of information about the disorder among consumers and providers, a shortage of providers trained in the treatment, and concern about possible negative effects of behavioral treatment. The article concludes with a discussion about dissemination efforts aimed at making behavior therapy more widely available to children and adults with chronic tics and a review of beliefs about the negative effects of behavior therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of pigment on biodeterioration of acrylic paint films in Southern Brazil

Biodeterioration of paint films leads to loss of durability and increased repainting costs. The influence of pigments on the biodeterioration of architectural paint films in the city of Florianópolis, Brazil, was evaluated using ten differently colored acrylic paint films exposed to the environment for 34 months. Fouling (biofilm formation) on the surfaces was assessed macroscopically, using British Standard BS 3900/1989 G6, and microscopically. After 20 months, major colonizers were bacteria and fungi, with some cyanobacteria and few algae; north-facing suede and peach and south-facing ice colors showed 100% cover at this time. The least affected color at all times was blue, with a maximum of 30% cover on south-facing panels after 34 months. North-facing panels were generally more fouled than South-facing. Blue, red, and ceramic colors always performed best. Resistance to fouling may have been due to copper in blue and acidity from sulfur oxides in ceramic pigments. Pigments may prolong paint film life and reduce the need for biocides.