The effects of variability on context effects and psychometric function slopes in speaking rate normalizationa).

Acoustic context influences speech perception, but contextual variability restricts this influence. Assgari and Stilp [J. Acoust. Soc. Am. 138, 3023-3032 (2015)] demonstrated that when categorizing vowels, variability in who spoke the preceding context sentence on each trial but not the sentence contents diminished the resulting spectral contrast effects (perceptual shifts in categorization stemming from spectral differences between sounds). Yet, how such contextual variability affects temporal contrast effects (TCEs) (also known as speaking rate normalization; categorization shifts stemming from temporal differences) is unknown. Here, stimuli were the same context sentences and conditions (one talker saying one sentence, one talker saying 200 sentences, 200 talkers saying 200 sentences) used in Assgari and Stilp [J. Acoust. Soc. Am. 138, 3023-3032 (2015)], but set to fast or slow speaking rates to encourage perception of target words as "tier" or "deer," respectively. In Experiment 1, sentence variability and talker variability each diminished TCE magnitudes; talker variability also produced shallower psychometric function slopes. In Experiment 2, when speaking rates were matched across the 200-sentences conditions, neither TCE magnitudes nor slopes differed across conditions. In Experiment 3, matching slow and fast rates across all conditions failed to produce equal TCEs and slopes everywhere. Results suggest a complex interplay between acoustic, talker, and sentence variability in shaping TCEs in speech perception.

Musical training is not associated with spectral context effects in instrument sound categorization.

Musicians display a variety of auditory perceptual benefits relative to people with little or no musical training; these benefits are collectively referred to as the "musician advantage." Importantly, musicians consistently outperform nonmusicians for tasks relating to pitch, but there are mixed reports as to musicians outperforming nonmusicians for timbre-related tasks. Due to their experience manipulating the timbre of their instrument or voice in performance, we hypothesized that musicians would be more sensitive to acoustic context effects stemming from the spectral changes in timbre across a musical context passage (played by a string quintet then filtered) and a target instrument sound (French horn or tenor saxophone; Experiment 1). Additionally, we investigated the role of a musician's primary instrument of instruction by recruiting French horn and tenor saxophone players to also complete this task (Experiment 2). Consistent with the musician advantage literature, musicians exhibited superior pitch discrimination to nonmusicians. Contrary to our main hypothesis, there was no difference between musicians and nonmusicians in how spectral context effects shaped instrument sound categorization. Thus, musicians may only outperform nonmusicians for some auditory skills relevant to music (e.g., pitch perception) but not others (e.g., timbre perception via spectral differences).

Talker adaptation or "talker" adaptation? Musical instrument variability impedes pitch perception.

Listeners show perceptual benefits (faster and/or more accurate responses) when perceiving speech spoken by a single talker versus multiple talkers, known as talker adaptation. While near-exclusively studied in speech and with talkers, some aspects of talker adaptation might reflect domain-general processes. Music, like speech, is a sound class replete with acoustic variation, such as a multitude of pitch and instrument possibilities. Thus, it was hypothesized that perceptual benefits from structure in the acoustic signal (i.e., hearing the same sound source on every trial) are not specific to speech but rather a general auditory response. Forty nonmusician participants completed a simple musical task that mirrored talker adaptation paradigms. Low- or high-pitched notes were presented in single- and mixed-instrument blocks. Reflecting both music research on pitch and timbre interdependence and mirroring traditional "talker" adaptation paradigms, listeners were faster to make their pitch judgments when presented with a single instrument timbre relative to when the timbre was selected from one of four instruments from trial to trial. A second experiment ruled out the possibility that participants were responding faster to the specific instrument chosen as the single-instrument timbre. Consistent with general theoretical approaches to perception, perceptual benefits from signal structure are not limited to speech.

Clear speech promotes speaking rate normalization.

When speaking in noisy conditions or to a hearing-impaired listener, talkers often use clear speech, which is typically slower than conversational speech. In other research, changes in speaking rate affect speech perception through speaking rate normalization: Slower context sounds encourage perception of subsequent sounds as faster, and vice versa. Here, on each trial, listeners heard a context sentence before the target word (which varied from "deer" to "tier"). Clear and slowed conversational context sentences elicited more "deer" responses than conversational sentences, consistent with rate normalization. Changing speaking styles aids speech intelligibility but might also produce other outcomes that alter sound/word recognition.

Clearly, fame isn't everything: Talker familiarity does not augment talker adaptation.

Familiarity with a talker's voice provides numerous benefits to speech perception, including faster responses and improved intelligibility in quiet and in noise. Yet, it is unclear whether familiarity facilitates talker adaptation, or the processing benefit stemming from hearing speech from one talker compared to multiple different talkers. Here, listeners completed a speeded recognition task for words presented in either single-talker or multiple-talker blocks. Talkers were either famous (the last five Presidents of the United States of America) or non-famous (other male politicians of similar ages). Participants either received no information about the talkers before the word recognition task (Experiments 1 and 3) or heard the talkers and saw their names first (Experiment 2). As expected, responses were faster in the single-talker blocks than in the multiple-talker blocks. Famous voices elicited faster responses in Experiment 1, but familiarity effects were extinguished in Experiment 2, possibly by hearing all voices recently before the experiment. When talkers were counterbalanced across single-talker and mixed-talker blocks in Experiment 3, no familiarity effects were observed. Predictions of familiarity facilitating talker adaptation (smaller increase in response times across single- and multiple-talker blocks for famous voices) were not confirmed. Thus, talker familiarity might not augment adaptation to a consistent talker.

Nonspeech sounds are not all equally good at being nonspeech.

Perception of speech sounds has a long history of being compared to perception of nonspeech sounds, with rich and enduring debates regarding how closely they share similar underlying processes. In many instances, perception of nonspeech sounds is directly compared to that of speech sounds without a clear explanation of how related these sounds are to the speech they are selected to mirror (or not mirror). While the extreme acoustic variability of speech sounds is well documented, this variability is bounded by the common source of a human vocal tract. Nonspeech sounds do not share a common source, and as such, exhibit even greater acoustic variability than that observed for speech. This increased variability raises important questions about how well perception of a given nonspeech sound might resemble or model perception of speech sounds. Here, we offer a brief review of extremely diverse nonspeech stimuli that have been used in the efforts to better understand perception of speech sounds. The review is organized according to increasing spectrotemporal complexity: random noise, pure tones, multitone complexes, environmental sounds, music, speech excerpts that are not recognized as speech, and sinewave speech. Considerations are offered for stimulus selection in nonspeech perception experiments moving forward.

Peyronie disease: a clinicopathologic study of 71 cases with emphasis on histopathologic patterns and prevalent metaplastic ossification.

Peyronie disease (PD) is a benign, superficial fibromatosis involving the fascial structures of the penis, causing deformity, pain, and loss of function, for which there are few contemporary studies of the histopathology. We performed a multi-institutional review of 74 routine and consultation specimens submitted with clinical concern for PD. Of these, three non-PD lesions were identified and excluded (a myointimoma, a mammary-type myofibroblastoma, and fibrocalcific atherosclerosis). Of the 71 confirmed to be PD, the majority of patients were white (83%), with a median age of 55 years (range: 26-88). The dorsal aspect of the penis was the most common site involved (78%), followed by lateral (12%) and ventral (10%) aspects. The median degree of curvature was 70° (range: 20-360°). On review, three overall histologic patterns characterized the lesions resected: dense fibrotic plaque (61%), dense fibrotic plaque with focal or patchy metaplastic ossification (35%), and plaque composed predominantly of metaplastic ossification (4%). The fibrotic component was predominantly nodular (18%), hyalinized/lamellar (46%), or mixed (32%), excepting two cases consisting entirely of metaplastic bone. Chronic inflammation, when present, was most often focal and perivascular in distribution. In one case, an excision after collagenase treatment showed myxoid change and increased stromal cellularity. Overall, these findings define the range of PD histology, particularly emphasizing that the calcification noted clinically nearly always represents bona fide metaplastic ossification. Such context will be of value in evaluating specimens prospectively, in light of changing practices and the use of new technologies for treatment.

Pyoderma gangrenosum developing after chest tube placement in a patient with chronic lymphocytic leukemia.

Diagnosis of a neutrophilic dermatosis, such as pyoderma gangrenosum (PG), often is challenging at onset because it can be impossible to distinguish clinically and histopathologically from an acute infection in an immunosuppressed patient, necessitating a detailed patient history as well as correlation pathology with microbial tissue cultures. The dermatologist's ability to distinguish a neutrophilic dermatosis from active infection is of paramount importance, as the decision to treat with surgical debridement, in addition to an antibiotic regimen, can have grave consequences in the misdiagnosed patient. We present a case of PG occurring at a chest tube site in a patient with chronic lymphocytic leukemia (CLL) and highlight the challenges and therapeutic importance of arriving at the correct diagnosis.

A geometric approach for computing tolerance bounds for elastic functional data.

We develop a method for constructing tolerance bounds for functional data with random warping variability. In particular, we define a generative, probabilistic model for the amplitude and phase components of such observations, which parsimoniously characterizes variability in the baseline data. Based on the proposed model, we define two different types of tolerance bounds that are able to measure both types of variability, and as a result, identify when the data has gone beyond the bounds of amplitude and/or phase. The first functional tolerance bounds are computed via a bootstrap procedure on the geometric space of amplitude and phase functions. The second functional tolerance bounds utilize functional Principal Component Analysis to construct a tolerance factor. This work is motivated by two main applications: process control and disease monitoring. The problem of statistical analysis and modeling of functional data in process control is important in determining when a production has moved beyond a baseline. Similarly, in biomedical applications, doctors use long, approximately periodic signals (such as the electrocardiogram) to diagnose and monitor diseases. In this context, it is desirable to identify abnormalities in these signals. We additionally consider a simulated example to assess our approach and compare it to two existing methods.

Biologics and biosimilars.

Biological drugs are large, complex glycoprotein molecules produced in living organisms. Revolutionary treatments for many conditions, biologics used in dermatology will face patent expiration, opening opportunities for competitive versions. Biologic drugs are so complex such that it is impossible to reproduce them exactly. Biosimilars are designed to be highly similar, though not identical, to the innovator product. Because biosimilars are not exact replicates of innovator biologics, guidelines have suggested that biosimilars should be considered as unique therapeutic interventions, requiring unique names and physician notification prior to substitution. However, because biologics can never be replicated exactly, even innovator biologics have inherent batch-to-batch variability; when the second batch of innovator products were released, physicians began prescribing non-identical variants of biologics to their patients, accepting the possibility of variation in clinical effects. Unlike the variants in innovator products, biosimilars will provide clinical trial data demonstrating similar clinical effects, though there will always be some degree of uncertainty in how much clinical impact will be result from the variation in both innovator and biosimilar products. How biosimilars are approved and how we use biosimilars will need to balance considerations of cost and development time with the possibility of variation in biological response.

A cluster of three cases of leptospirosis in dairy farm workers in New Zealand.

AIMS: We report a cluster of three cases of leptospirosis on a New Zealand dairy farm, with regard to clinical, laboratory, and environmental findings. The cluster is discussed against the annual incidence of leptospirosis in humans and cattle, and the vaccination of cattle as one means of preventing human cases on farms. METHDOS: The three cases were investigated by case interview and review of clinical and laboratory information. A site visit was made to the farm to assess environmental risk. Relevant veterinary information relating to the cattle herds was reviewed. RESULTS: Most of the symptoms exhibited by the three patients were consistent with primary phase leptospirosis. Different methods of laboratory diagnosis were used with each case. However, two cases were confirmed as leptospirosis and in both the causative agent was Leptospira borgpetersenii serovar (sv) Hardjo. The third case had a milder illness, received doxycycline early, and was regarded as a 'probable' case as there were no confirmatory diagnostic results. All three cases had worked on the same dairy farm during their incubation period, where the highest risk environment was the milking shed and potential exposure to urine splashes from infected cattle. Also there were inadequacies in the herd vaccination programme. CONCLUSIONS: There are options for minimising risk to dairy farm workers in New Zealand. No human vaccine exists in this country. Leptospira borgpetersenii serovar (sv) Hardjo (serovar Hardjo) is endemic in New Zealand dairy cattle without causing apparent disease. L. Pomona is a sporadic infection but can cause abortions. A cattle vaccine against these serovars was introduced in New Zealand in 1979, after which there was a general fall in notifications of human cases of leptospirosis. This was attributed to the overall decrease in these two serovars among the livestock population. Vaccination of farm livestock for leptospirosis is an integral factor in preventing human cases. We note the New Zealand initiative to combine vaccination with a risk management programme operated by veterinarians, called Leptosure, to reduce the risk of human leptospirosis on dairy farms. The efficacy of using doxycycline as a prophylaxis for preventing human infection in trials is reviewed. Other preventative strategies include the use of personal protective equipment to cover the mouth and nose, eyes and all skin breaks, farm workers and rural clinicians being aware of the signs and symptoms of leptospirosis, and prompt treatment of cases with antibiotics.

Moderate GLUT4 overexpression improves insulin sensitivity and fasting triglyceridemia in high-fat diet-fed transgenic mice.

The GLUT4 facilitative glucose transporter mediates insulin-dependent glucose uptake. We tested the hypothesis that moderate overexpression of human GLUT4 in mice, under the regulation of the human GLUT4 promoter, can prevent the hyperinsulinemia that results from obesity. Transgenic mice engineered to express the human GLUT4 gene and promoter (hGLUT4 TG) and their nontransgenic counterparts (NT) were fed either a control diet (CD) or a high-fat diet (HFD) for up to 10 weeks. Homeostasis model assessment of insulin resistance scores revealed that hGLUT4 TG mice fed an HFD remained highly insulin sensitive. The presence of the GLUT4 transgene did not completely prevent the metabolic adaptations to HFD. For example, HFD resulted in loss of dynamic regulation of the expression of several metabolic genes in the livers of fasted and refed NT and hGLUT4 TG mice. The hGLUT4 TG mice fed a CD showed no feeding-dependent regulation of SREBP-1c and fatty acid synthase (FAS) mRNA expression in the transition from the fasted to the fed state. Similarly, HFD altered the response of SREBP-1c and FAS mRNA expression to feeding in both strains. These changes in hepatic gene expression were accompanied by increased nuclear phospho-CREB in refed mice. Taken together, a moderate increase in expression of GLUT4 is a good target for treatment of insulin resistance.

Detection of tetrodotoxin from the grey side-gilled sea slug - Pleurobranchaea maculata, and associated dog neurotoxicosis on beaches adjacent to the Hauraki Gulf, Auckland, New Zealand.

Investigations into a series of dog poisonings on beaches in Auckland, North Island, New Zealand, resulted in the identification of tetrodotoxin (TTX) in the grey side-gilled sea slug, Pleurobranchaea maculata. The levels of TTX in P. maculata, assayed by liquid chromatography-mass spectrometry (LC-MS) ranged from 91 to 850 mg kg(-1) with a median level of 365 mg kg(-1) (n = 12). In two of the dog poisoning cases, vomit and gastrointestinal contents were found to contain TTX. Adult P. maculata were maintained in aquaria for several weeks. Levels of TTX decreased only slightly with time. While in the aquaria, P. maculata spawned, with each individual producing 2-4 egg masses. The egg masses and 2-week old larvae also contained TTX. Tests for other marine toxins were negative and no other organisms from the area contained TTX. This is the first time TTX has been identified in New Zealand and the first detection of TTX in an opisthobranch.

Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy.

Acute gastroenteritis remains a common illness among infants and children throughout the world. Among children in the United States, acute diarrhea accounts for >1.5 million outpatient visits, 200,000 hospitalizations, and approximately 300 deaths/year. In developing countries, diarrhea is a common cause of mortality among children aged <5 years, with an estimated 2 million deaths annually. Oral rehydration therapy (ORT) includes rehydration and maintenance fluids with oral rehydration solutions (ORS), combined with continued age-appropriate nutrition. Although ORT has been instrumental in improving health outcomes among children in developing countries, its use has lagged behind in the United States. This report provides a review of the historical background and physiologic basis for using ORT and provides recommendations for assessing and managing children with acute diarrhea, including those who have become dehydrated. Recent developments in the science of gastroenteritis management have substantially altered case management. Physicians now recognize that zinc supplementation can reduce the incidence and severity of diarrheal disease, and an ORS of reduced osmolarity (i.e., proportionally reduced concentrations of sodium and glucose) has been developed for global use. The combination of oral rehydration and early nutritional support has proven effective throughout the world in treating acute diarrhea. In 1992, CDC prepared the first national guidelines for managing childhood diarrhea (CDC. The management of acute diarrhea in children: oral rehydration, maintenance, and nutritional therapy. MMWR 1992;41[No. RR-16]), and this report updates those recommendations. This report reviews the historical background and scientific basis of ORT and provides a framework for assessing and treating infants and children who have acute diarrhea. The discussion focuses on common clinical scenarios and traditional practices, especially regarding continued feeding. Limitations of ORT, ongoing research in the areas of micronutrient supplements, and functional foods are reviewed as well. These updated recommendations were developed by specialists in managing gastroenteritis, in consultation with CDC and external consultants. Relevant literature was identified through an extensive MEDLINE search by using related terms. Articles were then reviewed for their relevance to pediatric practice, with emphasis on U.S. populations. Unpublished references were sought from the external consultants and other researchers. In the United States, adoption of these updated recommendations could substantially reduce medical costs and childhood hospitalizations and deaths caused by diarrhea.