Hearing Aid Amplification Improves Postural Control for Older Adults With Hearing Loss When Other Sensory Cues Are Impoverished.

Recent studies suggest that sound amplification via hearing aids can improve postural control in adults with hearing impairments. Unfortunately, only a few studies used well-defined posturography measures to assess balance in adults with hearing loss with and without their hearing aids. Of these, only two examined postural control specifically in the elderly with hearing loss. The present study examined the impact of hearing aid use on postural control during various sensory perturbations in older adults with age-related hearing loss. Thirty individuals with age-related hearing impairments and using hearing aids bilaterally were tested. Participants were asked to perform a modified clinical sensory integration in balance test on a force platform with and without hearing aids. The experiment was conducted in the presence of a broadband noise ranging from 0.1 to 4 kHz presented through a loudspeaker. As expected, hearing aid use had a beneficial impact on postural control, but only when visual and somatosensory inputs were both reduced. Data also suggest that hearing aid use decreases the dependence on somatosensory input for maintaining postural control. This finding can be of particular importance in older adults considering the reduction of tactile and proprioceptive sensitivity and acuity often associated with aging. These results provide an additional argument for encouraging early hearing aid fitting for people with hearing loss.

Earbox, an open tool for high-throughput measurement of the spatial organization of maize ears and inference of novel traits.

BACKGROUND: Characterizing plant genetic resources and their response to the environment through accurate measurement of relevant traits is crucial to genetics and breeding. Spatial organization of the maize ear provides insights into the response of grain yield to environmental conditions. Current automated methods for phenotyping the maize ear do not capture these spatial features. RESULTS: We developed EARBOX, a low-cost, open-source system for automated phenotyping of maize ears. EARBOX integrates open-source technologies for both software and hardware that facilitate its deployment and improvement for specific research questions. The imaging platform consists of a customized box in which ears are repeatedly imaged as they rotate via motorized rollers. With deep learning based on convolutional neural networks, the image analysis algorithm uses a two-step procedure: ear-specific grain masks are first created and subsequently used to extract a range of trait data per ear, including ear shape and dimensions, the number of grains and their spatial organisation, and the distribution of grain dimensions along the ear. The reliability of each trait was validated against ground-truth data from manual measurements. Moreover, EARBOX derives novel traits, inaccessible through conventional methods, especially the distribution of grain dimensions along grain cohorts, relevant for ear morphogenesis, and the distribution of abortion frequency along the ear, relevant for plant response to stress, especially soil water deficit. CONCLUSIONS: The proposed system provides robust and accurate measurements of maize ear traits including spatial features. Future developments include grain type and colour categorisation. This method opens avenues for high-throughput genetic or functional studies in the context of plant adaptation to a changing environment.

Cemented humeral stem versus press-fit humeral stem in total shoulder arthroplasty: a systematic review and meta-analysis.

AIMS: The aim of this study was to evaluate the differences in revision and complication rates, functional outcomes, and radiological outcomes between cemented and press-fit humeral stems in primary anatomical total shoulder arthroplasty (TSA). MATERIALS AND METHODS: A comprehensive systematic review and meta-analysis was conducted searching for studies that included patients who underwent primary anatomical TSA for primary osteoarthritis or rheumatoid arthritis. RESULTS: There was a total of 36 studies with 927 cemented humeral stems and 1555 press-fit stems. The revision rate was 5.4% (95% confidence interval (CI) 3.9 to 7.4) at a mean of 89 months for cemented stems, and 2.4% (95% CI 1.1 to 4.7) at a mean of 40 months for press-fit stems. A priori subgroup analysis to control for follow-up periods demonstrated similar revision rates: 2.3% (95% CI 1.1 to 4.7) for cemented stems versus 1.8% (95% CI 1.4 to 2.9) for press-fit stems. Exploratory meta-regression found that longer follow-up was a moderating variable for revision (p = 0.003). CONCLUSION: Cement fixation had similar revision rates when compared to press-fit stems at short- to midterm follow-up. Rotator cuff pathology was a prevalent complication in both groups but is likely not related to fixation type. Overall, with comparable revision rates, possible easier revision, and decreased operative time, humeral press-fit fixation may be an optimal choice for primary anatomical TSA in patients with sufficient bone stock. Cite this article: Bone Joint J 2019;101-B:1107-1114.

Vestibular Function Modulates the Benefit of Hearing Aids in People With Hearing Loss During Static Postural Control.

OBJECTIVES: To evaluate the influence of auditory cues on postural sway in normal-hearing (NH) individuals, hearing-impaired individuals with vestibular impairment (HIVL), or hearing-impaired (HI) individuals without vestibular impairment. DESIGN: Thirty-two participants received a hearing and a vestibular evaluation (vHIT, oVEMP, cVEMP) and then were separated in to three groups (NH, HI, HIVL). All participants had to stand on a force platform in four postural conditions (A: EO/firm, B: EC/firm, C: EO/Foam, D: EC/Foam) under two auditory conditions, with or without auditory cues. RESULTS: Results revealed that first, there was a significant difference between HIVL and both HI and NH groups in conditions C and D without auditory cues. Second, greater improvement for HIVL compared to NH and HI groups in condition C and D was observed with auditory cues. Finally, somatosensory reliance significantly decreased for the HIVL participants using hearing aids compared to NH and HI. CONCLUSIONS: Our results suggest that hearing aids benefit for postural control may be modulated by vestibular function.

Comparative outcomes of outpatient and inpatient total shoulder arthroplasty: an analysis of the Medicare dataset.

AIMS: The aim of the present study was to compare the 30- and 90-day re-admission rates and complication rates of outpatient and inpatient total shoulder arthroplasty (TSA). PATIENTS AND METHODS: The United States Medicare Standard Analytical Files database was questioned to identify patients who had undergone outpatient or inpatient TSA between 2005 and 2012. Patient characteristics were compared between the two groups using chi-squared analysis. Multivariate logistic regression analysis was used to control for differences in baseline patient characteristics and to compare the two groups in terms of post-operative complications within 90 days and re-admission within 30 days and 90 days. RESULTS: A total of 123 347 Medicare subscribers underwent TSA between 2005 and 2012; 3493 (2.8%) had the procedure performed as an outpatient. A significantly greater proportion of patients who underwent TSA as inpatients were women, had a history of smoking, and had a greater incidence of medical comorbidity including diabetes, coronary artery disease, congestive heart failure, and chronic kidney disease (p < 0.05 for all). Re-admission rates were significantly higher for inpatients at both 30 days (0.83% versus 0.60%, p = 0.016, odds ratio 1.8) and 90 days (2.87% versus 2.04%, p < 0.001, odds ratio 1.8). Complications, including thromboembolic events (p < 0.001) and surgical site infection (p = 0.002), were significantly higher in inpatients. CONCLUSION: Patients who underwent TSA on an outpatient basis were overall younger and healthier than those who had inpatient surgery, which suggests that patient selection was taking place. After controlling for age, gender, and medical conditions, patients who underwent TSA as outpatients had lower rates of 30- and 90-day re-admission and a lower rate of complications than inpatients. Cite this article: Bone Joint J 2017;99-B:934-8.

Genomics and public health research: can the state allow access to genomic databases?

Because many diseases are multifactorial disorders, the scientific progress in genomics and genetics should be taken into consideration in public health research. In this context, genomic databases will constitute an important source of information. Consequently, it is important to identify and characterize the State's role and authority on matters related to public health, in order to verify whether it has access to such databases while engaging in public health genomic research. We first consider the evolution of the concept of public health, as well as its core functions, using a comparative approach (e.g. WHO, PAHO, CDC and the Canadian province of Quebec). Following an analysis of relevant Quebec legislation, the precautionary principle is examined as a possible avenue to justify State access to and use of genomic databases for research purposes. Finally, we consider the Influenza pandemic plans developed by WHO, Canada, and Quebec, as examples of key tools framing public health decision-making process. We observed that State powers in public health, are not, in Quebec, well adapted to the expansion of genomics research. We propose that the scope of the concept of research in public health should be clear and include the following characteristics: a commitment to the health and well-being of the population and to their determinants; the inclusion of both applied research and basic research; and, an appropriate model of governance (authorization, follow-up, consent, etc.). We also suggest that the strategic approach version of the precautionary principle could guide collective choices in these matters.

A weight of evidence approach for the assessment of the ototoxic potential of industrial chemicals.

There is accumulating epidemiological evidence that exposure to some solvents, metals, asphyxiants and other substances in humans is associated with an increased risk of acquiring hearing loss. Furthermore, simultaneous and successive exposure to certain chemicals along with noise can increase the susceptibility to noise-induced hearing loss. There are no regulations that require hearing monitoring of workers who are employed at locations in which occupational exposure to potentially ototoxic chemicals occurs in the absence of noise exposure. This project was undertaken to develop a toxicological database allowing the identification of possible ototoxic substances present in the work environment alone or in combination with noise exposure. Critical toxicological data were compiled for chemical substances included in the Quebec occupational health regulation. The data were evaluated only for noise exposure levels that can be encountered in the workplace and for realistic exposure concentrations up to the short-term exposure limit or ceiling value (CV) or 5 times the 8-h time-weighted average occupational exposure limit (TWA OEL) for human data and up to 100 times the 8-h TWA OEL or CV for animal studies. In total, 224 studies (in 150 articles of which 44 evaluated the combined exposure to noise and a chemical) covering 29 substances were evaluated using a weight of evidence approach. For the majority of cases where potential ototoxicity was previously proposed, there is a paucity of toxicological data in the primary literature. Human and animal studies indicate that lead, styrene, toluene and trichloroethylene are ototoxic and ethyl benzene, n-hexane and p-xylene are possibly ototoxic at concentrations that are relevant to the occupational setting. Carbon monoxide appears to exacerbate noise-induced hearing dysfunction. Toluene interacts with noise to induce more severe hearing losses than the noise alone.

Framing genomics, public health research and policy: points to consider.

Genetic information can be used to target interventions that improve health and prevent disease. Indeed, the results of population genomics research could be useful for public health and national pandemic plans. Yet, firm scientific evidence originating from such research and the indicators of the role of health determinants, gene-gene and gene-environment interaction remain to be assessed and validated before being integrated into pandemic plans or public health programmes. It is not clear what is the role of the State in research on the elucidation of the determinants of gene-gene and gene-environment interactions and how, when, and if such data can be accessed and used for such planning. Over a period of 3 years, we sought to address these questions by gathering data and literature relevant to research in public health genomics, preparing issues papers and, finally, consulting with stakeholders on a provisional 'points to consider' document at various times. Examining in turn the issues of privacy, State powers, stakeholder perceptions, and public participation, we propose in this article, for each of these themes, a series of recommendations aiming to provide guidance on the role of the State in the use of genomic information for public health research, prevention and planning.

The DOSIMAP, a high spatial resolution tissue equivalent 2D dosimeter for LINAC QA and IMRT verification.

The continual need for more accurate and effective techniques in radiation therapy makes it necessary to devise new control means combining high spatial resolution as well as high dose accuracy. Intensity modulated radio therapy (IMRT) allows highly conformed fields with high spatial gradient and therefore requires a precise monitoring of all the multileaf positions. In response to this need, the authors have developed a new 2D tissue equivalent dosimeter with high spatial resolution. A plastic scintillator sheet is sandwiched between two polystyrene blocks and the emitted light is captured by a high resolution camera. A newly developed procedure described herein allows efficient discrimination of the scintillation from the parasitic Cerenkov radiation. This processing is applied on the cumulated image from a sequence of images taken during an irradiation field at a rate of 10 images/s. It provides a high resolution mapping of the cumulated dose in quasireal time. The dosimeter is tissue equivalent (ICRU-44) and works both for electrons and photons without complex parameter adjustment since phantom and detector materials are identical. Instrument calibration is simple and independent of the irradiation conditions (energy, fluence, quality, ...). In this article, the authors present the principle of the dosimeter and its calibration procedure. They compare the results obtained for photons and electron beams with ionization chamber measurements in polystyrene. Technical specifications such as accuracy and repeatability are precisely evaluated and discussed. Finally, they present different IMRT field measurements and compare DOSIMAP measurements to TPS simulations and dosimetric film profiles. The results confirm the excellent spatial resolution of the instrument and its capacity to inspect the leaf positions for each segment of a given field.

Multiple work-related accidents: tracing the role of hearing status and noise exposure.

OBJECTIVES: Our main purpose was to investigate any relationship between noise exposure levels in the workplace, degree of hearing loss (HL), and the relative risk of accident (OR of single or multiple events). METHODS: We conducted a retrospective study of 52 982 male workers aged 16-64 years with long-standing exposures to occupational noise over a 5-year period, using "hearing status" and "noise exposure" from the registry held by the Quebec National Institute of Public Health. Information on work-related accidents was obtained from the Quebec Workers' Compensation Board. Hearing threshold level measurements and noise exposures were regressed on the numbers of accidents after adjusting for age. RESULTS: Exposure to extremely noisy environments (L(eq8h) (equivalent noise level for 8 h exposure) > or =90 dBA) is associated with a higher relative risk of accident. The severity of hearing impairment (average bilateral hearing threshold levels at 3, 4 and 6 kHz) increases the relative risk of single and multiple events when threshold levels exceed 15 dB of hearing loss. The relative risk of multiple events (four or more) is approximately three times higher among severely hearing-impaired workers who are exposed to L(eq8h) > or =90 dBA. CONCLUSION: Single and multiple events are associated with high noise exposure and hearing status. This suggests that reducing noise exposure contributes to increased safety in noisy industries and prevents hearing loss. Hearing-impaired workers assigned to noisy workstations should be provided with assistive listening devices and efficient communication strategies should be implemented.

Ethyl benzene should be considered ototoxic at occupationally relevant exposure concentrations.

Organic solvents can produce ototoxic effects in both man and experimental animals. The objective of this study was to review the literature on the effects of low-level exposure to ethyl benzene on the auditory system and consider its relevance for the occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the permissible exposure limits. In Quebec, the Time-Weighed Average Exposure Value for 8A h (TWAEV) is 100A ppm (434A mg/m(3)) and the Short-Term Exposure Value for 15A min (STEV) is 125A ppm (543A mg/m(3)). In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at STEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. In workers, there is no evidence of either ethyl benzene-induced hearing losses or ototoxic interaction after combined exposure to ethyl benzene and noise. In rats, ethyl benzene affects the auditory function mainly in the cochlear mid-frequency range and ototoxic interaction was observed after combined exposure to noise and ethyl benzene. Further studies with sufficient data on the ethyl benzene exposure of workers are necessary to make a definitive conclusion. Given the current evidence from animal studies, we recommend considering ethyl benzene as an ototoxic agent.

Occupational ototoxicity of n-hexane.

The ability of chemicals to produce hearing loss themselves or to promote noise-induced hearing loss has been reported for some organic solvents. The objective of this study was to review the literature on the effects of low-level exposure to n-hexane on the auditory system and consider its relevance for occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the permissible inhalation exposure limits. In Quebec, the time-weighted average exposure value (TWAEV) for 8 h is 50 ppm. In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at five times the TWAEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. There is no convincing evidence of n-hexane-induced hearing loss in workers. In rats, n-hexane seems to affect auditory function; however, the site of these alterations cannot be determined from the present data. Further studies with sufficient data on the exposure of workers to n-hexane are necessary to make a definitive conclusion. In the interim, we recommend considering n-hexane as a possibly ototoxic agent.

DOSIMAP: a high-resolution 2-D tissue equivalent dosemeter for linac QA and IMRT verification.

New generation of radiation therapy accelerators requires highly accurate dose measurements with high spatial resolution patterns. IMRT is especially demanding since the positioning accuracy of all the multi-leafs should be verified for each applied field and at any incidence. A new 2-D tissue equivalent dosemeter is presented with high spatial resolution that can fulfil these tasks. A plastic scintillator sheet is sandwiched between two polystyrene cubes, and the emitted light is observed by a high-resolution camera. A patented procedure allows efficient discrimination of the scintillation proportional to the dose from the parasitic Cerenkov radiation. This extraction made on the cumulated images taken during an irradiation field at a rate of 10 images s(-1) provides high-resolution mapping of the dose rate and cumulated dose in quasi real time. The dosemeter is tissue equivalent (ICRU-44) and works both for electrons and photons without complex parameter adjustment, since phantom and detector materials are identical. The calibration is simple and independent of the irradiation conditions (energy, fluence, quality and so on). The principle of the dosemeter and its calibration procedure are discussed in this paper. The results and, in particular, the dose depth profiles are compared with standard ionisation chamber measurements in polystyrene for both photons and electrons. Finally, the detector specifications are summarised and one example of complex IMRT field is discussed.

Ototoxicity of trichloroethylene in concentrations relevant for the working environment.

Organic solvents can cause hearing loss themselves or promote noise-induced hearing loss. The objective of this study was to review the literature on the effects of low-level exposure to trichloroethylene on the auditory system and consider its relevance for the occupational settings. Both human and animal investigations were evaluated only for realistic exposure concentrations based on the Quebec permissible exposure limits: 50 ppm 8-h time-weighed average exposure value (TWAEV) and 200 ppm short-term exposure value (STEV). In humans, the upper limit for considering ototoxicity data relevant to the occupational exposure situation was set at the STEV. Animal data were evaluated only for exposure concentrations up to 100 times the TWAEV. There is no convincing evidence of trichloroethylene-induced hearing losses in workers. In rats, trichloroethylene affects the auditory function mainly in the cochlear mid- to high-frequency range with a lowest observed adverse effect level (LOAEL) of 2000 ppm. No studies on ototoxic interaction after combined exposure to noise and trichloroethylene were identified in humans. In rats, supra-additive interaction was reported. Further studies with sufficient data on the trichloroethylene exposure of workers are necessary to make a definitive conclusion. In the interim, we recommend considering trichloroethylene as an ototoxic agent.

The DosiMap, a new 2D scintillating dosimeter for IMRT quality assurance: characterization of two Cerenkov discrimination methods.

New radiation therapy techniques such as IMRT present significant efficiency due to their highly conformal dose distributions. A consequence of the complexity of their dose distributions (high gradients, small irradiation fields, low dose distribution, ...) is the requirement for better precision quality assurance than in classical radiotherapy in order to compare the conformation of the delivered dose with the planned dose distribution and to guarantee the quality of the treatment. Currently this control is mostly performed by matrices of ionization chambers, diode detectors, dosimetric films, portal imaging, or dosimetric gels. Another approach is scintillation dosimetry, which has been developed in the last 15 years mainly through scintillating fiber devices. Despite having many advantages over other methods it is still at an experimental level for routine dosimetry because the Cerenkov radiation produced under irradiation represents an important stem effect. A new 2D water equivalent scintillating dosimeter, the DosiMap, and two different Cerenkov discrimination methods were developed with the collaboration of the Laboratoire de Physique Corpusculaire of Caen, the Comprehensive Cancer Center François Baclesse, and the ELDIM Co., in the frame of the MAESTRO European project. The DosiMap consists of a plastic scintillating sheet placed inside a transparent polystyrene phantom. The light distribution produced under irradiation is recorded by a CCD camera. Our first Cerenkov discrimination technique is subtractive. It uses a chessboard pattern placed in front of the scintillator, which provides a background signal containing only Cerenkov light. Our second discrimination technique is colorimetric. It performs a spectral analysis of the light signal, which allows the unfolding of the Cerenkov radiation and the scintillation. Tests were carried out with our DosiMap prototype and the performances of the two discrimination methods were assessed. The comparison of the dose measurements performed with the DosiMap and with dosimetric films for three different irradiation configurations showed discrepancies smaller than 3.5% for a 2 mm spatial resolution. Two innovative discrimination solutions were demonstrated to separate the scintillation from the Cerenkov radiation. It was also shown that the DosiMap, which is water equivalent, fast, and user friendly, is a very promising tool for radiotherapy quality assurance.

Spectral discrimination of Cerenkov radiation in scintillating dosimeters.

Radiation therapy accelerators require highly accurate dose deposition and the output must be monitored frequently and regularly. Ionization chambers are the primary tool for this control, but their size, their high voltage needed, and the correction needed for electrons make them unsuitable for use during patient treatment. We have developed a small (1-mm-diam and 1-mm-long active part), flexible, and water-equivalent dosimeter. It is suitable for photon and electron beams without corrections, and performs on line dose measurements. This detector is based on only one scintillating fiber and a CCD camera. A new signal processing is used to remove the effect of Cerenkov radiation background, which only requires a preliminary calibration. Central-axis depth-dose distribution comparisons have been achieved with standard ionization chambers, over a range from 8 to 25 MV photons and from 6 to 21 MeV electrons in order to validate this calibration. Results show a very good agreement, with less than 1% difference between the two detectors.

Pregnancy and obstetrical outcomes in pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a genetic multisystem disorder characterized by calcified dystrophic elastic fibres in skin, retina and arteries. Much of the earlier literature on pregnancy in PXE contained reports of severe complications, leading some healthcare providers to advise women with PXE against becoming pregnant and some women with PXE to avoid pregnancy. OBJECTIVES: To evaluate the obstetrical outcomes and the incidence of pregnancy complications in women with PXE and to determine if pregnancy is associated with an adverse effect on the course of the disease. METHODS: Women with PXE (n = 407) answered detailed questionnaires regarding reproductive history and pregnancy as well as the course of their disease. The frequency of reported pregnancy outcomes and complications was determined. Severity indices for the major clinical manifestations of PXE were developed and correlated with gravidity of affected women aged 40 years or over. RESULTS: Among the 306 respondents with PXE who had ever been pregnant, there were 795 pregnancies. Of these, 83% ended in live births and 1% in stillbirth. The median birth weight was within the normal range and the incidence of low birth weight for gestation was low. Hypertension occurred in 10% of pregnancies, gastric bleeding and retinal complications in < 1%, and 12% of pregnancies were associated with worsening of skin manifestations. There was no effect of gravidity and clinical severity on cutaneous (P = 0.07), ocular (P = 0.59) or cardiac (P = 0.42) manifestations of PXE in women aged 40+ years, nor did ever having been pregnant adversely affect these clinical severity indices. Of the 101 women who had never been pregnant, 17% made the decision because they were advised against becoming pregnant by a healthcare professional and 11% did not become pregnant because they feared an adverse outcome either in their pregnancy or disease. CONCLUSIONS: PXE is not associated with markedly increased fetal loss or adverse reproductive outcomes. The incidence of gastric bleeding, although probably higher than in the unaffected population, is much lower than previously reported, and retinal complications are uncommon. Although a few pregnancies were associated with worsening of skin manifestations, there was no correlation of either gravidity or ever having been pregnant with ultimate severity of skin, ocular or cardiovascular manifestations. There is no basis for advising women with PXE to avoid becoming pregnant, and most pregnancies in PXE are uncomplicated.

Reaching homeless youths for Chlamydia trachomatis and Neisseria gonorrhoeae screening in Denver, Colorado.

BACKGROUND AND RATIONALE: The availability of urine based testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) provides a unique opportunity to screen for these pathogens outside traditional clinical settings. The researchers investigated the feasibility of street based CT/GC screening in the context of an outreach programme among street/homeless adolescents in Denver. OBJECTIVES: To describe the integration of urine based CT/GC screening into an existing outreach programme among street/homeless youths and the yield of CT/GC testing in this setting. METHODS: The Denver Department of Public Health (DPH) collaborated with outreach staff from Urban Peak (a community based organisation serving street/homeless youths in Denver) to offer urine based CT/GC testing to males and females in street settings. Tests were conducted on the street in areas where street/homeless youths congregate. RESULTS: Urban Peak outreach staff were trained by DPH staff to conduct CT testing, process urine specimens, and provide test results to participating youths. DPH remained responsible for treatment of people with CT or GC infection as well as CT/GC case reporting. CT testing started in January 2000; GC testing was added in July 2000. Throughout April 2002 a total of 414 CT and 302 GC tests were conducted, respectively 11.6% and 2.7% of which were positive. Among first testers, 13.0% were positive for CT and 3.7% for GC. CONCLUSIONS: CT/GC urine testing can be incorporated into existing outreach programmes without considerable extra effort. Overall CT rates were high and suggest the need for ongoing screening in this manner. LEARNING OBJECTIVE: To understand the role of CT/GC screening in the context of services provided to street/homeless youths in outreach settings.

High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria.

There is accumulating evidence for a role of immunoglobulin G (IgG) in protection against malarial infection and disease. Only IgG1 and IgG3 are considered cytophilic and protective against P. falciparum, whereas IgG2 and IgG4 were thought to be neither and even to block protective mechanisms. However, no clear pattern of association between isotypes and protection has so far emerged. We analyzed the isotypic distribution of the IgG response to conserved epitopes and P. falciparum blood-stage extract in 283 malaria-exposed individuals whose occurrence of infection and malaria attack had been monitored for about 1 year. Logistic regression analyses showed that, at the end of the season of transmission, high levels of IgG2 to RESA and to MSP2 epitopes were associated with low risk of infection. Indeed, IgG2 is able to bind FcgammaRIIA in individuals possessing the H131 allele, and we showed that 70% of the study subjects had this allele. Also, high specific IgG4 levels were associated with an enhanced risk of infection and with a high risk of malaria attack. Moreover, specific IgG2 and IgG3 levels, as well as the IgG2/IgG4 and IgG3/IgG4 ratios, increased with the age of subjects, in parallel with the protection against infection and disease. IgG4 likely competes with cytophilic antibodies for antigen recognition and may therefore block cytotoxicity mediated by antibody-activated effector cells. In conclusion, these results favor a protective role of IgG3 and IgG2, which may activate effector cells through FcgammaRIIA, and provide evidence for a blocking role of IgG4 in malarial infection and disease.