The conscious perception of the hedonic sensory properties of caloric foods is commonly believed to guide our dietary choices. Current and traditional models implicate the consciously perceived hedonic qualities of food as driving overeating, whereas subliminal signals arising from the gut would curb our uncontrolled desire for calories. Here we review recent animal and human studies that support a markedly different model for food reward. These findings reveal in particular the existence of subcortical body-to-brain neural pathways linking gastrointestinal nutrient sensors to the brain's reward regions. Unexpectedly, consciously perceptible hedonic qualities appear to play a less relevant, and mostly transient, role in food reinforcement. In this model, gut-brain reward pathways bypass cranial taste and aroma sensory receptors and the cortical networks that give rise to flavor perception. They instead reinforce behaviors independently of the cognitive processes that support overt insights into the nature of our dietary decisions. Expected final online publication date for the Annual Review of Psychology, Volume 71 is January 4, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Health care involves the participation of patients, family, and a diverse team of often highly specialized health care professionals. Involvement of all these team members in a cooperative and coordinated way is essential to providing exceptional care. This article introduces key concepts relating to interprofessional collaborative teamwork. Approaches to measuring and studying collaboration and evidence demonstrating the benefits of collaboration are presented. The structural, psychological, and educational factors which may determine collaborative behaviour are described. LEARNING OBJECTIVES: By the end of this CME article, participants will be able to 1. Distinguish between multifunctional and interdisciplinary teams, 2. Define collaboration in a health care setting, 3. Describe the value of collaboration to patients, staff, and organizations, 4. Understand approaches to measuring collaboration, and 5. Identify factors that determine the ability of teams to collaborate. This article is a CME article and provides the equivalent of 2 hours of continuing education that may be applied to your professional development credit system. A 20-question multiple choice quiz follows this reading, and answers can be found on page 216. Please note that no formalized credit (Category A) is available from CAMRT.

Synaptic plasticity, the activity-dependent change in neuronal connection strength, has long been considered an important component of learning and memory. Computational and engineering work corroborate the power of learning through the directed adjustment of connection weights. Here we review the fundamental elements of four broadly categorized forms of synaptic plasticity and discuss their functional capabilities and limitations. Although standard, correlation-based, Hebbian synaptic plasticity has been the primary focus of neuroscientists for decades, it is inherently limited. Three-factor plasticity rules supplement Hebbian forms with neuromodulation and eligibility traces, while true supervised types go even further by adding objectives and instructive signals. Finally, a recently discovered hippocampal form of synaptic plasticity combines the above elements, while leaving behind the primary Hebbian requirement. We suggest that the effort to determine the neural basis of adaptive behavior could benefit from renewed experimental and theoretical investigation of more powerful directed types of synaptic plasticity. Expected final online publication date for the Annual Review of Neuroscience, Volume 43 is July 8, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Babesiosis, caused by piroplasmid protozoans in the genus Babesia, is arguably the most important vector-borne disease of livestock and companion animals and is growing in importance as a zoonosis. Ixodid ticks were identified as vectors more than a hundred years ago, but the particular tick species transmitting some significant pathogens are still unknown. Moreover, it is only recently that the complexity of the pathogen-tick relationship has been revealed as a result of studies enabled by gene expression and RNA interference methodology. In this article, we provide details of demonstrated and incriminated vectors, maps of the current knowledge of vector distribution, a summary of established features of the pathogen life cycle in the vector, and an outline of molecular research on pathogen-tick relationships. The article concludes with a discussion of vector ecology and disease epidemiology in a global-change context and with suggestions for future research. Expected final online publication date for the Annual Review of Entomology Volume 64 is January 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The ELR(+) chemokine CXCL15, which recruits neutrophils during pulmonary inflammation, is also known as lungkine due to its reported exclusive expression in the lung. We now report that CXCL15 mRNA and protein are also expressed in other mucosal and endocrine organs including the gastrointestinal and urogenital tracts and the adrenal gland. Our results indicate that CXCL15 is expressed throughout the gastrointestinal tract, with the exception of the cecum. Gastric CXCL15 protein expression is approximately 10-fold lower than pulmonary expression and primarily occurs in a specific lineage of gastric epithelial cells, the prezymogenic and zymogenic cell. Similar to the increased expression of CXCL15 during pulmonary inflammation, gastric inflammation induced by infection with Helicobacter felis caused an increase in gastric CXCL15 expression. However, colonic CXCL15 expression was not altered in two different models of colonic inflammation, the Helicobacter hepaticus T-cell transfer model and the mdr1a(-/-) model of colitis. These findings clearly demonstrate that CXCL15, previously reported to be the only lung-specific chemokine, is also highly expressed in other murine mucosal and endocrine organs. The functional role of CXCL15 in mucosal disease remains to be elucidated. This manuscript contains online supplemental material at (http://www.jhc.org). Please visit this article online to view these materials.

Cranial placodes contribute to many sensory organs and ganglia of the vertebrate head. The olfactory, otic, and lateral line placodes form the sensory receptor cells and neurons of the nose, ear, and lateral line system; the lens placode develops into the lens of the eye; epibranchial, profundal, and trigeminal placodes contribute sensory neurons to cranial nerve ganglia; and the adenohypophyseal placode gives rise to the anterior pituitary, a major endocrine control organ. Despite these differences in fate, all placodes are now known to originate from a common precursor, the preplacodal ectoderm (PPE). The latter is a horseshoe-shaped domain of ectoderm surrounding the anterior neural plate and neural crest and is defined by expression of transcription factor Six1, its cofactor Eya1, and other members of the Six and Eya families. Studies in zebrafish, Xenopus, and chick reveal that the PPE is specified together with other ectodermal territories (epidermis, neural crest, and neural plate) during early embryogenesis. During gastrulation, domains of ventrally (e.g., Dlx3/Dlx5, GATA2/GATA3, AP2, Msx1, FoxI1, and Vent1/Vent2) and dorsally (e.g., Zic1, Sox3, and Geminin) restricted transcription factors are established in response to a gradient of BMP and help to define non-neural and neural competence territories, respectively. At neural plate stages, the PPE is then induced in the non-neural competence territory by signals from the adjacent neural plate and mesoderm including FGF, BMP inhibitors, and Wnt inhibitors. Subsequently, signals from more localized signaling centers induce restricted expression domains of various transcription factors within the PPE, which specify multiplacodal areas and ultimately individual placodes. For further resources related to this article, please visit the WIREs website.

BACKGROUND

The author has declared no conflicts of interest for this article.

A wide range of behavioral and cognitive techniques have been found to be efficacious for helping children to cope with acute pain. Research into the clinical applicability of these interventions is at an early stage but increasingly is being recognized as an important future direction. Many existing interventions and assessment tools are reasonably easy to use, allowing practitioners to have the tools to identify children most vulnerable to pain and to significantly reduce pain-related distress in these children. For additional information from the Internet, please visit the UCLA Pediatric Pain Program Web site: http:¿members.xoom.com/UCLAPAIN/.

Two experiments investigated whether the spatial reference directions that are used to specify objects' locations in memory can be solely determined by layout geometry. Participants studied a layout of objects from a single viewpoint while their eye movements were recorded. Subsequently, participants used memory to make judgments of relative direction (e.g., "Imagine you are standing at X, facing Y, please point to Z"). When the layout had a symmetric axis that was different from participants' viewing direction, the sequence of eye fixations on objects during learning and the preferred directions in pointing judgments were both determined by the direction of the symmetric axis. These results provide further evidence that interobject spatial relations are represented in memory with intrinsic frames of reference.

Realizing the decoding of brain signals into control commands, brain-computer interfaces (BCI) aim to establish an alternative communication pathway for locked-in patients. In contrast to most visual BCI approaches which use event-related potentials (ERP) of the electroencephalogram, auditory BCI systems are challenged with ERP responses, which are less class-discriminant between attended and unattended stimuli. Furthermore, these auditory approaches have more complex interfaces which imposes a substantial workload on their users. Aiming for a maximally user-friendly spelling interface, this study introduces a novel auditory paradigm: "CharStreamer". The speller can be used with an instruction as simple as "please attend to what you want to spell". The stimuli of CharStreamer comprise 30 spoken sounds of letters and actions. As each of them is represented by the sound of itself and not by an artificial substitute, it can be selected in a one-step procedure. The mental mapping effort (sound stimuli to actions) is thus minimized. Usability is further accounted for by an alphabetical stimulus presentation: contrary to random presentation orders, the user can foresee the presentation time of the target letter sound. Healthy, normal hearing users (n = 10) of the CharStreamer paradigm displayed ERP responses that systematically differed between target and non-target sounds. Class-discriminant features, however, varied individually from the typical N1-P2 complex and P3 ERP components found in control conditions with random sequences. To fully exploit the sequential presentation structure of CharStreamer, novel data analysis approaches and classification methods were introduced. The results of online spelling tests showed that a competitive spelling speed can be achieved with CharStreamer. With respect to user rating, it clearly outperforms a control setup with random presentation sequences.

Motor-vehicle crashes are a leading cause of death among teenagers and in many instances appear linked to negative peer influences on adolescent driving behavior. This article examines a range of developmental and structural factors that potentially increase the risks associated with adolescent driving. Developmental risk factors for adolescents include a propensity toward engaging in deviant and risky behavior, a desire to please peers, and the potential cost to an adolescent of alienating peers with his or her behavior while driving. Structural features of the driving situation that create risks for negative peer influences on driving behavior include the inability of adolescents to look at peers who may be pressuring them, divided attention, the need to behave in a conventional manner among peers who may not value conventional behavior, and the lack of accountability by peers for the effects of any risky driving they promote. A range of potential peer influences are considered, including passive and active distraction and direct disruption of driving, as well as more positive influences, such as peer modeling of good driving behavior and positive reinforcement of good driving. Although the range of risk factors created by peers is large, this range presents a number of promising targets for intervention to improve teen driving safety.

OBJECTIVE

to examine women's attitudes to being questioned by their midwife, during and after pregnancy, about exposure to violence.

METHODS

an explorative study using content analysis of one open-ended question.

METHODS

all antenatal clinics in Uppsala, a medium-sized Swedish university town.

METHODS

all women registered for antenatal care before 32 weeks of pregnancy, during a period of 6 months.

METHODS

all women were assessed regarding abuse, using the Abuse Assessment Screen (McFarlane 1993) twice during pregnancy and once again more than four weeks after the birth. On the last occasion the women were asked to respond to an open-ended written question worded: 'Please describe how you felt about being questioned by your midwife at the antenatal clinic concerning violence' Those women who reported violence and those who did not were compared regarding their attitude to being asked about violence.

RESULTS

879 women were presented with the open-ended question. Eighty per cent found the questioning acceptable, 12% neither acceptable nor unacceptable, 5% both acceptable and unacceptable, and only 3% found it unacceptable. There was no difference between those who reported abuse and those who did not, as to whether the questioning was unacceptable.

CONCLUSIONS

the findings suggest that most pregnant women are not averse to being asked, by their midwife, about exposure to violence. As part of the identification of risk factors that is carried out in every pregnancy, the midwife should ask about exposure to violence at the antenatal clinic. To feel confident when raising the subject of abuse, midwives must be taught about the nature of intimate-partner violence, and appropriate referral and intervention strategies.

When children wheeze Would no one please provide their medicine blindly: for this might ease their young demise and that would be unkindly. Excessive use of salbutamol inhalers is described in two young people with asthma, a girl and a boy both aged 15 years. These cases and others quoted indicate that dependence on pressurized aerosol bronchodilators can and does occur in young people. Known side-effects of salbutamol are described. Where over-usage occurs a state of diminished airways response seems to result: it is also possible that the convulsions which occurred in one case may be related to such abuse. Responsibility for the provision and use of these inhalers in young people is discussed and suggestions made towards their greater control.

The processing of sensory information is fundamental to the basic operation of the nervous system. Our nervous system uses this sensory information to gain knowledge of our bodies and the world around us. This knowledge is of great importance as it provides the coherent and accurate information necessary for successful motor control. Yet, all this knowledge is of an uncertain nature because we obtain information only through our noisy sensors. We are thus faced with the problem of integrating many uncertain pieces of information into estimates of the properties of our bodies and the surrounding world. Bayesian approaches to estimation formalize the problem of how this uncertain information should be integrated. Utilizing this approach, many studies make predictions that faithfully predict human sensorimotor behavior. WIREs Cogni Sci 2011 2 419-428 DOI: 10.1002/wcs.125 For further resources related to this article, please visit the WIREs website.

OBJECTIVE

To describe feminine hygiene practices and douching behavior in adolescent women.

METHODS

A cross-sectional anonymous survey.

METHODS

Adolescents (majority rural) admitted to a correctional institution for girls.

METHODS

Description of feminine hygiene practices, prevalence of vaginal douching, types of substances used, reported reasons for, and timing of douching.

RESULTS

In a period of 16 weeks, 104 girls were surveyed within a week of admission. The mean age was 15.4 (SD 1.5; range 12-18) yr, and age at sexual debut 13.1 (SD 1.4) yr. Use of feminine hygiene products was reported by: 9% for feminine suppository, 33% towelettes, 40% spray, 67% feminine wash; only 18% reported no use of those feminine hygiene products listed. A history of ever having douched was reported by 79%; the mean first douching age was 14.0 (SD 1.3; range 11-16). Douching product users were significantly more likely to know someone who douches regularly (P <.0001) and have watched douche commercials (P =.0001) than those who did not douche. A majority used store-bought products, vinegar in water and scented solution being the most popular; baking soda, Betadine, Pine-sol, and Lysol were other products used. Commonly cited reasons for douching included to feel good and fresh (60%), and to rid of odor and of blood (47% each). Other reasons cited were to please partner (12%) and to avoid going to a doctor (6%). Timing of douching included: after period (69%), after sex (52%), before sex (16%), before going to a doctor (17%). Among those who douched, 51% douched once a month, and an additional 32% more often than that.

CONCLUSIONS

This study provides troublesome findings regarding the feminine hygiene practices of mostly rural southern teenagers who have been incarcerated.

OBJECTIVE

To identify problems in how medical school faculty are evaluated, from the perspectives of faculty and administrators, and to understand how perceptions of the problems differ among those with varying roles within the medical school.

METHODS

In March 1992 seven copies of an open-ended questionnaire were sent to each dean at the 126 accredited U.S. medical schools and 16 affiliated Canadian schools. The deans were instructed to complete one form themselves and to distribute one copy each to (1) a faculty affairs dean, (2) a basic science chair, (3) a clinical chair, (4) a member of chair of the school's promotion and tenure committee, (5) a senior faculty member, and (6) a junior faculty member. The authors conducted a content analysis of narrative comments in response to a question that began "Please identify and briefly describe the most salient problems you observe at your institution in how faculty are evaluated."

RESULTS

Of a possible 994 responses, 455 (46%) were received. The respondents were from 102 of the 126 U.S. medical schools (81%) and eight of the 16 Canadian schools (50%). Response rates for the respondent subgroups ranged from 27% for the deans to 57% for the clinical chairs. Overall, the most frequently mentioned problems concerned the evaluation of teaching. General complaints about the inadequacy of current methods to evaluate teaching performance were most common--more than one in four respondents raised this issue--but the respondents also had specific complaints about student evaluations of teaching and the insufficient recognition given to teaching in the academic reward system. The frequencies with which other concerns were expressed tended to be related to the respondents' roles. These problems included concerns about the methods and measures used to assess research and scholarship and the quality of clinical care, the nonuniformity of evaluation processes and criteria for promotion among departments, the absence of regular evaluations, and the failure to link the results of evaluation to salary.

CONCLUSIONS

The study population was not random; indeed, it was probably biased toward those who felt strongly (and perhaps negatively) about the current evaluation system. Still, the intensity with which views were expressed was striking. Improving the evaluation of faculty teaching undoubtedly remains one of medical education's greatest challenges.

BACKGROUND

Many biomedical publications refer to data obtained from collections of biosamples. Sharing such bioresources (biological samples, data, and databases) is paramount for the present governance of research. Recognition of the effort involved in generating, maintaining, and sharing high quality bioresources is poorly organized, which does not encourage sharing. At publication level, the recognition of such resources is often neglected and/or highly heterogeneous. This is a true handicap for the traceability of bioresource use. The aim of this article is to propose, for the first time, a guideline for reporting bioresource use in research articles, named CoBRA: Citation of BioResources in journal Articles.

METHODS

As standards for citing bioresources are still lacking, the members of the journal editors subgroup of the Bioresource Research Impact Factor (BRIF) initiative developed a standardized and appropriate citation scheme for such resources by informing stakeholders about the subject and raising awareness among scientists and in science editors' networks, mapping this topic among other relevant initiatives, promoting actions addressed to stakeholders, launching surveys, and organizing focused workshops.

RESULTS

The European Association of Science Editors has adopted BRIF's suggestion to incorporate statements on biobanks in the Methods section of their guidelines. The BRIF subgroup agreed upon a proposed citation system: each individual bioresource that is used to perform a study and that is mentioned in the Methods section should be cited as an individual "reference [BIORESOURCE]" according to a delineated format. The EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network mentioned the proposed reporting guideline in their "guidelines under development" section.

CONCLUSIONS

Evaluating bioresources' use and impact requires that publications accurately cite such resources. Adopting the standard citation scheme described here will improve the quality of bioresource reporting and will allow their traceability in scientific publications, thus increasing the recognition of bioresources' value and relevance to research. Please see related article: http://dx.doi.org/10.1186/s12916-015-0284-9.

A time delay procedure was used to increase spontaneous verbalizations of 3 autistic children. Multiple baseline across behaviors designs were used with target responses, selected via a social validation procedure, of two spontaneous responses ("please" and "thank you") and one verbally prompted response ("you're welcome"). The results indicate gains across target behaviors for all children, with occurrence across other stimuli and settings. These gains were validated socially with 10 adults. Furthermore, increases in appropriate language had no effect on levels of inappropriate speech.

AUTHOR:e-mail address please Recently more men have reported a desire for larger, more muscular bodies. Muscle dysmorphia (MD) is a new syndrome in which individuals (usually men), although highly muscular, have a pathological belief that they are of very small musculature. As more men are motivated to take up training with weights in order to develop greater musculature, more cases of MD are likely to be encountered. A greater understanding and awareness of the syndrome are therefore needed. Therefore the aim of this study was to investigate perceptions of physical self in male weightlifters, one group with MD (n = 24) and one without (n = 30). Between group comparisons were made using the multidimensional body-self relations questionnaire. The findings confirm the nature of the disorder in that those with MD syndrome have poorer body image and are less happy with their bodies. Moreover, in addition to a desire for greater muscularity, they are very concerned not to gain fat. The results also suggest that future research into perceptions of specific body parts and health is warranted.

BACKGROUND

Gene regulatory networks serve as models from which to derive therapeutic intervention strategies, in particular, stationary control policies over time that shift the probability mass of the steady state distribution (SSD) away from states associated with undesirable phenotypes. Derivation of control policies is hindered by the high-dimensional state spaces associated with gene regulatory networks. Hence, network reduction is a fundamental issue for intervention.

RESULTS

The network model that has been most used for the study of intervention in gene regulatory networks is the probabilistic Boolean network (PBN), which is a collection of constituent Boolean networks (BNs) with perturbation. In this article, we propose an algorithm that reduces a BN with perturbation, designs a control policy on the reduced network and then induces that policy to the original network. The coefficient of determination (CoD) is used to choose a gene for deletion, and a reduction mapping is used to rewire the remaining genes. This CoD-reduction procedure is used to construct a reduced network, then either the previously proposed mean first-passage time (MFPT) or SSD stationary control policy is designed on the reduced network, and these policies are induced to the original network. The efficacy of the overall algorithm is demonstrated on networks of 10 genes or less, where it is possible to compare the steady state shifts of the induced and original policies (because the latter can be derived), and by applying it to a 17-gene gastrointestinal network where it is shown that there is substantial beneficial steady state shift.

BACKGROUND

The code for the algorithms is available at: http://gsp.tamu.edu/Publications/supplementary/ghaffari10a/ Please Contact Noushin Ghaffari at nghaffari@tamu.edu for further questions.

BACKGROUND

Supplementary data are available at Bioinformatics online.

BACKGROUND

Litigation documents reveal that pharmaceutical companies have paid physicians to promote off-label uses of their products through a number of different avenues. It is unknown whether physicians and scientists who have such conflicts of interest adequately disclose such relationships in the scientific publications they author.

RESULTS

We collected whistleblower complaints alleging illegal off-label marketing from the US Department of Justice and other publicly available sources (date range: 1996-2010). We identified physicians and scientists described in the complaints as having financial relationships with defendant manufacturers, then searched Medline for articles they authored in the subsequent three years. We assessed disclosures made in articles related to the off-label use in question, determined the frequency of adequate disclosure statements, and analyzed characteristics of the authors (specialty, author position) and articles (type, connection to off-label use, journal impact factor, citation count/year). We identified 39 conflicted individuals in whistleblower complaints. They published 404 articles related to the drugs at issue in the whistleblower complaints, only 62 (15%) of which contained an adequate disclosure statement. Most articles had no disclosure (43%) or did not mention the pharmaceutical company (40%). Adequate disclosure rates varied significantly by article type, with commentaries less likely to have adequate disclosure compared to articles reporting original studies or trials (adjusted odds ratio [OR] = 0.10, 95%CI = 0.02-0.67, p = 0.02). Over half of the authors (22/39, 56%) made no adequate disclosures in their articles. However, four of six authors with ≥ 25 articles disclosed in about one-third of articles (range: 10/36-8/25 [28%-32%]).

CONCLUSIONS

One in seven authors identified in whistleblower complaints as involved in off-label marketing activities adequately disclosed their conflict of interest in subsequent journal publications. This is a much lower rate of adequate disclosure than has been identified in previous studies. The non-disclosure patterns suggest shortcomings with authors and the rigor of journal practices. Please see later in the article for the Editors' Summary.

BACKGROUND

The use of antiemetics for children with vomiting is one of the most controversial decisions in the treatment of gastroenteritis in developed countries. Ondansetron, a selective serotonin receptor antagonist, has been found to be effective in improving the success of oral rehydration therapy. However, North American and European clinical practice guidelines continue to recommend against its use, stating that evidence of cost savings would be required to support ondansetron administration. Thus, an economic analysis of the emergency department administration of ondansetron was conducted. The primary objective was to conduct a cost analysis of the routine administration of ondansetron in both the United States and Canada.

RESULTS

A cost analysis evaluated oral ondansetron administration to children presenting to emergency departments with vomiting and dehydration secondary to gastroenteritis from a societal and health care payer's perspective in both the US and Canada. A decision tree was developed that incorporated the frequency of vomiting, intravenous insertion, hospitalization, and emergency department revisits. Estimates of the monetary costs associated with ondansetron use, intravenous rehydration, and hospitalization were derived from administrative databases or emergency department use. The economic burden in children administered ondansetron plus oral rehydration therapy was compared to those not administered ondansetron employing deterministic and probabilistic simulations. We estimated the costs or savings to society and health care payers associated with the routine administration of ondansetron. Sensitivity analyses considered variations in costs, treatment effects, and exchange rates. In the US the administration of ondansetron to eligible children would prevent approximately 29,246 intravenous insertions and 7,220 hospitalizations annually. At the current average wholesale price, its routine administration to eligible children would annually save society US$65.6 million (US$49.1-US$81.1) and health care payers US$61.1 million (US$46.2-US$76.3). In Canada the administration of ondansetron to eligible children would prevent 4,065 intravenous insertions and 1,003 hospitalizations annually. Its routine administration would annually save society CDN$1.72 million (CDN$1.15-CDN$1.89) and the health care system CDN$1.18 million (CDN$0.88-CDN$1.41).

CONCLUSIONS

In countries where intravenous rehydration is often employed, the emergency department administration of oral ondansetron to children with dehydration and vomiting secondary to gastroenteritis results in significant monetary savings compared to a no-ondansetron policy. Please see later in the article for the Editors' Summary.

Palatogenesis, the formation of the palate, is a dynamic process regulated by a complex series of context-dependent morphogenetic signaling events. Many genes involved in palatogenesis have been discovered through the use of genetically manipulated mouse models as well as from human genetic studies, but the roles of these genes and their products in signaling networks regulating palatogenesis are still poorly known. In this review, we give a brief overview on palatogenesis and introduce key signaling cascades leading to formation of the intact palate. Moreover, we review conceptual differences between pathway biology and network biology and discuss how some of the recent technological advances in conjunction with mouse genetic models have contributed to our understanding of signaling networks regulating palate growth and fusion. For further resources related to this article, please visit the WIREs website.

BACKGROUND

The authors have declared no conflicts of interest for this article.