Silver Ions Inhibit Bacterial Movement and Stall Flagellar Motor.

Silver (Ag) in different forms has been gaining broad attention due to its antimicrobial activities and the increasing resistance of bacteria to commonly prescribed antibiotics. However, various aspects of the antimicrobial mechanism of Ag have not been understood, including how Ag affects bacterial motility, a factor intimately related to bacterial virulence. Here, we report our study on how Ag+ ions affect the motility of E. coli bacteria using swimming, tethering, and rotation assays. We observed that the bacteria slowed down dramatically by >70% when subjected to Ag+ ions, providing direct evidence that Ag+ ions inhibit the motility of bacteria. In addition, through tethering and rotation assays, we monitored the rotation of flagellar motors and observed that the tumbling/pausing frequency of bacteria increased significantly by 77% in the presence of Ag+ ions. Furthermore, we analyzed the results from the tethering assay using the hidden Markov model (HMM) and found that Ag+ ions decreased bacterial tumbling/pausing-to-running transition rate significantly by 75%. The results suggest that the rotation of bacterial flagellar motors was stalled by Ag+ ions. This work provided a new quantitative understanding of the mechanism of Ag-based antimicrobial agents in bacterial motility.

The Surprising Ease of Finding Optimal Solutions for Controlling Nonlinear Phenomena in Quantum and Classical Complex Systems.

This Perspective addresses the often observed surprising ease of achieving optimal control of nonlinear phenomena in quantum and classical complex systems. The circumstances involved are wide-ranging, with scenarios including manipulation of atomic scale processes, maximization of chemical and material properties or synthesis yields, Nature's optimization of species' populations by natural selection, and directed evolution. Natural evolution will mainly be discussed in terms of laboratory experiments with microorganisms, and the field is also distinct from the other domains where a scientist specifies the goal(s) and oversees the control process. We use the word "control" in reference to all of the available variables, regardless of the circumstance. The empirical observations on the ease of achieving at least good, if not excellent, control in diverse domains of science raise the question of why this occurs despite the generally inherent complexity of the systems in each scenario. The key to addressing the question lies in examining the associated control landscape, which is defined as the optimization objective as a function of the control variables that can be as diverse as the phenomena under consideration. Controls may range from laser pulses, chemical reagents, chemical processing conditions, out to nucleic acids in the genome and more. This Perspective presents a conjecture, based on present findings, that the systematics of readily finding good outcomes from controlled phenomena may be unified through consideration of control landscapes with the same common set of three underlying assumptions─the existence of an optimal solution, the ability for local movement on the landscape, and the availability of sufficient control resources─whose validity needs assessment in each scenario. In practice, many cases permit using myopic gradient-like algorithms while other circumstances utilize algorithms having some elements of stochasticity or introduced noise, depending on whether the landscape is locally smooth or rough. The overarching observation is that only relatively short searches are required despite the common high dimensionality of the available controls in typical scenarios.

Planetary health and sustainability teaching in UK medical education: A review of medical school curricula.

BACKGROUND: The doctors of the future need to be empowered to deliver healthcare sustainably while protecting their patients' health in the context of a degrading environment. This study aimed to objectively review the extent and nature of the teaching of planetary health and sustainability topics in UK medical education. METHODS: A multi-centre national review of the timetabled teaching sessions in medical courses in the UK during the academic year 2020/2021 against the General Medical Council's adopted 'Educating for Sustainable Healthcare - Priority Learning Outcomes'. Medical students were recruited and reviewed the entirety of their own institution's online teaching materials associated with core teaching sessions using a standardised data collection tool. Learning outcome coverage and estimated teaching time were calculated and used to rank participating medical schools. RESULTS: 45% of eligible UK medical schools were included in the study. The extent of teaching varied considerably amongst courses. Mean coverage of the 13 learning outcomes was 9.9 (SD:2.5) with a mean estimated teaching time of 140 min (SD:139). Courses with dedicated planetary health and sustainability sessions ranked best. CONCLUSION: There is large disparity in the education that medical students receive on these topics. Teaching may not adequately prioritise sustainability or reflect advances in planetary health knowledge.[Box: see text].

Seniority of the assistant surgeon and perioperative outcomes in robotic-assisted proctectomy for rectal cancer.

The background of this study is to evaluate the impact of the assistant surgeon's in robotic-assisted proctectomy (RAP) on perioperative outcomes. A retrospective analysis of all patients who underwent RAP for rectal adenocarcinoma between 2011 and 2020 was conducted. Patient cohort was divided into three groups based on the assistant surgeon's training level: post-graduate years (PGY) 1-3 surgical residents (Group 1), PGY 4-5 surgical residents (Group 2), and board-certified general surgeons (Group 3). Overall, 175 patients were included in the study: 29 patients (17%) in Group 1, 84 (48%) in Group 2, and 62 (35%) in Group 3. The median tumor distance from the anal verge was 8 cm in all groups (p = 0.73). The median operative time was similar across all groups: 290, 291, and 281 min in Groups 1, 2, and 3, respectively (p = 0.69). In a multivariable analysis, the lack of association between assistant training level and procedure time maintained when adjusting for the year of operation (p = 0.84). Patients operated with junior residents as assistant surgeons (Group 1) had a more postoperative complications (p = 0.01) and a slightly longer hospital length of stay [7 days, interquartile range (IQR) 3], compared to those operated by assistant surgeons that were senior residents or attendings (6 IQR 2.5, and 6 IQR 2 in Groups 2 and 3, respectively; p = 0.02). Conversion rates (p = 0.12), intraoperative complications (p = 0.39), major postoperative complications (Clavien-Dindo ≥ 3; p = 0.32), 30-day readmission (p = 0.45), and mortality (p = 0.99) were similar between the groups. Robotic-assisted proctectomy performed with the assistance of a junior resident was found to be correlated with worse postoperative outcomes compared to more experienced assistants. No difference was seen in intraoperative outcomes.

Naples Prognostic Score to Predict Postoperative Complications After Colectomy for Diverticulitis.

BACKGROUND: The Naples Prognostic Score (NPS) has proven efficacy as a prognostic tool for postoperative outcomes in patients undergoing surgery for neoplastic diseases. However, the role of the NPS score in inflammatory surgical diseases has not yet been studied. We aimed to evaluate NPS predictive value in patients undergoing colectomy due to diverticulitis. METHODS: A single-center retrospective study including all patients who underwent colectomy for diverticulitis between July 2008 and March 2020 was established. Patients' demographics, clinical and surgical data were recorded and analyzed. Patients were scored on a scale of 0-4 and received one point for preoperation albumin <4 g/dL, cholesterol ≤180 mg/dL, Neutrophil to Lymphocyte Ratio >2.96, and Lymphocyte to Monocyte ≤4.44. RESULTS: Out of 3292 patients admitted because of diverticulitis during the study period, 159 patients (4.83%) underwent colectomy. Of those patients, fifty patients were eligible for NPS analysis. 35 patients (70%) were females with a mean age of 62.81 ± 14.51. Thirty-two (64%) patients underwent an elective operation. The postoperative complications rate was 36% (N = 18). The mortality rate was 6% (N = 3). ROC showed a strong association between the NPS and mortality (area = .88, P = .03) and wound infection (area = .78, P = .01). In patients who underwent urgent surgery, there was an association between NPS and re-operation (P = .04). There was a correlation between NPS and Clavien-Dindo score (Spearman's coefficient = .284, P = .045). CONCLUSIONS/DISCUSSION: The Naples prognostic score is an effective tool for predicting postoperative complications in patients undergoing colectomy for diverticulitis. It may assist the surgeon in deciding on extent of the operation for diverticulitis and in elective cases also on timing.

[UPPER GASTROINTESTINAL BLEEDING CAUSED BY BREAST ANGIOSARCOMA METASTASIS LOCATED IN THE GASTRO-ESOPHAGEAL JUNCTION].

INTRODUCTION: Angiosarcomas are rare and aggressive tumors that originate from endothelial cells and make up roughly 2-3% of all soft-tissue sarcomas. Breast angiosarcomas may be idiopathic or secondary to radiation therapy or chronic lymphatic edema. Primary angiosarcoma of the gastrointestinal (GI) tract is rare and usually causes abdominal pain or GI bleeding. In this case report, we present a patient who appeared with upper gastrointestinal bleeding due to a radiation-induced breast angiosarcoma metastatic lesion in the gastroesophageal junction (GEJ). To the best of our knowledge, breast angiosarcoma metastases to the GEJ were not previously described, and moreover, GI bleeding secondary to breast angiosarcoma GI metastases was not previously reported.

Mid-infrared spectral reconstruction with dielectric metasurfaces and dictionary learning.

Mid-infrared (MIR) spectroscopy has numerous industrial applications and is usually performed with Fourier-transform infrared (FTIR) spectrometers. While these work well for many purposes, there is currently much interest in alternative approaches that are smaller and lighter, i.e., MIR microspectrometers. Here we investigate all-dielectric metasurfaces as spectral filters for MIR microspectrometers. Two metasurface types are studied. For the first, we design, fabricate, and test a metasurface with a narrow and angularly tunable transmission stop band. We use it to reconstruct the transmission spectra of various materials. The second metasurface, investigated theoretically, possesses narrow passband features via symmetry-protected bound states in the continuum.

Thrombocytosis Predicts Surgical Site Infection in Head and Neck Microvascular Surgery- A Pilot Study.

OBJECTIVE/HYPOTHESIS: Early and objective prediction of complications in head and neck reconstructive surgery could decrease morbidity and prolonged hospital stays but unfortunately most complications are not identified until their effect is fully realized. There are limited data regarding the association of platelet levels and post-operative complications. Post-operative thrombocytosis (POTCT) is proposed as a possible indicator for complications following free-flap reconstruction. STUDY DESIGN: Retrospective review. METHODS: A multisite retrospective chart review of patients undergoing free tissue transfer between 2013 and 2018 was undertaken. POTCT was recorded and data normalized between institutions. Data were compared between groups using t-tests and logistic regression (P < .05). A lag-1 difference was used to compare the rate of change in platelet values. RESULTS: A total of 398 patients were included. POTCT and a rate of change of 30 K between POD5 and POD6 was significantly associated with the presence of post-operative complication (P = .007). Additionally, lag-1 difference demonstrated a significant association of change in daily platelet counts and complication rates. CONCLUSIONS: Isolated POTCT may be an early predictor of complications in HNC patients undergoing free-flap reconstruction. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1542-1547, 2021.

Sensing Water Absorption in Hygrothermally Aged Epoxies with Terahertz Time-Domain Spectroscopy.

In the field of non-destructive testing, terahertz sensing has been used to analyze a wide range of materials where the most successful applications have involved materials that are semi-transparent to terahertz radiation. In this work, we demonstrate the sensitivity of terahertz time-domain spectroscopy to quantify water absorption in hygrothermally aged simple and commercial epoxy systems supported by conventional gravimetric analysis.

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease.

The cluster of differentiation 40 (CD40) is activated by the CD40 ligand (CD40L) in a variety of diverse cells types and regulates important processes associated with kidney disease. The CD40/CD40L signaling cascade has been comprehensively studied for its roles in immune functions, whereas the signaling axis involved in local kidney injury has only drawn attention in recent years. Clinical studies have revealed that circulating levels of soluble CD40L (sCD40L) are associated with renal function in the setting of kidney disease. Levels of the circulating CD40 receptor (sCD40), sCD40L, and local CD40 expression are tightly related to renal injury in different types of kidney disease. Additionally, various kidney cell types have been identified as non-professional antigen-presenting cells (APCs) that express CD40 on the cell membrane, which contributes to the interactions between immune cells and local kidney cells during the development of kidney injury. Although the potential for adverse CD40 signaling in kidney cells has been reported in several studies, a summary of those studies focusing on the role of CD40 signaling in the development of kidney disease is lacking. In this review, we describe the outcomes of recent studies and summarize the potential therapeutic methods for kidney disease which target CD40.

Fiber reorientation in hybrid helicoidal composites.

Naturally occurring biological materials with stiff fibers embedded in a ductile matrix are commonly known to achieve excellent balance between stiffness, strength and ductility. In particular, biological composite materials with helicoidal architecture have been shown to exhibit enhanced damage tolerance and increased impact energy absorption. However, the role of fiber reorientation inside the flexible matrix of helicoid composites on their mechanical behaviors have not yet been extensively investigated. In the present work, we introduce a Discontinuous Fiber Helicoid (DFH) composite inspired by both the helicoid microstructure in the cuticle of mantis shrimp and the nacreous architecture of the red abalone shell. We employ 3D printed specimens, analytical models and finite element models to analyze and quantify in-plane fiber reorientation in helicoid architectures with different geometrical features. We also introduce additional architectures, i.e., single unidirectional lamina and mono-balanced architectures, for comparison purposes. Compared with associated mono-balanced architectures, helicoid architectures exhibit less fiber reorientation values and lower values of strain stiffening. The explanation for this difference is addressed in terms of the measured in-plane deformation, due to uniaxial tensile of the laminae, correlated to lamina misorientation with respect to the loading direction and lay-up sequence.

Targeting of CD38 by the Tumor Suppressor miR-26a Serves as a Novel Potential Therapeutic Agent in Multiple Myeloma.

Multiple myeloma is an incurable refractory hematologic malignancy arising from plasma cells in the bone marrow. Here we investigated miR-26a function in multiple myeloma and tested single-wall carbon nanotube delivery of miR-26a in vitro and in vivo. miR-26a was downregulated in patients with multiple myeloma cells compared with plasma cells from healthy donors. miR-26a overexpression inhibited proliferation and migration and induced apoptosis in multiple myeloma cell lines. To identify the targets of miR-26a, RPMI8226-V-miR-26-GFP and RPMI8226-V-GFP cells were cultured using stable isotope labeling by amino acids in cell culture (SILAC) medium, followed by mass spectrometry analysis. In multiple myeloma cells overexpressing miR-26a, CD38 protein was downregulated and subsequently confirmed to be a direct target of miR-26a. Depletion of CD38 in multiple myeloma cells duplicated the multiple myeloma inhibition observed with exogenous expression of miR-26a, whereas restoration of CD38 overcame the inhibition of miR-26a in multiple myeloma cells. In a human multiple myeloma xenograft mouse model, overexpression of miR-26a inhibited CD38 expression, provoked cell apoptosis, and inhibited cell proliferation. Daratumumab is the first CD38 antibody drug for monotherapy and combination therapy for patients with multiple myeloma, but eventually resistance develops. In multiple myeloma cells, CD38 remained at low level during daratumumab treatment, but a high-quality response is sustained. In daratumumab-resistant multiple myeloma cells, CD38 expression was completely restored but failed to correlate with daratumumab-induced cell death. Therefore, a therapeutic strategy to confer selection pressure to maintain low CD38 expression in multiple myeloma cells may have clinical benefit. SIGNIFICANCE: These results highlight the tumor suppressor function of miR-26a via its targeting of CD38 and suggest the therapeutic potential of miR-26a in patients with multiple myeloma.

A new approach to OSCE preparation - PrOSCEs.

BACKGROUND: Objectively structured clinical examinations (OSCEs) are a stressful experience for many health care students and professionals in training. Mock OSCEs have been shown to be beneficial for student OSCE preparation. However, due to their expense and administrative burden students may only get a few opportunities to partake in these. To address this gap in student preparation a series of regularly run totally peer led multi-role practice OSCEs (PrOSCEs) was developed. METHODS: Fifteen PrOSCEs were run over five-months. A total of 32 second year medical students took part, all of whom were enrolled on the graduate-entry programme at the University of Southampton. In each PrOSCE, 18 participants rotated through the roles of 'student', 'examiner' and 'patient' in six simulated stations designed by their peers. Peer feedback was provided after each station. At the end of the series of PrOSCEs students were asked to fill in an anonymous online feedback survey to assess the usefulness of the PrOSCEs in exam preparation. RESULTS: Twenty-two students responded to the survey. 100% of respondents deemed routine participation either 'very useful' or 'useful' in preparing for their exam. PrOSCEs were found to improve confidence (mean = 7.9/10, 95% CI 7.4-8.3), expected performance (mean = 7.5/10, 95% CI 6.8-8.2) and help guide revision (mean = 8.3/10, 95% CI 7.6-9.0). Self-perceived teaching performance and confidence in providing feedback was also positively associated with participation. The most beneficial roles were 'student' and 'station creator'. Free-text feedback suggests that the informal setting and regular practice were particularly beneficial. CONCLUSION: The peer-led nature of the PrOSCEs allows for a low cost, low administrative burden and easy to replicate adjunct or alternative to large scale mock OSCEs. In addition the multi-role aspect of this approach could enhance exam preparation and may also improve aptitude as a clinical teacher. Further studies are required to understand if repeated practice has beneficial implications on OSCE performance.

Extracellular Vesicles from Neurosurgical Aspirates Identifies Chaperonin Containing TCP1 Subunit 6A as a Potential Glioblastoma Biomarker with Prognostic Significance.

Glioblastoma, WHO-grade IV glioma, carries a dismal prognosis owing to its infiltrative growth and limited treatment options. Glioblastoma-derived extracellular vesicles (EVs; 30-1000 nm membranous particles) influence the microenvironment to mediate tumor aggressiveness and carry oncogenic cargo across the blood-brain barrier into the circulation. As such, EVs are biomarker reservoirs with enormous potential for assessing glioblastoma tumors in situ. Neurosurgical aspirates are rich sources of EVs, isolated directly from glioma microenvironments. EV proteomes enriched from glioblastoma (n = 15) and glioma grade II-III (n = 7) aspirates are compared and 298 differentially-abundant proteins (p-value < 0.00496) are identified using quantitative LC-MS/MS. Along with previously reported glioblastoma-associated biomarkers, levels of all eight subunits of the key molecular chaperone, T-complex protein 1 Ring complex (TRiC), are higher in glioblastoma-EVs, including CCT2, CCT3, CCT5, CCT6A, CCT7, and TCP1 (p < 0.00496). Analogous increases in TRiC transcript levels and DNA copy numbers are detected in silico; CCT6A has the greatest induction of expression and amplification in glioblastoma and shows a negative association with survival (p = 0.006). CCT6A is co-localized with EGFR at 7p11.2, with a strong tendency for co-amplification (p < 0.001). Immunohistochemistry corroborates the CCT6A proteomics measurements and indicated a potential link between EGFR and CCT6A tissue expression. Putative EV-biomarkers described here should be further assessed in peripheral blood.

Common foundations of optimal control across the sciences: evidence of a free lunch.

A common goal in the sciences is optimization of an objective function by selecting control variables such that a desired outcome is achieved. This scenario can be expressed in terms of a control landscape of an objective considered as a function of the control variables. At the most basic level, it is known that the vast majority of quantum control landscapes possess no traps, whose presence would hinder reaching the objective. This paper reviews and extends the quantum control landscape assessment, presenting evidence that the same highly favourable landscape features exist in many other domains of science. The implications of this broader evidence are discussed. Specifically, control landscape examples from quantum mechanics, chemistry and evolutionary biology are presented. Despite the obvious differences, commonalities between these areas are highlighted within a unified mathematical framework. This mathematical framework is driven by the wide-ranging experimental evidence on the ease of finding optimal controls (in terms of the required algorithmic search effort beyond the laboratory set-up overhead). The full scope and implications of this observed common control behaviour pose an open question for assessment in further work.This article is part of the themed issue 'Horizons of cybernetical physics'.

Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia.

We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as compared with controls. Orexin maintains wakefulness/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (n = 7), air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of 7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles) (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin-positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin-positive neurons in the hypothalamus and fibre expression in the pons, and that IHH exposure does not prevent the nicotine-induced increase. Thus, although both nicotine and IHH are risk factors for SIDS, it appears they have opposing effects on OxA and OxB expression, with the IHH exposure closely mimicking what we recently found in SIDS.

Imaging through the pupal case of Drosophila melanogaster.

The longstanding use of Drosophila as a model for cell and developmental biology has yielded an array of tools. Together, these techniques have enabled analysis of cell and developmental biology from a variety of methodological angles. Live imaging is an emerging method for observing dynamic cell processes, such as cell division or cell motility. Having isolated mutations in uncharacterized putative cell cycle proteins it became essential to observe mitosis in situ using live imaging. Most live imaging studies in Drosophila have focused on the embryonic stages that are accessible to manipulation and observation because of their small size and optical clarity. However, in these stages the cell cycle is unusual in that it lacks one or both of the gap phases. By contrast, cells of the pupal wing of Drosophila have a typical cell cycle and undergo a period of rapid mitosis spanning about 20 hr of pupal development. It is easy to identify and isolate pupae of the appropriate stage to catch mitosis in situ. Mounting intact pupae provided the best combination of tractability and durability during imaging, allowing experiments to run for several hours with minimal impact on cell and animal viability. The method allows observation of features as small as, or smaller than, fly chromosomes. Adjustment of microscope settings and the details of mounting, allowed extension of the preparation to visualize membrane dynamics of adjacent cells and fluorescently labeled proteins such as tubulin. This method works for all tested fluorescent proteins and can capture submicron scale features over a variety of time scales. While limited to the outer 20 µm of the pupa with a conventional confocal microscope, this approach to observing protein and cellular dynamics in pupal tissues in vivo may be generally useful in the study of cell and developmental biology in these tissues.

Vowel identification by cochlear implant users: contributions of static and dynamic spectral cues.

Previous research has shown that normal hearing listeners can identify vowels in syllables on the basis of either quasi-static or dynamic spectral cues; however, it is not known how well cochlear implant (CI) users with current-generation devices can make use of these cues. The present study assessed vowel identification in adult CI users and a comparison group of young normal hearing (YNH) listeners. Stimuli were naturally spoken /dVd/ syllables and modified syllables that retained only quasi-static spectral cues from an 80-ms segment of the vowel center ("C80" stimuli) or dynamic spectral cues from two 20-ms segments of the vowel edges ("E20" stimuli). YNH listeners exhibited near-perfect performance for the unmodified (99.8%) and C80 (92.9%) stimuli and maintained good performance for the E20 stimuli (70.2%). CI users exhibited poorer average performance than YNH listeners for the Full stimuli (72.3%) and proportionally larger reductions in performance for the C80 stimuli (41.8%) and E20 stimuli (29.0%). Findings suggest that CI users have difficulty identifying vowels on the basis of spectral cues in the absence of duration cues, and have limited access to brief dynamic spectral cues. Error analyses suggest that CI users may rely strongly on vowel duration cues when those cues are available.

Multi-site diagnosis and management of 260 patients with auditory neuropathy/dys-synchrony (auditory neuropathy spectrum disorder).

Test results and management data are summarized for 260 patients with diagnoses of Auditory Neuropathy Spectrum Disorder (ANSD). Hearing aids were tried in 85 of these patients, and 49 patients tried cochlear implants. Approximately 15% reported some benefit from hearing aids for language learning, while improvement in speech comprehension and language acquisition was reported in 85% of patients who were implanted. Approximately 5% (13/260) of the total population developed normal speech and language without intervention. Patients were diagnosed at our laboratory (n=66) or referred from other sites (n=194), and all showed absent/grossly abnormal auditory brainstem responses (ABR), often 'ringing' cochlear microphonics, and the presence or history of otoacoustic emissions. Etiologies and co-existing conditions included genetic (n=41), peripheral neuropathies (n=20), perinatal jaundice and/or anoxia and/or prematurity (n=74). These patients comprise 10% or more of hearing impaired patients; their language acquisition trajectories are generally unpredictable from their audiograms.