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Despite an extensive literature linking individual differences in phonological processing to reading ability, some adults show normal text comprehension abilities despite poor pseudoword reading (Jackson & Doellinger (2002). Journal of Educational Psychology, 94, 64-78). This study was undertaken to investigate differences between these individuals, termed resilient readers, and proficient readers in performance and degree of lateralization on a variety of single word processing tasks. Participants completed seven divided visual field tasks investigating various aspects of reading. Resilient readers performed less accurately on basic word recognition tasks, but not on the tasks involving semantic access. Resilient readers did not differ from proficient readers on reaction time or lateralization on any of the experimental tasks. These findings are consistent with the hypothesis that skilled phonological decoding is not necessary for reading for meaning in a college population. It is proposed that higher-level semantic information and general world knowledge may allow some readers to compensate for deficiencies in lower-level word recognition processes. © 2007 Springer Science+Business Media B.V.

This study was conducted to verify, prospectively, the ability of an anatomical risk index (ARI) constructed from seven anatomical measures of cerebral volume and perisylvian asymmetry to predict reading ability in 43 children aged 9 to 18. We found that negative ARIs (low cerebral volume and symmetry) were associated with poor reading ability only in children with low processing speed. Regression analysis showed that anatomy, speed, and an interaction term predicted 53% of the variance in real word reading (p < .0001). Leftward perisylvian asymmetry and larger cerebral volumes may support cognitive flexibility in children with low processing speed. [ABSTRACT FROM AUTHOR]

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal system. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex. [ABSTRACT FROM AUTHOR]

Interpersonal communication via the auditory modality is fundamental to normal human development. One of the prominent anatomical specializations supporting this communication is the transverse gyrus of Heschl on the superior surface of the temporal lobe. This gyrus frequently appears duplicated, either by a sulcus indenting the crown of an initially single gyrus (common stem), or by a complete posterior duplication. The frequency of these duplications has been reported to be elevated in populations with learning disabilities and genetic anomalies. The significance of this observation is unclear, however, due to conflicting reports of the base rate of duplication and the location of relevant sulcal landmarks. In this study we report the variation in frequency and location of the sulcal boundaries of Heschl's gyrus in volumetric magnetic resonance imaging scans of 105 normal controls aged 5-65. The major results were as follows: (i) duplications were unstable - the frequency of duplication ranged from 20 to 60% depending on distance from the midline; (ii) common stem duplications were more frequent than posterior duplications, particularly in the right hemisphere. Intra- and interindividual instability in sulcal landmarks pose serious obstacles to the attempt to map behavioral function onto the brain. Novel methods for dealing with structural variation are needed to facilitate the development of valid mapping techniques. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic β-cells. In pancreatic β-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to β-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic β-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic β-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic β-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic β-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic β-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Since May 2022, approximately 2,500 mpox cases have been reported in Los Angeles County (LAC), California. Beginning in May 2023, the LAC Department of Public Health observed a consistent increase in mpox cases after a prolonged period of low incidence. A total of 56 cases were identified during May 4-August 17, 2023. A minority of mpox patients were fully vaccinated (29%). One patient was hospitalized; no deaths were reported. Two cases of reinfection occurred, both of which were associated with mild illness. The increasing number of cases during this period was significant, as few other health departments in the United States reported an increase in mpox cases during the same period. The outbreak spread similarly to the 2022 U.S. mpox outbreak, mainly through sexual contact among gay, bisexual, and other men who have sex with men. Vaccination against mpox became available in June 2022 and has been shown to be effective at preventing mpox disease. This outbreak was substantially smaller than the 2022 mpox outbreak in LAC (2,280 cases); possible explanations for the lower case count include increased immunity provided from vaccination against mpox and population immunity from previous infections. Nonetheless, mpox continues to spread within LAC, and preventive measures, such as receipt of JYNNEOS vaccination, are recommended for persons at risk of Monkeypox virus exposure., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Abraar Karan received funding from the National Institutes of Health. Nicole M. Green reports serving as president of the Southern California Branch of the American Society for Microbiology. Mario J. Pérez reports institutional support from the Ryan White Program Parts A, B, MAI, and EHE and leadership in the National Coalition of STD Directors. No other potential conflicts of interest were disclosed.

Background: Plasmodium falciparum malaria is a leading cause of child mortality in Nigeria. Neonates are born with maternal antibodies from placental transfer which may protect against malaria infection in the first months of life. The IgG dynamics of the transition from passively transferred antimalarial antibodies to actively acquired IgG from natural exposure have not been well elucidated., Methods: Blood samples collected during a 2018 Nigeria nationwide HIV/AIDS household survey were available for 9,443 children under 5 years of age, with a subset of infants under 2 months of age having maternal samples available (n=41). Samples were assayed for the P. falciparum HRP2 antigen and anti-malarial IgG antibodies. LOESS regression examined the dynamics in IgG response in the first 5 years of life. Correlation with maternal IgG levels was assessed for mother/child pairs., Results: Consistent decreases were observed in median IgG levels against all Plasmodium spp. antigen targets for the first months of life. At a population level, P. falciparum apical membrane antigen-1 (AMA1) and merozoite surface protein-1 19kD (PfMSP1) IgG decreased during the first 12 months of life before reaching a nadir, whereas IgGs to other targets only declined for the first 4 months of life. Seropositivity showed a similar decline with the lowest seropositivity against AMA1 and PfMSP1 at 10-12 months, though remaining above 50% during the first 2 years of life in higher transmission areas. No protective association was observed between IgG positivity and P. falciparum infection in infants. Maternal antibody levels showed a strong positive correlation with infant antibody levels for all P. falciparum antigens from birth to 2 months of age, but this correlation was lost by 6 months of age., Discussion: Maternally transferred anti-malarial IgG antibodies rapidly decline during the first 6 months of life, with variations among specific antigens and malaria transmission intensity. From 3-23 months of age, there was a wide range in IgG levels for the blood-stage antigens indicating high individual variation in antibody production as children are infected with malaria. Non- falciparum species-specific antigens showed similar patterns in waning immunity and correlation with paired mother's IgG levels compared to P. falciparum antigens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leonard, Uhomoibhi, Abubakar, Ogunniyi, Mba, Greby, Okoye, Iriemenam, Ihekweazu, Steinhardt, Rogier and NMS4 Technical Working Group.)

Plasmodium falciparum (Pf) is the dominant malaria parasite in Nigeria though P. vivax (Pv), P. ovale (Po), and P. malariae (Pm) are also endemic. Blood samples (n = 31,234) were collected from children aged 0-14 years during a 2018 nationwide HIV survey and assayed for Plasmodium antigenemia, Plasmodium DNA, and IgG against Plasmodium MSP1-19 antigens. Of all children, 6.6% were estimated to have Pm infection and 1.4% Po infection with no Pv infections detected. The highest household wealth quintile was strongly protective against infection with Pm (aOR: 0.11, 95% CI: 0.05-0.22) or Po (aOR= 0.01, 0.00-0.10). Overall Pm seroprevalence was 34.2% (95% CI: 33.3-35.2) with lower estimates for Po (12.1%, 11.6-12.5) and Pv (6.3%, 6.0-6.7). Pm seropositivity was detected throughout the country with several local government areas showing >50% seroprevalence. Serological and DNA indicators show widespread exposure of Nigerian children to Pm with lower rates to Po and Pv., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background Unplanned hospitalizations are common in patients with cardiovascular disease. The "Triage Heart Failure Risk Status" (Triage-HFRS) algorithm in patients with cardiac implantable electronic devices uses data from up to 9 device-derived physiological parameters to stratify patients as low/medium/high risk of 30-day heart failure (HF) hospitalization, but its use to predict all-cause hospitalization has not been explored. We examined the association between Triage-HFRS and risk of all-cause, cardiovascular, or HF hospitalization. Methods and Results A prospective observational study of 435 adults (including patients with and without HF) with a Medtronic Triage-HFRS-enabled cardiac implantable electronic device (cardiac resynchronization therapy device, implantable cardioverter-defibrillator, or pacemaker). Cox proportional hazards models explored association between Triage-HFRS and time to hospitalization; a frailty term at the patient level accounted for repeated measures. A total of 274 of 435 patients (63.0%) transmitted ≥1 high HFRS transmission before or during the study period. The remaining 161 patients never transmitted a high HFRS. A total of 153 (32.9%) patients had ≥1 unplanned hospitalization during the study period, totaling 356 nonelective hospitalizations. A high HFRS conferred a 37.3% sensitivity and an 86.2% specificity for 30-day all-cause hospitalization; and for HF hospitalizations, these numbers were 62.5% and 85.6%, respectively. Compared with a low Triage-HFRS, a high HFRS conferred a 4.2 relative risk of 30-day all-cause hospitalization (8.5% versus 2.0%), a 5.0 relative risk of 30-day cardiovascular hospitalization (3.6% versus 0.7%), and a 7.7 relative risk of 30-day HF hospitalization (2.0% versus 0.3%). Conclusions In patients with cardiac implantable electronic devices, remotely monitored Triage-HFRS data discriminated between patients at high and low risk of all-cause hospitalization (cardiovascular or noncardiovascular) in real time.

Poor management of health care waste poses a serious threat to the health of health care workers, patients and communities. In developing countries, adequate health care waste management (HCWM) is often a challenge. To address this, the Zambian Health Services Improvement Project with HCWM as a component, was implemented in five Zambian provinces (Luapula, Muchinga, Northern, North-Western and Western Provinces), under which this cross-sectional study was conducted to identify the knowledge, attitudes, and practices of health care workers on HCWM. Fifty government hospitals and health posts from five provinces in Zambia were included in the study. Data was collected using a mixed-methods approach, which included surveys with health care workers (n = 394), in-depth interviews (n = 47) with health officials at the provincial, district, and facility levels, and observational checklists (n = 86). Overall, knowledge of proper waste segregation was average (mean knowledge score 4.7/ 7). HCWM knowledge varied significantly by job position (p = 0.02) and not by facility level, years of service, nor prior training. Only 37.3% of respondents recalled having received any sort of HCWM training. Poor waste segregation practice was found as only 56.9% of the facilities used an infectious waste bag (yellow, red or orange bin liner) and a black bag for general waste. This study revealed that only 43% of facilities had a functional incinerator on site for infectious waste treatment. Needle sticks were alarmingly high with 31.3% of all respondents reporting a prior needle stick. The system of HCWM remains below national and international standards in health facilities in Zambia. It is imperative that all health care workers undergo comprehensive HCWM training and sufficient health care waste commodities are supplied to all health facility levels in Zambia., Competing Interests: The authors declare that no competing interests exist., (Copyright: © 2022 Leonard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The majority of symptomatic malaria in sub-Saharan Africa is caused by Plasmodium falciparum . Infection with Plasmodium ovale is often not recorded and not considered clinically relevant. Here, we describe 8 cases of P ovale infection from 3 African countries-all of which were misdiagnosed at the presenting health facility., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting., Methods: The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual's RDT results. Dose-response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey., Results: Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively)., Conclusions: There is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings., (© 2022. The Author(s).)

Background: Determining malaria transmission within regions of low, heterogenous prevalence is difficult. A variety of malaria tests exist and range from identification of diagnostic infection to testing for prior exposure. This study describes the concordance of multiple malaria tests using data from a 2015 household survey conducted in Ethiopia., Methods: Blood samples (n=2279) from 3 regions in northern Ethiopia were assessed for Plasmodium falciparum and Plasmodium vivax by means of microscopy, rapid diagnostic test, multiplex antigen assay, and multiplex assay for immunoglobulin G (IgG) antibodies. Geospatial analysis was conducted with spatial scan statistics and kernel density estimation to identify malaria hot spots by different test results., Results: The prevalence of malaria infection was low (1.4% by rapid diagnostic test, 1.0% by microscopy, and 1.8% by laboratory antigen assay). For P. falciparum, overlapping spatial clusters for all tests and an additional 5 unique IgG clusters were identified. For P. vivax, clusters identified with bead antigen assay, microscopy, and IgG partially overlapped., Conclusions: Assessing the spatial distribution of malaria exposure using multiple metrics can improve the understanding of malaria transmission dynamics in a region. The relative abundance of antibody clusters indicates that in areas of low transmission, IgG antibodies are a more useful marker to assess malaria exposure., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia. This study investigated whether mixed infections were missed by microscopy from a 2017 therapeutic efficacy study at two health facilities in Ethiopia. All patients (N = 304) were initially classified as having single-species P. falciparum (n = 148 samples) or P. vivax infections (n = 156). Dried blood spots were tested for Plasmodium antigens by bead-based multiplex assay for pan-Plasmodium aldolase, pan-Plasmodium lactate dehydrogenase, P. vivax lactate dehydrogenase, and histidine-rich protein 2. Of 304 blood samples, 13 (4.3%) contained both P. falciparum and P. vivax antigens and were analyzed by polymerase chain reaction for species-specific DNA. Of these 13 samples, five were confirmed by polymerase chain reaction for P. falciparum/P. vivax co-infection. One sample, initially classified as P. vivax by microscopy, was found to only have Plasmodium ovale DNA. Plasmodium falciparum/P. vivax mixed infections can be missed by microscopy even in the context of a therapeutic efficacy study with multiple trained readers.

Background: Diarrhoea is a major health issue in both humans and animals and may be caused by bacterial, viral and fungal infections. Previous studies highlighted excellent activity of Newtonia buchananii and N. hildebrandtii leaf extracts against bacterial and fungal organisms related to diarrhoea-causing pathogens. The aim of this study was to isolate the compound(s) responsible for antimicrobial activity and to investigate efficacy of the extracts and purified compound against bacterial biofilms., Methods: The acetone extract of N. buchananii leaf powder was separated by solvent-solvent partitioning into eight fractions, followed by bioassay-guided fractionation for isolation of antimicrobial compounds. Antibacterial activity testing was performed using a broth microdilution assay. The cytotoxicity was evaluated against Vero cells using a colorimetric MTT assay. A crystal violet method was employed to test the inhibitory effect of acetone, methanol: dichloromethane and water (cold and hot) extracts of N. buchananii and N. hildebrandtii leaves and the purified compound on biofilm formation of Pseudomonas aeruginosa, Escherichia coli, Salmonella Typhimurium, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus., Results: Myricetin-3-o-rhamnoside (myricitrin) was isolated for the first time from N. buchananii. Myricitrin was active against B. cereus, E. coli and S. aureus (MIC = 62.5 μg/ml in all cases). Additionally, myricitrin had relatively low cytotoxicity with IC 50  = 104 μg/ml. Extracts of both plant species had stronger biofilm inhibitory activity against Gram-positive than Gram-negative bacteria. The most sensitive bacterial strains were E. faecalis and S. aureus. The cold and hot water leaf extracts of N. buchananii had antibacterial activity and were relatively non-cytotoxic with selectivity index values of 1.98-11.44., Conclusions: The purified compound, myricitrin, contributed to the activity of N. buchananii but it is likely that synergistic effects play a role in the antibacterial and antibiofilm efficacy of the plant extract. The cold and hot water leaf extracts of N. buchananii may be developed as potential antibacterial and antibiofilm agents in the natural treatment of gastrointestinal disorders including diarrhoea in both human and veterinary medicine.

Background: Urinary tract infections (UTIs) caused by opportunistic pathogens are among the leading health challenges globally. Most available treatment options are failing as a result of antibiotic resistance and adverse effects. Natural sources such as plants may serve as promising alternatives., Methods: Compounds were isolated from the South African weed Chromolaena odorata through column chromatography. Purified compounds were tested for antimicrobial activity using the p-iodonitrotetrazolium chloride (INT) colorimetric method, against uropathogenic Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Aspergillus fumigatus and Cryptococcus neoformans. Anti-biofilm, anti-adhesion and metabolic inhibition activities were investigated against selected strains. Safety of the compounds was determined against Vero monkey kidney, C3A human liver and colon (Caco2) cells., Results: Four compounds identified as pectolinaringenin (1), (±)-4',5,7-trimethoxy flavanone (2), 5-hydroxy-3,7,4'-trimethoxyflavone (3) and 3,5,7-trihydroxy-4'-methoxyflavone) (4) were isolated. Minimum inhibitory concentration (MIC) varied between 0.016 and 0.25 mg/mL. Compounds 2 and 3 showed promising antimicrobial activity against E. coli, S. aureus, K. pneumoniae, A. fumigatus and C. neoformans with MIC between 0.016 and 0.125 mg/mL, comparable to gentamicin, ciprofloxacin and amphotericin B used as positive controls. Compounds 2 and 3 showed good anti-biofilm and metabolic inhibition activities against E. coli and S. aureus but weak anti-adhesion activity against the organisms. Low toxicity with selectivity indexes between 1 and 12.625 were recorded with the compounds, indicating that the compounds were rather toxic to the microbial strains and not to the human and animal cells., Conclusion: Pharmacological activities displayed by compounds 2 and 3 isolated from C. odorata and low toxicity recorded credits it as a potential lead for the development of useful prophylactic treatments and anti-infective drugs against UTIs. Although known compounds, this is the first time these compounds have been isolated from the South African weed C. odorata and tested for antimicrobial, anti-biofilm, metabolic inhibition and anti-adhesion activities.

Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice. Using a novel sensitive RNAscope in situ hybridization, we detected CB2R mRNA expression in VTA DA neurons in wildtype and DAT-Cnr2 cKO heterozygous but not in the homozygous DAT-Cnr2 cKO mice. Here we report that the deletion of CB2Rs in dopamine neurons enhances motor activities, modulates anxiety and depression-like behaviors and reduces the rewarding properties of alcohol. Our data reveals that CB2Rs are involved in the tetrad assay induced by cannabinoids which had been associated with CB1R agonism. GWAS studies indicates that the CNR2 gene is associated with Parkinson's disease and substance use disorders. These results suggest that CB2Rs in dopaminergic neurons may play important roles in the modulation of psychomotor behaviors, anxiety, depression, and pain sensation and in the rewarding effects of alcohol and cocaine.

Purpose: Patient-reported outcome measures (PROMs) have become an important part of routine auditing of outcomes in spinal surgery in the UK. PROMs can be used to help assess the quality of care provided by surgical units by determining the comparative health status of patients, before and after surgery. This study was designed to review the PROMs used to assess outcomes in spinal surgery and to determine if they are fit for the purpose., Methods: A systematic literature search was undertaken to identify studies that reported PROMs data following lumbar spinal surgery. The PROMs that were used in each study were recorded and a separate search was undertaken to determine the evidence regarding the validity of each measure., Results: The initial search identified 1142 abstracts, which were reduced through de-duplication, filtering and review to 58 articles, which were retrieved and reviewed in full. The search identified that the majority of studies used either the Oswestry Disability Index (ODI), SF-36, Roland-Morris Disability Questionnaire (RMDQ) and EQ-5D along with visual analogue scales or numeric rating scales for back and leg pain., Conclusions: The consistent use of PROMs supports the comparison of outcomes from different studies, although there was minimal evidence regarding the specificity and sensitivity of these measures for use with lumbar spinal patients. Our review highlights the need to determine a consensus regarding the use and reporting of outcome measures within the lumbar spine literature.

The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink-Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat׳s MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat׳s MD-projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. © 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The genus Warburgia (Canellaceae) is represented by several medicinal trees found exclusively on the African continent. Traditionally, extracts and products produced from Warburgia species are regarded as important natural African antibiotics and have been used extensively as part of traditional healing practices for the treatment of fungal, bacterial and protozoal infections in both humans and animals. We here aim to collate and review the fragmented information on the ethnobotany, phytochemistry and biological activities of ethnomedicinally important Warburgia species and present recommendations for future research., Materials and Methods: Peer-reviewed articles using "Warburgia" as search term ("all fields") were retrieved from Scopus, ScienceDirect, SciFinder and Google Scholar with no specific time frame set for the search. In addition, various books were consulted that contained botanical and ethnopharmacological information., Results: The ethnopharmacology, phytochemistry and biological activity of Warburgia are reviewed. Most of the biological activities are attributed to the drimane sesquiterpenoids, including polygodial, warburganal, muzigadial, mukaadial and ugandensial, flavonoids and miscellaneous compounds present in the various species. In addition to anti-infective properties, Warburgia extracts are also used to treat a wide range of ailments, including stomach aches, fever and headaches, which may also be a manifestation of infections. The need to record anecdotal evidence is emphasised and conservation efforts are highlighted to contribute to the protection and preservation of one of Africa's most coveted botanical resources., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The current study investigated behavioral correlates of structural asymmetry of the insula, and traditional perisylvian language regions, in a large sample of young adults (N=200). The findings indicated (1) reliable leftward surface area asymmetry of the anterior insula, (2) association of this asymmetry with divided visual field lateralization of visual word recognition, and (3) modulation of the correlation of structural and linguistic asymmetry by consistency of hand preference. Although leftward asymmetry of cortical surface area was observed for the anterior insula, pars opercularis and triangularis, and planum temporale, only the anterior insula asymmetry was associated with lateralized word recognition. We interpret these findings within the context of recent structural and functional findings about the human insula. We suggest that leftward structural lateralization of earlier developing insular cortex may bootstrap asymmetrical functional lateralization even if the insula is only a minor component of the adult language network., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The three anterior temporobasal (aTB) sulci, which are the collateral, rhinal, and occipitotemporal sulci, contribute to the morphology of memory-related structures and are important landmarks for neuroimaging. Prevalence of inter-connections among these sulci may distinguish healthy adults and individuals with memory-related disorders (Kim et al. Neurology 70:2159-2165, 2008; Zhan et al. Hum Brain Mapp 30:874-882, 2009). However, methods for quantifying the existence and nature of such connections are vague and varied, and normative frequencies are inconsistent across studies. Therefore, the goals of the current study are twofold: (1) to develop a reliable method of identifying aTB sulci and their interconnections based on surface renderings generated from serial magnetic resonance images (MRIs). This protocol includes training materials and a rating log (see supplementary materials) that can be disseminated and applied by other researchers. (2) To determine the prevalence of interconnections among the three aTB sulci in a large sample of healthy adults (200 undergraduate students), which can be used as normative data for future comparison with clinical samples. Notably, the resulting protocol, called the Sulcal Classification Rating Protocol for anterior Temporobasal sulci, distinguishes "clear" from "ambiguous" connections. When only clear connections are included, our prevalence rates are consistent with post-mortem findings of Ono et al. (Atlas of the Cerebral Sulci. Thieme Medical Publishers, Inc., New York, 1990); when both clear and ambiguous connections are counted as a connection, our results largely replicate MRI-based findings (e.g., Kim et al. Neurology 70:2159-2165, 2008). We propose that systematic variations in rater classification of ambiguous connections could explain discrepancies in the literature.

Individual differences in reading and cerebral lateralisation were investigated in 200 college students who completed reading assessments and divided visual field word recognition tasks, and received a structural MRI scan. Prior studies on this data set indicated that little variance in brain-behaviour correlations could be attributed to the effects of sex and handedness variables (Chiarello, Welcome, Halderman, & Leonard, 2009; Chiarello, Welcome, Halderman, Towler, et al., 2009; Welcome et al., 2009). Here a more bottom-up approach to behavioural classification (cluster analysis) was used to explore individual differences that need not depend on a priori decisions about relevant subgroups. The cluster solution identified four subgroups of college age readers with differing reading skill and visual field lateralisation profiles. These findings generalised to measures that were not included in the cluster analysis. Poorer reading skill was associated with somewhat reduced VF asymmetry, while average readers demonstrated exaggerated RVF/left hemisphere advantages. Skilled readers had either reduced asymmetries, or asymmetries that varied by task. The clusters did not differ by sex or handedness, suggesting that there are identifiable sources of variance among individuals that are not captured by these standard participant variables. All clusters had typical leftward asymmetry of the planum temporale. However, the size of areas in the posterior corpus callosum distinguished the two subgroups with high reading skill. A total of 17 participants, identified as multivariate outliers, had unusual behavioural profiles and differed from the remainder of the sample in not having significant leftward asymmetry of the planum temporale. A less buffered type of neurodevelopment that is more open to the effects of random genetic and environmental influences may characterise such individuals.

In a recent critique Boles and Barth (2011) argue that their prior study investigating asymmetry/performance relationships (Boles, Barth, & Merrill, 2008) uncovered the "true" association (i.e., negative correlation) between lateralization of visual lexical processes and word recognition performance. They contend that our study reporting positive correlations of lexical asymmetry and reading performance (Chiarello et al., 2009) was flawed and hence inconclusive. In this response we address the two major objections raised by Boles and Barth (2011) regarding our selection of tasks and asymmetry measures. We conclude that the Boles and Barth principle of task purity is not relevant to the stated aims of our investigation, and that our linear regression method of measuring asymmetry is valid given the high level of accuracy for the tasks we reported. Because the aims of each investigation differed, we argue that it is unwise to attempt to fit each study into the framework favored by Boles and Barth (2011)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

Resilient readers are characterized by impaired phonological processing despite skilled text comprehension. We investigated orthographic and semantic processing in resilient readers to examine mechanisms of compensation for poor phonological decoding. Performance on phonological (phoneme deletion, pseudoword reading), orthographic (orthographic choice, orthographic analogy), and semantic (semantic priming, homograph resolution) tasks was compared between resilient, poor and proficient readers. Asymmetry of the planum temporale was investigated in order to determine whether atypical readers showed unusual morphology in this language-relevant region. Resilient readers showed deficits on phonological tasks similar to those shown by poor readers. We obtained no evidence that resilient readers compensate via superior orthographic processing, as they showed neither exceptional orthographic skill nor increased reliance on orthography to guide pronunciation. Resilient readers benefited more than poor or proficient readers from semantic relationships between words and experienced greater difficulty when such relationships were not present. We suggest, therefore, that resilient readers compensate for poor phonological decoding via greater reliance on word meaning relationships. The reading groups did not differ in mean asymmetry of the planum temporale. However, resilient readers showed greater variability in planar asymmetry than proficient readers. Poor readers also showed a trend towards greater variability in planar asymmetry, with more poor readers than proficient readers showing extreme asymmetry. Such increased variability suggests that university students with less reading skill display less well regulated brain anatomy than proficient readers., (Copyright 2010 Elsevier Inc. All rights reserved.)

Aims: The antibiofilm activity of extracts obtained from selected herbs, spices, beverages and commercially important medicinal plants was investigated on Listeria monocytogenes., Methods and Results: The growth and development of the biofilm was assessed using the crystal violet (CV) assay. The respiratory activity was assessed using the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The majority of extracts tested prevented cell adhesion to the polyvinyl chloride (PVC) surface. Seven of the 15 extracts reduced biofilm adhesion of both the clinical and the type strains by at least 50%. In contrast, inhibition of a preformed biofilm was more difficult to achieve, with only three extracts (Rosmarinus officinalis, Mentha piperita and Melaleuca alternifolia) inhibiting the growth of both strains by at least 50%., Conclusions: Although most extracts were able to reduce initial cell attachment, inhibition of growth in a preformed biofilm was more difficult to achieve., Significance and Impact of the Study: The ability to reduce biofilm biomass as shown by several plant extracts warrants further investigation to explore the use of natural products in antibiofilm adhesion.

Many structural brain asymmetries accompany left hemisphere language dominance. For example, the cingulate sulcus is larger in the medial cortex of the right hemisphere, while the more dorsal paracingulate sulcus is larger on the left. The functional significance of these asymmetries is unknown because fMRI studies rarely attempt to localize activation to specific sulci, possibly due to difficulties in consistent sulcal identification. In medial cortex, for example, there are many regions of partial sulcal overlap where MRI images do not provide sufficient information to unambiguously distinguish a paracingulate sulcus from a displaced anterior cingulate segment. As large samples of postmortem material are rarely available for cytoarchitectural studies of sulcal variation, we have investigated the effect of variation in boundary and sulcal definition on paracingulate asymmetry in the MRI scans of 200 healthy adults (100 men, 100 women). Although women displayed a reliable asymmetry in the size of the paracingulate sulcus, regardless of boundary definition or technique, asymmetry was greatest when (1) the measurement was limited to the midcingulate region between the genu and the anterior commissure; and (2) the more dorsal of two overlapping sulci was always classified as a paracingulate sulcus (rather than as a displaced cingulate segment). The fact that paracingulate asymmetry is maximal in the midcingulate region suggests that this region may play a particular role in hemispheric specialization for language. Future work should investigate the structural and functional correlates of sulcal variation in this region.

There are substantial individual differences in the size and shape of the corpus callosum and such differences are thought to relate to behavioral lateralization. We report findings from a large scale investigation of relationships between brain anatomy and behavioral asymmetry on a battery of visual word recognition tasks. A sample of 200 individuals was divided into groups on the basis of sex and consistency of handedness. We investigated differences between sex/handedness groups in callosal area and relationships between callosal area and behavioral predictors. Sex/handedness groups did not show systematic differences in callosal area or behavioral asymmetry. However, the groups differed in the relationships between area of the corpus callosum and behavioral asymmetry. Among consistent-handed males, callosal area was negatively related to behavioral laterality. Among mixed-handed males and consistent-handed females, behavioral laterality was not predictive of callosal area. The most robust relationship was observed in mixed-handed females, in whom behavioral asymmetry was positively related to callosal area. Our study demonstrates the importance of considering brain/behavior relationships within sub-populations, as relationships between behavioral asymmetry and callosal anatomy varied across subject groups.

Plectranthus ecklonii Benth. is traditionally used in South Africa for treating stomach aches, nausea, vomiting and meningitis. Bioassay-guided fractionation of the ethyl acetate extract of the plant led to the isolation of two known compounds, parvifloron D and parvifloron F, neither of which has been previously reported for this species. The compounds exhibited minimum inhibitory concentrations of 15.6 and 31.2 microg/mL, respectively against Listeria monocytogenes, whereas the values against a drug-sensitive strain of Mycobacterium tuberculosis were 190 and 95 microg/mL, respectively. The ethyl acetate extract of P. ecklonii and its isolated compounds were tested for their activity on tyrosinase inhibition. The concentration at which half the tyrosinase activity was inhibited (IC50) by the extract was found to be 61.7 +/- 2.7 microg/mL. The antibacterial activity of the extract and its isolated compounds correlates with the traditional use of the plant for various ailments such as stomach aches, diarrhea and skin diseases. The fifty percent inhibitory concentrations of parvifloron D and parvifloron F against vero cell lines were found to be 2.9 microg/mL and 1.6 microg/mL, respectively. This is the first report of the bioactivity of P. ecklonii extract and its constituents.

Is it advantageous to be strongly lateralized? The current study investigated this question by examining the relationship between visual field asymmetries for lexical tasks and reading performance in a sample of 200 young adults. Larger visual field asymmetries were associated with better reading performance, but this relationship was obtained primarily in those with strong and consistent hand preferences. Among mixed handers, variation in visual field asymmetry accounted for little or no variance in reading skill. In addition, correlations between visual field asymmetry and reading performance were observed for word recognition tasks, but not for tasks requiring controlled semantic retrieval. The results are consistent with the idea that consistent and mixed handers may represent differing neurobehavioral populations. Because greater lateralization was associated with better reading skill only for consistent handers, reduced behavioral asymmetry cannot be assumed to be a risk factor for reading dysfunction in the population as a whole.

Recent findings suggest that neural representations of semantic knowledge contain information about category, modality, and attributes. Although an object's category is defined according to shared attributes that uniquely distinguish it from other category members, a clear dissociation between visual attribute and category representation has not yet been reported. We investigated the contribution of category (living and nonliving) and visual attribute (global form and local details) to semantic representation in the fusiform gyrus. During functional magnetic resonance imaging (fMRI), 40 adults named pictures of animals, tools, and vehicles. In a preliminary study, identification of objects in these categories was differentially dependent on global versus local visual feature processing. fMRI findings indicate that activation in the lateral and medial regions of the fusiform gyrus distinguished stimuli according to category, that is, living versus nonliving, respectively. In contrast, visual attributes of global form (animals) were associated with higher activity in the right fusiform gyrus, while local details (tools) were associated with higher activity in the left fusiform gyrus. When both global and local attributes were relevant to processing (vehicles), cortex in both left and right medial fusiform gyri was more active than for other categories. Taken together, results support distinctions in the role of visual attributes and category in semantic representation.

The authors report findings of a large-scale, multitask investigation of sex differences in both structural asymmetries and lateralization of word reading. Two hundred participants were tested in eight divided visual field lexical tasks, and each received a structural magnetic resonance imaging scan. The authors examined whether there was evidence for sex differences in overall measures of neuroanatomical and behavioral lateralization, in specific language tasks and brain regions, and in variation in asymmetry within and across tasks and brain regions. There was very little evidence for sex differences on any behavioral measure. The few indications of sex differences in the current report accounted for 2% or less of the individual variation in asymmetry and could not be replicated in independent subsamples. No sex differences were observed in the asymmetry of structures in Broca's and Wernicke's areas such as pars triangularis, pars opercularis, the planum temporale, planum parietale, or Heschl's gyrus. There were also no sex differences in the variability of neuroanatomical asymmetries within or between brain regions. However, a significant relationship between planum temporale and behavioral asymmetry was restricted to men.

Background: The technique of X-ray-based dual photon absorptiometry (DXA) is frequently used in children for the detection of changes in bone mass or body composition. Such changes can only be considered real if the uncertainties arising from the measurement technique are exceeded., Objective: Our objectives were twofold: (1) to determine the reproducibility of bone mineral density (BMD) measurements in children at the spine and the hip and from the whole body, as well as of whole-body measurements of mineral mass, lean body mass and fat mass in children; and (2) to estimate, from the measured precision, the time interval that needs to elapse before a statistically significant change in a DXA variable can be detected., Materials and Methods: The reproducibility of techniques for the measurement of BMD and body composition using DXA was measured in 15 young children (9 girls and 6 boys) and 17 older children (9 girls and 8 boys)., Results: Reproducibility was derived from the standard deviation of three repeated measurements of spine BMD, total hip BMD, whole-body BMD (WBBMD), whole-body bone mineral content (WBBMC), lean mass and fat mass. Technique precision was better than 0.01 g cm(-2) for spine BMD and for WBBMD. Hip BMD measurements were slightly less precise, particularly in younger children (0.013 g cm(-2)). For body composition variables, technique precision was 13 g for WBBMC, 201 g for lean body mass and 172 g for fat mass in younger children. Technique precision for older children was 18 g, 251 g and 189 g for the corresponding variables. Predictions showed that the absence of a normal increase in WBBMC in a small-for-age girl could be established after 12 months. For spine BMD, a significant increase should be observable after 6 months for boys over the age of 11 years. For younger boys, more than 12 months has to elapse before anticipated changes can be detected with confidence., Conclusion: The time intervals required to elapse before decisions can be made concerning the significance of observed differences between successive measurements of BMD or body composition in children depend upon the age of the child.

As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

Biological and behavioral differences between the sexes range from obvious to subtle or nonexistent. Neuroanatomical differences are particularly controversial, perhaps due to the implication that they might account for behavioral differences. In this sample of 200 men and women, large effect sizes (Cohen's d > 0.8) were found for sex differences in total cerebral gray and white matter, cerebellum, and gray matter proportion (women had a higher proportion of gray matter). The only one of these sex differences that survived adjustment for the effect of cerebral volume was gray matter proportion. Individual differences in cerebral volume accounted for 21% of the difference in gray matter proportion, while sex accounted for an additional 4%. The relative size of the corpus callosum was 5% larger in women, but this difference was completely explained by a negative relationship between relative callosal size and cerebral volume. In agreement with Jancke et al., individuals with higher cerebral volume tended to have smaller corpora callosa. There were few sex differences in the size of structures in Broca's and Wernicke's area. We conclude that individual differences in brain volume, in both men and women, account for apparent sex differences in relative size.

The planum temporale is a region on the posterior surface of the temporal lobe that exhibits robust leftward structural asymmetry, which has been linked to verbal ability in children and adults. Traditionally, structural asymmetry has been quantified with manual assessment of high resolution MRI scans. Such measures require subjective and frequently unreliable determination of highly variable anatomical boundaries. Methodological developments in automated image processing (voxel-based morphometry - VBM) offer the opportunity to obtain objective and reliable measures of structural variation. This study examined the extent to which a VBM measure of gray matter asymmetry in the posterior superior temporal gyrus (pSTG) characterized the same individual variation as a manual measure of planum temporale asymmetry in 99 healthy adults and 39 typically developing children. Planum temporale asymmetry was significantly correlated with pSTG gray matter asymmetry in the samples of adults and children. As a measure of validity we examined the extent to which the VBM measure of pSTG gray matter asymmetry predicted measures of verbal ability that were associated with the manual measure of planum temporale asymmetry in the same children. The two asymmetry measures predicted the same variance in verbal ability. The automated measure of pSTG gray matter asymmetry predicted additional significant variance in verbal ability, however. In addition, a posterior STS region was also identified that significantly predicted verbal ability. These results demonstrate significant advantages of an automated voxel-based measure over a manual measure of planum temporale asymmetry.

Healthy older adults frequently report word-finding difficulties, yet the underlying cause of these problems is not well understood. This study examined whether age-related changes in word retrieval are related to changes in areas of the frontal lobes thought to subserve word retrieval or changes in areas of the inferior temporal lobes thought to be involved in semantic knowledge. Twenty younger and 20 older healthy adults named aloud photographs during event-related fMRI. Results showed that in the face of equivalent naming accuracy, older adults activated a larger frontal network than younger adults during word retrieval, but there were no activity differences between groups in the fusiform gyrus, suggesting that the substrates for word retrieval but not for semantic knowledge change with aging. Additionally, correlations between BOLD response and naming accuracy and response latency were found in several frontal and subcortical regions in older adults. Findings are discussed in the context of possible compensatory mechanisms invoked to maintain performance in healthy aging, and suggest that increased involvement of the right hemisphere is not universally beneficial to performance.

In previous work, the authors found that an anatomical risk index created from the combination of 7 neuroanatomical measures predicted reading and oral language skills in individuals with learning disabilities. Individuals with small auditory brain structures and reduced asymmetry had more deficits than those with large structures and exaggerated asymmetry. In the present study, the same anatomical index predicted reading and other cognitive abilities in 45 individuals with chronic schizophrenia. The anatomical risk index was significantly associated with broad cognitive ability (Pearson r = .53, p < .0001), reading comprehension (r = .58, p < .0001), and a measure of nonverbal reasoning (r = .39, p < .01), but not with age, parental socioeconomic status, symptom measures, alcohol use, or processing speed. These findings support the prediction that reduced size and asymmetry in temporal lobe auditory cortex and cerebellum may not be specific risk factors for schizophrenia but for cognitive deficits that characterize a broad spectrum of developmental disorders.

Developmental language disorders are characterized by a maturational trajectory that deviates or lags that of normal children. Given the wide variation in the rate of normal language development, diagnosis and classification of these disorders poses severe problems for the clinician. Our laboratory has been searching for anatomical signatures that could aid the development of a neurobiologically based classification. Quantitative analysis of the magnetic resonance imaging (MRI) brain scans of a series of samples of children and adults with reading and language disorders has identified two clusters with contrasting anatomical and reading profiles. Individuals with small symmetrical brain structures tend to have deficits in multiple domains of written and oral language whereas those with larger asymmetrical structures are more likely to have the isolated phonological deficits seen in adults with compensated dyslexia. Surprisingly, the anatomical risk factors that define these clusters do not form a continuum of increasing severity but deviate in opposite directions from normal. Individuals with moderate brain size and asymmetry typically demonstrate the best overall performance. Further research should determine if phonological impairments in the two clusters are associated with differing genetic and environmental risk factors requiring different types of intervention.