Traditional methods of measuring oral health mainly use clinical dental indices and have been complemented by oral health related quality of life (OHRQoL) measures. Most OHRQoL studies have been on adults and elderly populations. There are no systematic OHRQoL studies of a population-based sample of children. The objective of this study was to assess the prevalence, characteristics and severity of oral impacts in primary school children.Cross-sectional study of all 1126 children aged 11–12 years in a municipal area of Suphanburi province, Thailand. An OHRQoL measure, Child-Oral Impacts on Daily Performances index (Child-OIDP) was used to assess oral impacts. Children were also clinically examined and completed a self-administered questionnaire about demographic information and oral behaviours.89.8% of children had one or more oral impacts. The median impact score was 7.6 and mean score was 8.8. Nearly half (47.0%) of the children with impacts had impacts at very little or little levels of intensity. Most (84.8%) of those with impacts had 1–4 daily performances affected (out of 8 performances). Eating was the most common performance affected (72.9%). The severity of impacts was high for eating and smiling and low for study and social contact performances. The main clinical causes of impacts were sensitive tooth (27.9%), oral ulcers (25.8%), toothache (25.1%) and an exfoliating primary tooth (23.4%).The study reveals that oral health impacts on quality of life in Thai primary school children. Oral impacts were prevalent, but not severe. The impacts mainly related to difficulty eating and smiling. Toothache, oral ulcers and natural processes contributed largely to the incidence of oral impacts. Contemporary concepts of health suggest that dental health should be defined in physical, psychological and social well-being terms in relation to dental status ,2. That A number of socio-dental or OHRQoL measures have been developed and used for assessing oral well-being and to describe oral impacts on people's quality of life . GeneralMost studies using OHRQoL to assess oral impacts of the mouth and teeth have been on adults and elderly populations. Few studies have been done on children possibly because no OHRQoL measures designed for use with children existed until recently. A single measure, dental pain, has been used on children in Malaysia  and in SA cross-sectional survey was carried out in a municipal area of Muang district, Suphanburi province, Thailand. The sample was all 1,126 students aged 11–12 years, in the final year class of all primary schools (grade 6) in the area.Data were collected through: a) an interview for oral impacts using the Child-OIDP , by one The protocol of the study was approved by the Ethical Committee of the Ministry of Public Health of Thailand. Primary education and local health authorities as well as all primary schools in the study areas gave permission. Positive consent forms and letters informing parents were sent to parents.Two comprehensive OHRQoL measures specifically for use with pre-adolescent children have recently been developed; the Child Perceptions Questionnaire (CPQ11-14)  and the The procedure for using the Child-OIDP began with a self-administered questionnaire carried out with all children as a group in their classroom. The questionnaire contains a list of all oral problems that children are likely to perceive and also include an open answer for any unexpected perceived problem. It was developed during a pilot study, as a modification from the one used in the original OIDP. Children were asked to identify oral problems that they perceived in the last three months. This step aimed to focus children's attention to their oral health problems and to lead to the oral impacts assessment later. Their answers here were used only as a guide to investigate oral impacts on daily performances in the next step and were referred to when they were asked about the causes of oral impacts in individual interviews. Thereafter, children were individually interviewed, irrespective of their answers at the first step, to assess oral impacts on daily life in relation to 8 daily performances. The 8 performances were: a) eating, b) speaking, c) cleaning teeth, d) relaxing, including sleeping, e) smiling, laughing and showing teeth without embarrassment, f) maintaining emotional state, g) study, including going to school and doing homework and h) contact with other people. The individual interviews were aided by 16 pictures (negative and positive pictures for each performance). If children reported an impact on any performance, the frequency of the impact and the severity of its effect on their daily life were scored. Children were also asked to identify oral problems that in their opinion, caused the impact. The oral problems were identified from the list complied in the first step of the assessment.The oral impact score of each performance is obtained by multiplying severity and frequency scores, 0, 1, 2 or 3 each, in relation to that performance. Therefore scores can range from 0 to 9 per performance. The overall impacts score is the sum of all 8 performances (ranging from 0 to 72) divided by 72 and multiplied by 100. An alternative method of reporting the severity of oral impacts, from the same data set, is to use the 'intensity' and 'extent' of impacts. The intensity refers to the most severe impacts on any of the 8 performances or the highest performance score. It is classified into 6 levels; none, very little, little, moderate, severe and very severe  completed all stages of the survey. 52.4% were male and 47.6% were female. Their mean age was 11.3 years (sd = 0.6). The highest percentage of their fathers were agricultural workers or labourers (34.5%), 30.5% worked in business/private, 27.5% in governmental sectors, 2.1% did not work and 5.4% of children did not have a male guardian. The highest percentage of mothers worked in business/private (38.6%), 24.5% in agriculture, 21.1% in governmental organisations. 14.9% did not work and 1.0% did not have a female guardian.This population had a low level of dental caries: 43.1% were caries free and the DMFT scores ranged from 0 to 12 with a median score of 1.0 and a mean of 1.5 (±1.8). Almost all children (97.0%) had a Community Periodontal Index (CPI) score of 1 or more; 84.2% had calculus. In terms of oral hygiene status, 5.4% had good, 69.1% had moderate and 25.5% had poor oral hygiene. OHI-S scores ranged from 0.5–5.5 with a median of 2.5 and mean score of 2.5 (±0.9), indicating a moderate level of oral hygiene.The prevalence of oral impacts was high; 89.8% of children had experienced some kind of oral impact on their daily life during the past three months. There was no difference between the prevalence of impacts in girls and boys (Chi-square test). Impacts on Eating were the most prevalent 72.9%). The prevalence of impacts on Emotion (58.1%), Cleaning teeth (48.5%) and Smiling (40.1%) were also relatively high. The remaining prevalences of impacts were lower, namely Study (15.4%), Relaxing (14.7%), Contact with people (12.2%) and Speaking (9.9%) ; 16.2% had 1 PWI, 23.3% had 2, 26.9% had 3 and 18.4% had 4 PWIs. Few children had 5 or more PWIs. About 1 in 5 children had severe or very severe intensity of impacts; 18.7% had severe and 2.6% had very severe intensity of impacts.15.9% had very little, 31.1% had little and 31.7% had moderate intensity of impacts . This is surprising in that this was a low caries population in an area with a free accessible school dental service. Although there is no study using OHRQoL index with a population-based sample of 12 year olds to compare with, findings of previous OHRQoL studies suggest that oral impacts are very common in children of this age. In Brazilian adolescent populations, the prevalence of impacts was 32% ,20 and 69.8%. ThiDespite the fact that oral impacts were prevalent in this Thai child population, they were not severe. For example, half of this population had Child-OIDP score less than 7.6 and half of those with impacts had very little or little intensity of impacts Table . MoreoveThis study found that eating was the most important aspect of OHRQoL of children. Difficulty with eating due to oral problems was the most common impact (72.9%), and led to more severe oral impacts on children's quality of life than impacts on other performances. Oral ulcers and exfoliating primary teeth contributed to eating difficulties in nearly half of those with impacts. The finding that eating was the most common performance affected is similar to all studies using the OIDP in all age groups ,21-24. TDifficulty with smiling was another important aspect of children's OHRQoL. It affected 40% of children. The most prevalent cause was position of teeth. Dissatisfaction with position of teeth, moreover, accounted for oral impacts in 1 in 5 of all children Table . AlthougGum problems were the other important oral conditions affecting children's OHRQoL. More than one fifth of children perceived that bleeding and swollen gums caused oral impacts on their life, particularly in relation to difficulty cleaning, a problem experienced by nearly half of all children Table . ChildreAn interesting finding was that impacts relating to social dimensions, such as study being affected and contact with people, were less common and least severe. Schor suggested that children's social performances rely more on their physical and psychological performances than adults .It is apparent that an important reason for the high prevalence of oral impacts in children is natural processes such as exfoliating primary teeth or spaces due to a non-erupted permanent tooth. They contributed largely to the high incidence of impacts in these pre-adolescent children. On the other hand, these conditions were not reported as important causes of oral impacts in other age groups ,22. The Although children could often not specify precisely which impairments led to impacts, the question of perceived clinical causes should exclude impacts from some conditions which are definitely not related to actual impairments as well as to treatment needs. For example, toothache, ulcers and conditions relating to appearance definitely require different treatment and could be easily differentiated. However, the accuracy of detecting perceived impairment is limited in a population-based study, while it can be improved at the individual level of investigation.The specific age group under investigation, particularly in relation to their stage of development, may have influenced the high prevalence of oral impacts. Developmental changes unavoidably affect HRQoL between childhood and adolescence . MaturitThe prevalence of oral impacts on daily performances in this child population was very high. Oral impacts affected children's quality of life mainly through difficulty eating and smiling. There are various oral conditions that contributed significantly to the incidence of impacts, namely, sensitive teeth, toothache, oral ulcers and exfoliating primary teeth. Although the prevalence of impacts was high, the severity was not; many children had their quality of life affected at low levels. This reveals a need for further longitudinal studies to better understand and interpret OHRQoL measures in children.SG carried out all work including data collection, data analysis and writing the paper. GT supervised the project and assisted writing. AS initiated the idea of, and supervised the project and edited writing.


Human tooth pulp was extracted from teeth harvested from a total of twenty-two patients .Using specific antibodies for immunohistochemistry, we studied Nav1.8, were significantly increased on image analysis in the painful group: median (range) Nav1.8 to Neurofilament % area ratio, non-painful 0.059 (0.006–0.24), painful 0.265 (0.13–0.5), P = 0.0019.Fibres immunoreactive for Nav1.8 sodium channels may thus represent a therapeutic target in trigeminal nerve pain states.Na Pain is the most common symptom of diseased tooth pulp, often a result of coronal caries of the tooth, affecting up to 80% of the western population during their lives. The mature human dental pulp is densely innervated with over 900 axons entering the average human premolar tooth  that oriv1.8, (SNS/PN3) have been the focus of research in pain mechanisms [v1.8 in human sensory neurones [v1.8 in predominantly small medium sized neurons in human DRG, it is likely that Nav1.8 is present in both A delta and C fibres [Voltage-gated sodium channels play key roles in the pathophysiology of pain and are distinguished according to their sensitivity to the neurotoxin tetrodotoxin (TTX) as fast-activating TTX-sensitive (TTX-S) channels, or slow-inactivating TTX-resistant channels (TTX-R). The distribution and pathophysiology of these channels, particularly Nachanisms . Recentlneurones ; the chaC fibres ,10.v1.8-immunoreactivity within tooth pulp nerve fibres.This study aimed to assess if pulpal pain associated with caries was associated with any change of NaPatients scheduled for dental extraction at Guy's Dental Institute, London, were included in the study, subsequent to providing consent in accordance with the local research ethics committee.22 permanent molar teeth about to be extracted were tested, 1 hour prior to extraction, for vitality using an electric pulp tester  and with ethyl chloride to confirm the neural vitality of the dental pulp. A pain history was also collected (existing pain and duration). The patients were divided into two groups, those with existing pain from the tooth (n = 8 patients age range: 40.3 ± 4.0 years) and those with no history of or existing pain (n = 14 patient age range: 37.3 ± 14.6 years). The gender distribution of the groups was M:F 1:1. All the dental pain in this study was attributable to pulpitis due to extensive dental caries of the molar tooth, the duration of pain was 2.9 weeks (range 0.5–8), and the indication for extraction of the non-painful teeth was pericoronitis. All the teeth were removed by standard buccal approach under local or general anaesthesia. Subsequent to the extraction process (lasting less than 5 min), the teeth were sectioned vertically with a water-cooled drill and the pulp lifted out, and specimens immediately snap-frozen at -70°C. Intentional examination of the coronal pulp, including the densely innervated subontoblastic layer, was assisted by careful orientation of the pulp on a marked sterile card. Based on the number of inflammatory cells present, the inflammation was graded in accordance with local histological standard scales, which were mild, moderate or severe.v1.8 (K107), whose specificity has been described by us previously [v1.8 antibody (K107), showing positive staining in human DRG neurons, and no staining in pre-absorption experiments using Nav1.8 peptide in tooth pulp sections, were performed as previously described [Frozen pulp or nerve were embedded in OCT medium  and sections of 12 μm thaw-mounted onto glass slides pre-coated with poly-L-lysine. Sections were immersion-fixed in fresh 4% paraformaldehyde in phosphate buffered saline (PBS) for 30 min, then endogenous peroxidases blocked by incubation with alcoholic 0.3% hydrogen peroxide for a further 30 min. Sections were incubated overnight with a monoclonal antibody to the neuronal marker neurofilament  and a polyclonal antibody against the Naeviously . Sites oescribed .v1.8 and neurofilament immunoreactivity in fibres were quantified using computerized image analysis . Quantification of the data was performed using 12-micron thick serial sections. Images were captured via video link to an Olympus BX50 microscope  and scanned by computer. Setting grey-level detection limits at threshold, highlighted positive immunostaining, and the area of highlighted fibres was obtained as % area of the field scanned. Scanning was performed for a minimum of 5 fields at random per tissue section orientated longitudinally, assessed in a blind fashion; 3 tissue sections from each pulp were analysed, and the mean value from each patient obtained. Results are expressed as the average percentage ratio of the mean Nav1.8 to neurofilament reactive fibres in 5 fields.NaP values less than 0.05 were considered significant.The Mann Whitney test was used to compare ratios between groups; v1.8 antibody  compared to painful tooth pulp 5.855 (1.3–7.52), P < 0.005. There were also significantly more fibres immunostaining for Nav1.8 in relationship to neurofilament positive fibres in the painful pulp, compared with those without pain , and for painful 0.265 (0.13–0.5), P < 0.005. A degree of inflammation was seen in all painful pulp samples.By image analysis, neurofilament fibre median % area (range) in non-painful tooth pulp was 13.94 (3.05–22.05), and in painful tooth pulp was 18.21 (9.11–27.88); there was trend for an increase, but this was not statistically significant. There was a significant change of the corresponding Nav1.8-immunoreactive nerve fibres are present in human dental pulp in the subodontoblastic layer, and the Nav1.8-immunoreactive fibres were increased in the presence of caries-induced painful pulpitis. While there was a trend for increased neurofilament fibres in painful dental pulp, this was not statistically significant. An increase of nerve fibres within inflamed dental pulp, possibly due to nerve sprouting, has been previously reported in the rat dental pulp after dentine injury [v1.8 in this study, our previous study of TRPV1 and P2X3 receptors showed no significant change in painful dental human dental pulp [Neurofilament positive fibres have previously been reported in human dental pulp, including fine unmyelinated fibres in the sub odontoblastic layer ,12. Howee injury , and othe injury ,15. In ctal pulp .v1.8-immunoreactive neurons identified in the subodontoblastic layer implies that these receptors may be involved in signal transduction at the pulp-dentine junction. It is known that sensory neurones and odontoblasts exist in close proximity, but no synaptic or electrical connections have been identified [v1.8 expression by sensory neurons [v1.8-immunoreactivity varies with eruption or maturity of teeth.The presence of Naentified ,12 postu neurons ; NGF is  neurons . The samv1.8-immunoreactivity associated with the nodes of Ranvier in the radicular human tooth pulp. The difference in localisation between the studies could reflect characteristics of the antibodies and immunostaining methods, and further studies, including different techniques and functional assays, are necessary. The relative expression of Nav1.8-immunoreactive fibres to neurofilament positive fibres is low – this may also be due to the affinity of the antibody used in this study, or reflect the expression of this ion channel in a small sub-set of nerve fibres. The specific type of fibre expressing Nav1.8, the distribution of Nav1.8 throughout the human dental pulp, and the longitudinal changes in the Nav1.8-immunoreactivity caused by pulpal inflammation, all require further study.Although our cross reactivity and pre-absorption studies showed specificity of the antibodies used, the data should be interpreted with caution. Immunostaining of nerves appears to be axoplasmic in this study, and not at the nodes of Ranvier. Recently  Henry anv1.8-fibres as a proportion of neurofilament positive fibres. As Nav1.8 has been implicated in neuropathic pain, its expression by nerve fibres within human tooth pulp may contribute to the pathophysiology of dental pain. Further studies of the time-course of the disease, and severity of pain and/or inflammation, are necessary to elucidate the role and regulation of Nav1.8 ion channels in the pathophysiology of trigeminal pain. Nav1.8 represents a target for novel analgesic agents.In conclusion, nerve fibres in dental pulp from patients with dental pain showed significantly more NaThe author(s) declare that they have no competing interests.V1.8 antibodies used, help with interpretation of the data, and writing the manuscript. CB participated in the conception of the study, development of antibodies, and interpreting the data. PA conceived the study and participated in its design and coordination, interpretation and completion of the manuscript. All authors read and approved the manuscript.TR performed all the surgical procedures, extracted the tooth pulp and helped write the paper. YY participated in the immunohistochemistry, analysis of data and drafted the manuscript. CP, ST and CB were responsible for the design and production of the NaThe pre-publication history for this paper can be accessed here:


The evolutionary success of mammals is owed in part to their ability to adjust their metabolism to the demands of their environment. For instance, mice faced with dropping external temperatures crank up the output of a specialized type of fat—called brown adipose tissue (BAT) —that generates heat. Faced with a lack of food, they turn on the production of glucose, a highly energetic sugar, by the liver. Both of these adaptive responses depend on a nuclear protein called PGC-1α. PGC-1α simultaneously increases the expression of genes acting at multiple steps along the heat- or glucose-production pathways, thereby quickly boosting the pathways’ efficacy. A related protein, PGC-1β, shares many of PGC-1α’s functional characteristics: for instance, both proteins can, when overexpressed in mice, increase the activity of mitochondria, the intracellular organelles that turn sugars and fats into heat or the cellular fuel ATP. To determine what role PGC-1β normally plays in energy metabolism, Christopher Lelliott, Gema Medina-Gomez, Antonio Vidal-Puig, and their colleagues created mice lacking the PGC-1β gene. Their recent study of the resulting phenotype shows that PGC-1β has different functions than PGC-1α and plays a subtler role than PGC-1α in energy metabolism.As expected from PGC-1β’s ability to stimulate mitochondrial function, the loss of PGC-1β decreased the transcription of genes encoding many of the mitochondrial proteins that generate ATP and heat. Yet the mutant mice appeared essentially healthy under normal conditions. Still, a slight impairment of mitochondrial function might lead to some metabolic imbalance, for instance obesity, since mitochondria burn energy that would otherwise be stored as fat. But the mutant mice were in fact smaller and leaner than their wild-type counterparts. This phenotype did not reflect differences in appetite or digestion, since the mutants ate and eliminated similar amounts of food as wild types. Instead, the mutants had higher metabolic rates than wild types at ambient temperature: they burnt more calories than wild types did to sustain basal physiological functions such as respiration, heartbeat, and body temperature, which would suggest that their mitochondrial functions were increased, rather than decreased.The explanation for these counterintuitive findings is that loss of PGC-1β led to increased expression of PGC-1α in fat tissues. The researchers propose that the increase in PGC-1α, which can stimulate heat production in BAT, compensates for the loss of PGC-1β at ambient temperature. To remove the compensatory effect of PGC-1α, the researchers measured the metabolic rate of mutants housed at 30 °C, a temperature close to body temperature, at which PGC-1α expression is largely abolished. At this temperature, mice lacking PGC-1β had a reduced metabolic rate, suggesting that PGC-1β can contribute to maintaining normal metabolic rates.The mutant mice were able to withstand and adapt to cold, presumably because cold temperatures could still trigger PGC-1α expression. However, when mutant mice that were acclimatized to 4 °C were further stimulated by norepinephrine, a neurotransmitter that normally induces BAT to respond to cold, their BAT heat output was blunted compared to that of wild-type BAT. Therefore, PGC-1β must normally play a role in thermal regulation, though its role is obscured by PGC-1α’s induction at low temperatures.In other tissues such as liver, muscle, and heart, loss of PGC-1β did not trigger PGC-1α expression, which made the role of PGC-1β easier to discern. In the liver, PGC-1β proved necessary for the proper disposal of cholesterol and other lipid forms when mice were fed a diet rich in saturated fat. In muscles and heart, PGC-1β was found necessary to maintain a normal number of mitochondria. But even with a reduced mitochondrial count, the hearts of mice lacking PGC-1β functioned normally. Their only anomaly was a failure to increase their pulse rate properly when challenged with the heart stimulant dobutamine. By comparison, mice lacking PGC-1α develop severe heart failure.These observations show that although PGC-1β and PGC-1α share sequence and functional similarities and are expressed in the same tissues, they cannot completely substitute for one another. The researchers propose that PGC-1β maintains basal metabolic functions, whereas PGC-1α allows the body to step up it response to high energetic demands.


In 1993, the Intelligent Systems for Molecular Biology conference was successfully launched as an annual meeting for scientific exchange within the nascent interdisciplinary science of computational biology. Demand grew stronger each year for an umbrella organization that extended its reach beyond a once-a-year conference. The International Society for Computational Biology (ISCB) was formed in 1997 to provide computational biologists and bioinformaticians worldwide with a community of peers with whom they could interact year-round in their mutual quest to advance the understanding of living systems through computation. Over the past 13 years, the ISCB has grown and evolved along with the fields of computational biology and bioinformatics. As the society's president, I am proud to report that our membership now comprises nearly 2,000 members in over 50 countries.PLoS Computational Biology, as the official journal of the ISCB, will publish the bylaws of the society. These are the legally registered rules by which the elected and appointed leaders of the society, along with the membership at large, must abide. It is my hope that ISCB members will take the time to read these rules, and to understand, thereby, the legal framework in which ISCB operates. Clearly, as ISCB grows, these rules will be adapted to changing circumstances—knowing the current rules is a first step to making any improvements to them. We also believe that our bylaws may be useful to other groups trying to form similar organizations.Each year, The principal office of the Corporation shall be at San Diego Supercomputer Center, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0505The Corporation may also have an office or offices in such other place or places as the business of the Corporation may require and the Board of Directors may from time to time appoint.The annual meeting of the members of the Corporation shall be held on a day duly designated by the Board of Directors either within or without the United States if not a legal holiday, and if a legal holiday then the next succeeding day not a legal holiday, for the transaction of such corporate business as may come before the meeting.Special meetings of the members may be called at any time for any purpose or purposes by the Chairman of the Board, the President, a Vice President, or a majority of the Board of Directors, and shall be called forthwith by the Chairman of the Board, the President, a Vice President, the Secretary or any Director of the Corporation upon the request in writing of a majority of all the members entitled to vote on the business to be transacted at such meeting. Such request shall state the purpose or purposes of the meeting. Business transacted at all special meetings of members shall be confined to the purpose or purposes stated in the notice of the meeting.All meetings of members shall be held within or without the United States at a place designated by the Board of Directors. The members may hold their meetings in person, by conference telephone, by E-mail over the Internet or other similar electronic media, or by any combination of the foregoing.Written notice of each meeting of the members shall be mailed, postage prepaid by the Secretary or person appointed by the President or sent by E-mail over the Internet or similar electronic media by the Secretary or person appointed by the President, to each member of record entitled to vote thereat at his or her post office address or E-mail address, as it appears upon the books of the Corporation, at least ten (10) days before the meeting. Each such notice shall state the place, E-mail information if the meeting will be held partly or completely by electronic means over the Internet or other electronic media, day, and hour at which the meeting is to be held and, in the case of any special meeting, shall state briefly the purpose or purposes thereof.The presence in person, by E-mail over the Internet or similar electronic media, or by proxy , of one third of the members of the Corporation shall constitute a quorum at all meetings of the members except as otherwise provided by law, by the Certificate of Incorporation or by these bylaws If less than a quorum shall be in Attendance at the time for which the meeting shall have been called, the meeting may be adjourned from time to time by a majority vote of the members in Attendance, without any notice other than by announcement at the meeting, until a quorum shall be in Attendance. At any adjourned meeting at which a quorum shall be in Attendance, any business may be transacted which might have been transacted if the meeting had been held as originally called.Meetings of members shall be presided over by the President of the Corporation or, if he is not in Attendance, by a Vice President, or, if none of said officers is in Attendance, by a chairman to be elected at the meeting. The Secretary of the Corporation, or if he is not in Attendance, any Assistant Secretary shall act as secretary of such meetings; in the absence of the Secretary and any Assistant Secretary, the presiding officer may appoint a person to act as Secretary of the meeting.At all meetings of members every member entitled to vote thereat shall have one (1) vote. Such vote may be made either in person, by conference call, by E-mail over the Internet or similar electronic media, or by proxy appointed by an instrument in writing subscribed by such member or his or her duly authorized attorney, bearing a date not more than three (3) months prior to said meeting, unless said instrument provides for a longer period. Such proxy shall be dated, but need not be sealed, witnessed or acknowledged. All elections shall be had and all questions shall be decided by a majority of the votes cast at a duly constituted meeting, except as otherwise provided by law, in the Certificate of Incorporation or by these bylaws.If the chairman of the meeting shall so determine, a vote by ballot may be taken upon any election or matter, and the vote shall be so taken upon the request of ten percent (10%) or more of all of the members entitled to vote on such election or matter. In either of such events, the proxies and ballots shall be received and be taken in charge and all questions touching the qualification of voters and the validity of proxies and the acceptance or rejection of votes, shall be decided by members appointed by the chairman of said meeting.The members of the Corporation shall be composed of those individuals who have filled out a registration form and paid their dues. Individuals shall retain their status as members so long as they pay any and all annual dues imposed by the Corporation upon its members.The members of the Corporation shall nominate from the membership, no later than their annual meeting in the manner set forth in the Procedure for Nomination, up to four (4) Directors who shall also be concurrently nominated to hold one of the Nominated Offices as further defined in Article IV, Section 1 below. Said nominations shall be considered strong recommendations from the members to the Board of Directors to elect these individuals as officers and Directors of the Corporation (the “Director/Officers”). Upon their election by the Directors as set forth in Article III, Section 4 below, these four Director/Officers shall serve as officers of the Corporation for one year in the case of President-elect, and two years for all other officers including President. The four Director/Officers shall also concurrently serve as Directors of the Corporation during their full term as officers plus one year following completion of their term or terms of office, unless removed by the Directors pursuant to the provisions of Article III, Section 4(iv) below. The membership shall follow such rules pertaining to the nomination of officers as are promulgated by the Board of Directors in the Procedure For Nomination adopted as of March 2003 as attached to these bylaws as Exhibit A, or as later amended.The Board of Directors of the Corporation shall be members. A Director who fails to keep his or her membership current during the course of his or her term will forfeit voting rights until current year registration is rectified, or resign from the Board of Directors if not registered by April 1 of the membership year.The property and business of the Corporation shall be managed under the direction of the Board of Directors of the Corporation.The number of Directors, including Director/Officers, shall be twenty eight (28) or such other number, but not less than three (3) nor more than thirty (30), as may be designated from time to time by resolution of a majority of the entire Board of Directors.The term of office of each Director, other than a Director/Officer, shall be for three (3) years; the term of office of each Director/Officer shall be for the duration of the term or terms of office of the officer plus one additional year after the final term as officer.In the case of any vacancy in the Board of Directors, including Director/Officers, the remaining Directors may elect a successor at a regular or special meeting of Directors, by affirmative vote of the majority thereof.In the case of any vacancy in the Director/Officers, the Directors may, but are not required to, ask the members to make nominations under the Procedure for Nomination.If the number of Directors is increased as provided in these bylaws, the additional Directors so provided for shall be elected by an affirmative vote of a majority of the entire Board of Directors already in office to hold office for a three (3) year term.Notwithstanding the foregoing provisions, any Director, including a Director/Officer, may be removed from office as a Director with or without cause by the affirmative vote of a majority of the Directors entitled to vote at any regular or special meeting of Directors called for that purpose. A Director who is a Director/Officer shall be automatically removed as an officer of the Corporation upon his or her removal as a Director.The Board of Directors may hold their meetings and have one or more offices, and keep the books of the Corporation, either within or outside the State of California, at such place or places as they may from time to time determine by resolution or by written consent of all the Directors. The Board of Directors may hold their meetings in person, by conference telephone, by E-mail over the Internet or other similar electronic media, or by any combination of the foregoing.Regular meetings of the Board of Directors may be held at such time and place as shall from time to time be determined by resolution of the Board, provided that written notice of each meeting of the Board of Directors shall be mailed, postage prepaid by the Secretary or person appointed by the President or sent by E-mail over the Internet or similar electronic media by the Secretary or person appointed by the President, to each Director and Director/Officer at his or her post office address or E-mail address, as it appears upon the books of the Corporation, at least ten (10) days before the meeting. The annual meeting of the Board of Directors shall be held within ten days prior to or following the annual meeting of members. Any business may be transacted at any regular meeting of the Board.Special meetings of the Board of Directors shall be held whenever called by any member of the Board of Directors. The Secretary or person appointed by the President shall give notice of each special meeting of the Board of Directors, by mailing the same at least three (3) days prior to the meeting or by E-mailing over the Internet or similar electronic media, the same at least two (2) days before the meeting, to each Director; but such notice may be waived by any Director. Unless otherwise indicated in the notice thereof, any and all business may be transacted at any special meetings. At any meeting at which every Director shall be in Attendance, even though without notice, any business may be transacted and any Director may in writing or by E-mail over the Internet or similar electronic media, waive notice of the time, place and objectives of any special meeting.The presence in person, by conference call, by E-mail over the Internet or similar electronic media, or by proxy appointed by an instrument in writing subscribed by such Director or his or her duly authorized attorney, bearing a date not more than three (3) months prior to said meeting, unless said instrument provides for a longer period   of a majority of the whole number of Directors shall constitute a quorum for the transaction of business at all meetings of the Board of Directors. If at any meeting less than a quorum shall be in Attendance, a majority of those in Attendance may adjourn the meeting from time to time. The act of a majority of the Directors in Attendance at any meeting at which there is a quorum shall be the act of the Board of Directors, except as may be otherwise specifically provided by law, by the Certificate of Incorporation or by these bylaws.An affirmative vote of a majority of those in Attendance shall be necessary for the passage of any resolution.Directors, including Director/Officers, shall not receive any stated salary for their services as such, but, at the discretion and unanimous approval by the Executive Committee, a fixed sum may be allowed for Attendance at each regular or special meeting of the Board and such compensation shall be payable whether or not a meeting is adjourned because of the absence of a quorum. This sum may be disbursed to all Directors, including Director/Officers, or to individual Directors or Director/Officers with extenuating circumstances regarding lack of institutional reimbursement of costs for Attendance at each regular or special meeting. If the sum to any or all of the Directors and Director/Officers exceeds $5000, it must be approved by majority vote of the Board. Nothing herein contained shall be construed to preclude any Director or Director/Officer from serving the Corporation in any other capacity, and receiving compensation therefore.The Board of Directors shall elect a septe Standing Committee for the conference coordination for the annual ISMB meeting which is responsible for oversight of all ISCB conference activities sponsored by and affiliated with the Corporation. Another Standing Committee shall be elected to assume responsibility for publications of the society. A Task Force shall be selected for the election of officers and for the setting of standards for voting at meetings held on the Internet or by other electronic media and shall consist of such Directors and members as determined by majority vote of the Directors. The Standing Committees shall be selected by the Board of Directors at any meeting of the Board of Directors. Any and all Task Forces may be selected by the Board of Directors at any duly constituted meeting of the Directors or by the Committee Chair(s) at any committee meeting.The Board of Directors may, by resolution passed by a majority of the whole Board, designate one or more other committees, each committee to consist of one or more of the Directors of the Corporation, which, to the extent provided in the resolution, shall have and may exercise the powers of the Board of Directors, and may authorize the seal of the Corporation to be affixed to all papers which may require it. Such committee or committees shall have such names as may be determined from time to time by resolution adopted by the Board of Directors.The Board of Directors and committee chairs may, by resolution passed by a majority of the whole Board or at the direction of the committee chairs, designate one or more Task Forces, each Task Force to consist of one or more of the Directors of the Corporation or one or more of the committee members for which the Task Force shall be formed. Task Forces shall be formed for the purposes of task-specific time-limited work in order to make recommendations to the Board of Directors or committee chairs. Task Forces shall not have nor exercise the powers of the Board of Directors, nor authorize the seal of the Corporation to be affixed to any papers which may require it. Such Task Forces shall have such names as may be determined from time to time by resolution adopted by the Board of Directors or at the direction of the committee chairs for which they have formed.The officers of the Corporation shall be a President-elect, a President, a Vice President, a Secretary, and a Treasurer (the “Nominated Officers”), and also such other officers including a Chairman of the Board and/or one or more Vice Presidents and/or one or more assistants to the foregoing officers as the Board of Directors from time to time may appoint for the proper conduct of the business of the Corporation, including but not limited to an Executive Officer to assist in day to day business matters and a Vice Chair of Conferences to assist in managing the annual conference (collectively the “Appointed Officers”). The Nominated Officers shall be nominated by the members and Directors according to the procedures set forth in the Procedure For Nomination. The Nominated Officers shall serve for two years as officers. Any two or more of the above offices, except those of President and Secretary, may be held by the same person, but no officer shall execute, acknowledge or verify any instrument in more than one capacity if such instrument is required by law or by these bylaws to be executed, acknowledged or verified by any two or more officers. If compensation or salary is paid to officers or Director/Officers of the Corporation it shall be fixed by resolutions adopted by the Board of Directors.In the event that any office other than an office required by law, shall not be filled by the members, or, once filled, subsequently becomes vacant, then such office and all references thereto in these bylaws shall be deemed inoperative unless and until such office is filled in accordance with the provisions of these bylaws.Except where otherwise expressly provided in a contract duly authorized by the Board of Directors, all officers of the Corporation shall be subject to removal at any time by the affirmative vote of a majority of the Board of Directors or the whole membership at a special meeting of the Board of Directors or the members respectively, duly called according to the rules set forth in these bylaws. All agents and employees of the Corporation shall be subject to removal at any time by the affirmative vote of a majority of the whole Board of Directors, and any agents and employees, other than those elected by the membership, shall hold office at the discretion of the Board of Directors or of the officers appointing them.The Chairman of the Board shall preside at all meetings of the Board of Directors unless the Board of Directors shall by a majority vote of a quorum thereof elect a chairman other than the Chairman of the Board to preside at meetings of the Board of Directors. The Chairman may sign and execute all authorized bonds, contracts or other obligations in the name of the Corporation; and he or she shall be ex-officio a member of all standing committees.The President shall be the chief executive officer of the Corporation and shall have general charge and control of all its business affairs and properties. He or she shall preside at all meetings of the members.The President may sign and execute all authorized bonds, contracts or other obligations in the name of the Corporation. The President shall have signature power and the authority to assign signature power to the Executive Officer and/or Vice Chair of Conferences to sign checks in amounts up to $5,000. All checks for amounts over $5,000 for costs not associated with contracts and expenses previously approved by the Board of Directors shall require approval of the Board of Directors and the signature of two officers or one officer and one Appointed Officer. The President shall have the general powers and duties of supervision and management usually vested in the office of president of a corporation. The President shall be ex-officio a member of all the Standing committees. He shall do and perform such other duties as may, from time to time, be assigned to him by the Board of Directors.In the event that the membership does not take affirmative action to fill the office of Chairman of the Board, the President shall assume and perform all powers and duties given to the Chairman of the Board by these bylaws.The President-elect may sign and execute all authorized bonds, contracts, or other obligations in the name of the Corporation. The President-elect shall have such other powers and shall perform such other duties as may be assigned to the President-elect by the Board of Directors or by the President. In case of the absence or disability of the President, the duties of that office shall be performed by the President-elect, and the taking of any action by the President-elect in place of the President shall be conclusive evidence of the absence or disability of the President.The Board of Directors may appoint more than one Vice President. Any Vice President (unless otherwise provided by resolution of the Board of Directors) may sign and execute all authorized bonds, contracts, or other obligations in the name of the Corporation. Each Vice President shall have such other powers and shall perform such other duties as may be assigned to the Vice President by the Board of Directors or by the President. In case of the absence or disability of the President and President-elect, the duties of the office of President shall be performed by any Vice President, and the taking of any action by any such Vice President in place of the President shall be conclusive evidence of the absence or disability of the President.The Secretary shall handle all voting matters, whether at actual meetings, telephonic meetings or meetings held on the Internet or other electronic media; he or she shall give, or cause to be given, notice of all meetings of members and Directors and all other notices required by law or by these bylaws, and in case of his or her absence or refusal or neglect to do so, any such notice may be given by any person thereunto directed by the President, or by the Directors or members upon whose written request the meeting is called as provided in these bylaws. The Secretary shall record all the proceedings of the meetings of the members and of the Directors in books provided for that purpose, and he or she shall perform such other duties as may be assigned to him or her by the Directors or the President. He or she shall have custody of the seal of the Corporation and shall affix the same to all instruments requiring it, when authorized by the Board of Directors or the President, and attest the same. In general, the Secretary shall perform all the duties generally incident to the office of Secretary, subject to the control of the Board of Directors and the President.The Treasurer shall oversee the Executive Officer's and/or Vice Chair of Conferences' custody of all the funds and securities of the Corporation, and he or she shall oversee the Executive Officer's and/or Vice Chair of Conferences' full and accurate account of receipts and disbursements in books belonging to the Corporation. The Treasurer shall oversee the Appointed Officers' deposit of all moneys and other valuables in the name and to the credit of the Corporation in such depository or depositories as may be designated by the Board of Directors. He or she shall have the power to sign checks under his or her signature in amounts up to $5,000. All checks for amounts over $5,000 shall require the signature of two officers or one officer and one Appointed Officer.The Treasurer shall oversee the Appointed Officers' disbursement of the funds of the Corporation as may be ordered by the Board of Directors and may require the Appointed Officers to make proper vouchers for such disbursements. The Treasurer shall render to the President and the Board of Directors, whenever either of them so requests, an account of all of the Appointed Officers' transactions and of the financial condition of the Corporation.The Treasurer shall give the Corporation a bond, if required by the Board of Directors, in a sum, and with one or more sureties, satisfactory to the Board or Directors, for the faithful performance of the duties of his or her office and for the restoration to the Corporation in case of his or her death, resignation, retirement or removal from office of all books, papers, vouchers, moneys, and other properties of whatever kind in his or her possession or under his or her control belonging to the Corporation.The Treasurer shall perform all the duties generally incident to the office of the Treasurer, subject to the control of the Board of Directors and the President.The Board of Directors may appoint an Assistant Secretary or more than one Assistant Secretary. Each Assistant Secretary shall (except as otherwise provided by resolution of the Board of Directors) have power to perform all duties of the Secretary in the absence or disability of the Secretary and shall have such other powers and shall perform such other duties as may be assigned to him by the Board of Directors or the President. In case of the absence or disability of the Secretary, the duties of the office shall be performed by any such Assistant Secretary, and the taking of any action by any such Assistant Secretary in place of the Secretary shall be conclusive evidence of the absence or disability of the Secretary.The Board of Directors may appoint an Assistant Treasurer or more than one Assistant Treasurer. Each Assistant Treasurer shall (except as otherwise provided by resolution of the Board of Directors) have power to perform all duties of the Treasurer in the absence or disability of the Treasurer and shall have such other powers and shall perform such other duties as may be assigned to him by the Board of Directors or the President. In case of the absence or disability of the Treasurer, the duties of the office shall be performed by any Assistant Treasurer, and the taking of any action by any such Assistant Treasurer in place of the Treasurer shall be conclusive evidence of the absence or disability of the Treasurer.In the event that the President shall direct the Secretary to obtain a corporate seal, the corporate seal shall be circular in form and shall have inscribed thereon the name of the Corporation, the year of its organization and the word “Delaware”. Duplicate copies of the corporate seal may be provided for use in the different offices of the Corporation but each copy thereof shall be in the custody of the Secretary of the Corporation or of an Assistant Secretary of the Corporation nominated by the Secretary.Such officers or agents of the Corporation as from time to time shall be designated by the Board of Directors shall have authority to deposit any funds of the Corporation in such banks or trust companies as shall from time to time be designated by the Board of Directors and such officers or agents as from time to time shall be authorized by the Board of Directors to withdraw any or all of the funds of the Corporation so deposited in any such bank or trust company, upon checks, drafts or other instruments or orders for the payment of money, drawn against the account or in the name or behalf of this Corporation, and made or signed by such officers or agents; and each bank or trust company with which funds of the Corporation are so deposited is authorized to accept, honor, cash and pay, without limit as to amount, all checks, drafts or other instruments or orders for the payment of money, when drawn, made or signed by officers or agents so designated by the Board of Directors until written notice of the revocation of the authority of such officers or agents by the Board of Directors shall have been received by such bank or trust company. There shall from time to time be certified to the banks or trust companies in which funds of the Corporation are deposited, the signature of the officers or agents of the Corporation so authorized to draw against the same. In the event that the Board of Directors shall fail to designate the persons by whom checks, drafts and other instruments or orders for the payment of money shall be signed, as hereinabove provided in this Section, all of such checks, drafts and other instruments or orders for the payment of money shall be signed by the President or a Vice President and countersigned by the Secretary or Treasurer or an Assistant Secretary or an Assistant Treasurer or Appointed Officer of the Corporation.Such officers or agents of this Corporation as from time to time shall be designated by the Board of Directors shall have authority to effect loans, advances or other forms of credit at any time or times for the Corporation from such banks, trust companies, institutions, corporations, firms or persons as the Board or Directors shall from time to time designate, and as security for the repayment of such loans, advances, or other forms of credit to assign, transfer, endorse and deliver, either originally or in addition or substitution, any or all stocks, bonds, rights and interests of any kind in or to stocks or bonds, certificates of such rights or interests, deposits, accounts, documents covering merchandise, deposits and accounts receivable and other commercial paper and evidences of debt at any time held by the Corporation; and for such loans, advances or other forms of credit to make, execute and deliver one or more notes, acceptances or written obligations of the Corporation on such terms, and with such provisions as to the security or sale or disposition thereof as such officers or agents shall deem proper; and also to sell to, or discount or rediscount with, such banks, trust companies, institutions, corporations, firms or persons any and all commercial paper, bills receivable, acceptances and other instruments and evidences of debt at any time held by the Corporation, and to that end to endorse, transfer and deliver the same. There shall from time to time be certified to each bank, trust company, institution, corporation, firm or person so designated the signatures of the officers or agents so authorized; and each such bank, trust company, institution, corporation, firm or person is authorized to reply upon such certification until written notice of the revocation by the Board of Directors of the authority of such officers or agents shall be delivered to such bank, trust company, institution, corporation, firm or person.Any payments made to an officer or other employee of the Corporation, such as salary, commission, interest or rent, or entertainment expense incurred by him or her, which shall be disallowed in whole or in part as a deductible expense by the Internal Revenue Service, shall be reimbursed by such officer or other employee of the Corporation to the full extent of such disallowance. It shall be the duty of the Directors, as a Board, to enforce payment of each such amount disallowed. In lieu of payment by the officer or other employee, subject to the determination of the Board of Directors, proportionate amounts may be withheld from his or her future compensation payments until the amount owed to the Corporation has been recovered.The fiscal year of the Corporation shall end on the last day of December.Whenever, under the provisions of these bylaws, notice is required to be given to any Director, officer or member it shall not be construed to mean personal notice, but such notice shall be given in writing, by E-mail over the Internet or similar electronic media, by mail, by depositing the same in a post office or letter box, in a postpaid sealed wrapper, addressed to each member, officer or Director at such address as appears on the books of the Corporation, or in default of any other address, to such Director, officer or member at the general post office in the town of La Jolla, California, and such notice shall be deemed to be given at the time the same shall be thus mailed. Any member, Director or officer may waive any notice required to be given under these bylaws.Any notice required to be given under these bylaws or otherwise may be waived by the Director, officer or member to whom such notice is required to be given and the Attendance of any person at a meeting shall constitute waiver of notice thereof as to such person. Any action which may be taken at a meeting of the Directors, officers or members may be taken without a meeting if a consent in writing, setting forth the action so taken, shall be signed by all of the Directors, officers or members entitled to vote with respect to the subject matter thereof. Such consent shall have the same force and effect as a unanimous vote of the Directors, officers or members, as the case may be.Any member can propose an amendment of the bylaws by submitting the change to the President. If a majority of the Board of Directors adopts the amendment it shall be adopted.The Corporation shall indemnify and advance expenses to a Director, officer or Appointed Officer of the Corporation in connection with a proceeding to the fullest extent permitted by and in accordance with the General Corporation Law of the State of Delaware.With respect to an employee or agent, other than a Director, officer or Appointed Officer of the Corporation, the Corporation may, as determined by the Board of Directors of the Corporation, indemnify and advance expenses to such employee or agent in connection with a proceeding to the extent permitted by and in accordance with the General Corporation Law of the State of Delaware.September 16, 2003: Bylaws amended by majority vote of the Board of Directors


The 1980s were not kind to African elephants. Poachers committed brutal acts in the pursuit of tusks to feed the human hunger for ivory. Gruesome images of the carnage they left behind—mutilated corpses sprawled in twisted repose, attended by bereft companions and bewildered orphans—helped document the precipitous collapse of Africa’s elephant populations. Between 1970 and 1989, as global demand for ivory grew and poachers traded traditional hunting methods for AK-47s and elephant guns, an estimated three-quarters of a million elephants were killed, leaving just 600,000 survivors. Much of Africa, once home to as many as 10 million elephants, had turned into an elephant graveyard.This catastrophic decline, coupled with public outcry at the elephants’ cruel fate, led to a ban on the international ivory trade, after the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) placed the African elephant on its most critically endangered list, Appendix I. The ban, which led to more aggressive anti-poaching campaigns and increased investment in wildlife protection, set African elephants on the road to recovery. But a new study from Stephen Blake, Samantha Strindberg, Fiona Maisels, and colleagues warns that while savannah elephants may indeed be rebounding—in part because they live in countries with long histories of wildlife management, where protection is facilitated by open plains habitats and usually good infrastructure—their forest relatives, hidden in the Congo Basin rainforests, still face intense poaching pressure.Humans have exploited elephants’ ivory tusks for profit ever since ancient civilizations recognized the beauty and commercial potential of ivory. Despite increased awareness about the bloody legacy of the illegal ivory trade, consumers outside Africa, particularly in Asia, continue to buy ivory. And despite the 1989 ban, the status and management of African elephants remain precarious, except in southern Africa, where effective management of the savannah elephant has ensured its protection. Countries in southern Africa oppose the Appendix I listing and trade ban, arguing that their savannah elephants have either rebounded or were never threatened, thanks to good management. They want to sell their ivory stockpiles as reward for their success and use the proceeds to underwrite their conservation programs.  CITES approved one-time stockpile sales in 1997 and in 2002; though the 2002 sale has not yet proceeded, pending the completion of necessary monitoring commitments, it may be approved by CITES in June.While the life history and conservation status of savannah elephants are well known, relatively little is known about the biology of forest elephants, which scientists suspect may be a distinct species uniquely adapted to Africa’s dense rainforests. And because central African nations—where ivory poaching persists—have far less capacity for elephant management than southern African nations, conservationists fear that legalizing even limited trade in ivory from southern African elephants will place the forest elephant in serious jeopardy.Unlike most eastern and southern African nations, which have thriving wildlife-based tourism industries and the funding and infrastructure to facilitate elephant protection, Congo Basin forest nations have crumbling infrastructure, poorly supported wildlife departments, and vast areas accessible only by foot. In some nations, high levels of corruption thwart wildlife management, while in the Democratic Republic of Congo, Congo, and the Central African Republic, high-intensity civil conflicts have interfered with management and led to accelerated poaching, often organized by the military. In nations without the law enforcement capacity to catch and prosecute ivory poachers, poaching levels appear to fluctuate with market demand and price. Kenya, which saw rampant elephant poaching in the 1980s, and countries in West and Central Africa, the heart of forest elephant habitat, continue to support the Appendix 1 listing of all African elephants. They worry that even one-off sales will stimulate global demand for ivory, expand the black market for ivory, and increase the incentive to poach.Devising a rational policy for managing elephants that balances the rights of local governments against wildlife conservation requires accurate measures of elephant abundance and distribution and rates of illegal killing across the continent. In savannahs, elephant counts usually involve flying over the plains to count both live individuals and carcasses. But tracking elephants and poachers through the vast, often swampy equatorial rainforest must be done on foot and presents significant methodological and logistical challenges. The last regional forest elephant survey, in 1989, estimated that about 172,000 forest elephants lived in the Congo Basin—suggesting that forest elephants accounted for nearly a third of Africa’s elephants at that time. Forest elephant distribution, the survey found, was primarily affected by the presence of humans and roads.With logging and road-building in the Congo Basin projected to increase dramatically, Blake et al. set out to chart the abundance and distribution of forest elephants across the Congo Basin. Working in conjunction with the CITES Monitoring of the Illegal Killing of Elephants (MIKE) program, the researchers systematically surveyed six protected MIKE sites, national parks expected to have significant forest elephant populations. Between 2003 and 2005, they walked through “some of the most remote and difficult terrain in forested Africa” to survey over 60,000 square kilometers for signs of elephants (dung piles) and humans , to collect data on the abundance, distribution, and illegal killing of forest elephants . Their analysis included data collected during a “megatransect,” a continuous foot survey through 2,000 kilometers of “the most remote forest blocks in Africa,” between northeastern Congo and southwestern Gabon.As expected, illegal killing and other human incursions played a profound role in shaping forest elephant distribution and abundance. Altogether, the researchers found 53 confirmed elephant poaching camps; they found poached elephant carcasses, with tusks removed, in every protected MIKE site. The probability of encountering elephants increased as one traveled away from the nearest major road, while the probability of detecting human signs decreased. The likelihood of discovering poached elephant carcasses also decreased with distance from the nearest road; no poached carcasses were found farther than 45 kilometers from the nearest road.In Salonga National Park—the largest forested national park in Africa, and a UNESCO World Heritage Site in the remote heart of the Democratic Republic of Congo—Blake et al. report as few as 1,900 elephants remain. Only two national parks had a mean estimated density of more than one elephant per square kilometer, Minkébé and Odzala-Koukoua, and these sites contain the largest tracts of remote wilderness left in the entire Congo Basin. The overwhelming trend from both the MIKE surveys and the megatransect was that elephants were more abundant with increasing distance from a road and decreasing evidence of humans.How could Salonga National Park, with three times the area of any other park surveyed, have so few elephants? Most likely because the park is divided into two sections, and is crisscrossed with old roads and navigable rivers, placing nearly half of its area within ten kilometers of an access point. In contrast, the two parks with remote areas over 60 kilometers from the nearest roads had elephant densities over ten times that of Salonga.Since the megatransect survey included both protected and unprotected areas over a large geographical scale, the researchers could determine what effects, if any, protected status has on the number and distribution of forest elephants and on the presence of humans. As in the analysis of the protected MIKE sites, the probability of encountering elephants increased with distance from a road, but at any distance from a road the probability of encountering elephants was higher in protected areas than in forest outside of protected areas. Protected areas, even those with limited management capacity, have a positive influence by attenuating rates of illegal killing.Overall, these results show that forest elephants are in deep trouble—their range and numbers are shrinking as poachers continue to kill them for their tusks (and probably their meat). As logging road infrastructure explodes across the Congo Basin, the area of remote wilderness is decreasing rapidly, allowing poachers access to the last herds in the depths of the forest. Large areas of wilderness are critical for the survival of forest elephants, and important if human–elephant conflict is to be minimized, yet they are disappearing fast.Given that this study describes the situation in and around well-established protected areas and remote forest, the researchers point out that the conservation status of forest elephants is probably “considerably worse” in the rest of the Congo Basin, where wildlife management resources are scarce. Legalizing the ivory trade based on the recovery of savannah elephants will only accelerate the forest elephants’ decline, unless a change in trade status of southern African elephants comes with a strong commitment from CITES and ivory-trading nations to work with central African nations to reinforce elephant management capacity.What can be done to save the forest elephant? Given that protected areas tend to have more elephants and less people, the preservation of the forest elephant depends on improving management capacity in large, remote, well-managed national parks throughout their range in the Congo Basin. Preventing further declines will require beefed-up law enforcement to stop poaching and rein in the illegal ivory trade, carefully regulated road-building to preserve contiguous forest, and collaborations with logging and mining companies to reduce their impacts on protected areas and to improve ecosystem management and elephant protection in their concessions. Ultimately, consumers of unsustainable and illegally traded ivory must be educated to understand that their actions leave bloody, rotting carcasses in the depths of the forest. Illegal trade provides precious little benefit to the usually poor poacher, who may kill a six-ton elephant with 30-kilogram tusks worth thousands of dollars on the international market for the “salary” of a pair of shorts and a packet of cigarettes from an ivory-trading middleman.http://www.wcs.org/international/Africa/africanelephants or http://www.iucn.org/themes/ssc/sgs/afesg/aed/aesr2002.html.While the elephant clearly awakens the darker side of humanity, willing to lay waste a giant beast for the sake of its tusk, one can only hope that it can also inspire the human capacity for wisdom—and the understanding that the world would be a poorer place without every incarnation of what Donne called “nature’s great master-peece.” For more information on African elephants, visit


To determine the prevalence, intensity and extent of the Oral Impacts on Daily Performances associated with self-perceived malocclusion among Peruvian schoolchildren.(Peru)Child-OIDP was used to assess the prevalence, intensity and extent of oral impacts on 8 daily performances . Self-perceived malocclusion included complaints about position of teeth, spacing of teeth and deformity of mouth or face. The prevalence of oral impacts was compared by covariables using the Chi-square test, whereas the intensity and extent of oral impacts were compared by covariables through the Mann-Whitney test.Eight hundred and five children aged 11 to 12 years attending 4 of 7 randomly selected schools linked to a Health Centre in Lima, Peru, participated in the study. The Spanish Only 15.5% of children reported impacts associated with self-perceived malocclusion during the last 3 months. Of them, 18.4% reported impacts of severe or very severe intensity and 76.0% reported impacts on only one daily performance. Psychosocial activities such as smiling, emotion and social contact were the most frequently and severely impacted everyday activities.Impacts of self-perceived malocclusion primarily affected psychological and social everyday activities. These findings provide further evidence to support the importance of psychological and social components of oral health on children's lives. A better knowledge about the physical, social and psychological effects of malocclusion is important since it provides insights into the perceived impacts of malocclusion on children's lives ,2. To daSpecific OHRQoL measures are designed for use in clinical situations. Their narrow focus means that they are potentially more responsive to small, but clinically important, changes in health ,4,5. SpeCondition-specific instruments are the most commonly used specific measures to assess quality of life . The advPrevious studies assessing the impact of malocclusion on children or adolescents have only reported on the prevalence of impacts on quality of life -16. No sThe study was carried out within the area related to the Mother-Child Health Centre of Zapallal in Puente Piedra . There are 7 public schools in this jurisdiction. In 2006, 1519 children aged 11 to 12 years (born in 1995 and 1994 respectively) attended these schools. 4 of these 7 schools were randomly selected as clusters, and all their 903 11-12-year-old children were invited to participate in the study. Ethical approval was obtained from the International Review Board at the Universidad Peruana Cayetano Heredia. Parents signed a consent letter accepting participation of their children. Children also gave written consent for interviews.(Peru)Child-OIDP were evaluated. For criterion validity, the Spanish (Peru)Child-OIDP scores were significantly associated with self-perceived oral health status, self-perceived dental treatment need and satisfaction with oral health status . For internal reliability, all inter-item correlations were positive and statistically different from zero (p ≤ 0.007), whereas the Cronbach's alpha coefficient was 0.62 and did not increase when any performance was deleted. Finally, test-retest reliability was evaluated through intraclass correlation coefficient, whose value was 0.85.Before data collection, the original English version of the Child-OIDP was cross-culturally translated and adapted into Spanish. Then, the validity and reliability of the Spanish The Child-OIDP was administered through individual interviews, except for the first question that was self-administered in a classroom setting. The children were first asked to provide socio-demographic information related to their sex, age and education level (e.g. primary or secondary school), and then, to identify problems with their mouth or teeth perceived during the last 3 months. Thereafter, 2 trained interviewers carried out individual face-to-face structured interviews. Oral impacts on daily life were assessed in relation to 8 daily performances namely, eating, speaking, mouth cleaning, sleeping, smiling, studying, emotion and social contact. If children reported an impact on any performance, the frequency of the impact  and the severity of its effect on daily life  were scored . If no iThe impact per daily performance was estimated by multiplying the corresponding frequency and severity scores. The overall CS-Child-OIDP score was the sum of the 8 performance scores (ranging from 0 to 72) multiplied by 100 and divided by 72 . Then, tFor the statistical data analysis, the prevalence of condition-specific impacts was compared according to sex, age and education level using the Chi-square test. The intensity and extent of condition-specific impacts were compared according to covariables using the Mann-Whitney test. Non-parametric tests were used to compare intensity and extent because the former was measured using an ordinal scale and the latter was not normally distributed in the sample .Eight hundred and five of the 903 11–12 year-old children attending the 4 selected schools participated in the study; a response rate of 89.1%. Fifty one percent (51.2%) were female and 48.8% male; 53.5% were at primary education and 46.5% at secondary education level. The mean age of the children was 11.93 ± 0.63 years.95%]. The most frequently reported oral condition related to malocclusion was position of teeth (28.4%), followed by spacing of teeth (16.3%) and deformity of mouth or face (1.6%). The prevalence of self-perceived malocclusion did not differ by sex or age (p = 0.275 and 0.057 respectively). However, there was a significant difference of perceived malocclusion by education level (p = 0.021) ]. The most common daily performances affected by malocclusion were smiling and emotion (9.1% and 3.2% respectively). The prevalence of condition-specific impacts on the other evaluated 6 daily performances was less than 2.0% ] reported impacts of severe or very severe intensity ], with 76.0% of children with condition specific impacts reporting 1; 19.2% reporting 2, 3.2% reporting 3, 0.8% reporting 4 and 0.8% reporting 5 performances affected. None reported condition-specific impacts on 6 or more of the 8 daily performances. No statistically significant difference was found when the extent of the condition-specific impacts was compared by covariables   and maintaining the usual emotional state without being irritable. Other psychosocial activities such as carrying out schoolwork  and relaxing/sleeping  were the least frequent and least severely impacted. These findings highlight the importance of the psychological and social aspects of the teeth and mouth on children's lives. Teeth mainly affect social interaction with peers, where satisfaction with dental appearance plays a very important role ,20,26.Interference with predominantly physical activities such as eating and enjoying food, speaking clearly and cleaning mouth  were only reported by between 1.3% and 1.9% of the children. It has been reported that dissatisfaction with ability to chew was less often a reason for seeking orthodontic treatment because problems with chewing may be less common than problems related with dental appearance ,27. ThesMore than three-quarters of the children with impacts had only one daily performance affected. The performances affected were mainly related to smiling, laughing and showing teeth without embarrassment. Eating, sleeping and studying were not frequently affected. No child reported impacts on more than 5 daily performances. The findings support the view that children with a perceived malocclusion are more concerned with dental aesthetics than with function. Therefore, psychological factors, such as dental aesthetics, self-perception of dental appearance, rather than the severity of the clinical occlusal condition, most probably determine children's demand for orthodontic treatment ,28.The Child-OIDP measures impacts on the ultimate level of the oral impacts ,29, equiIf the figures reported here were used for orthodontic services planning, the estimates of orthodontic treatment need would likely be lower than those obtained using normative indexes alone ,14,15. UAlthough it has been argued that the physical, social and psychological effects are important reasons why orthodontic care is sought , our fin- Only 15.5% of the interviewed children reported impacts associated with self-perceived malocclusion during the last three months. Among children with impacts, 18.4% reported impacts of severe or very severe intensity and 76.0% had impacts on only one daily performance.- Among children with impacts, psychosocial activities such as smiling, emotion and social contact were the most frequently and severely impacted. These findings provide further evidence in support of the importance of psychological and social components of oral health children's lives.- Education level was the only demographic variable that significantly affected the prevalence of self-perceived malocclusion and intensity of the impacts associated with self-perceived malocclusion.The author(s) declare that they have no competing interests.Eduardo Bernabé conceived of the study, was responsible for the data collection in Peru, conducted the statistical analysis and was responsible for the completion of the whole manuscript. Carlos Flores-Mir was consulted for methodology and revised the manuscript. Aubrey Sheiham contributed to the conception and design of the study and critically revised the manuscript. All authors read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:


However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1α−/− mice. With age, the PGC-1α−/− mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1α−/− mice, leading to reduced muscle performance and exercise capacity. PGC-1α−/− mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1α−/− mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1α−/− mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1α−/− mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1α−/− mice. These results demonstrate that PGC-1α is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was targeted in mice. PGC-1α null (PGC-1α Eliminating the activity of the gene PGC-1 α in mice reveals its role in post-natal metabolism and provides a link to obesity and some intriguing differences with another report of this knockout Mitochondrial functional capacity is dynamically regulated to meet the diverse energy demands imposed on the mammalian organism following birth. Postnatal mitochondrial biogenesis involves multiple signaling and transcriptional regulatory pathways that control the coordinate expression of nuclear and mitochondrial genes involved in mitochondrial structure, metabolism, and proliferation . Recent Several lines of evidence, based on the results of overexpression studies, indicate that PGC-1α is sufficient to promote mitochondrial biogenesis and regulate mitochondrial respiratory capacity. First, PGC-1α activates the transcription of mitochondrial uncoupling protein-1 (UCP-1) in BAT through interactions with the nuclear hormone receptors PPARγ and thyroid receptor . Second,PGC-1α gene have been shown to be associated with obesity, hypertension, and diabetes ) supplemented with 50 μg/ml saponin and permeabilized for 30 min at 4 °C with gentle stirring. Fibers were then washed twice for 10 min each . Respiration was measured at 25 °C using an optical probe . Following measurement of basal state 2 respiration, maximal (ADP-stimulated) state 3 respiration was determined by exposing fibers to 1 mM ADP. The integrity of the outer mitochondrial membrane was assessed by adding 8 μM exogenous cytochrome c to ADP-stimulated fibers. State 4 respiration (uncoupled) was evaluated following addition of oligomycin (1 μg/ml). The solubility of oxygen in the respiration buffer at 25 °C was taken as 246.87 nmol O2 · ml−1. Respiration rates were expressed as nmol O2 · min−1 · mgdw−1.Mitochondrial respiration was assessed in saponin-skinned soleus fibers with succinate as substrate and in the presence of rotenone as previously described . In brieGlucose and Insulin tolerance tests were performed as described . Prior t2) of 5-wk-old female mice were measured using a Columbus Instruments Oxymax System. Resting baseline oxygen consumption rates were assessed for at least 1.0 h. For β3-adrenergic stimulation studies, BRL 37344 (Sigma) was dissolved in sterile saline and injected IP (2 μg/g of body weight) -palmitic acid as described . Hearts were cannulated first via the aorta and perfused retrogradely by the Langendorff method. Following left atrial cannulation, perfusion was switched to the working mode with KHB solution containing 1.2 mM palmitate bound to 3% fatty acid-free BSA with a preload pressure of 11.5 mm Hg and an afterload pressure of 50 mm Hg for 60 min with oxygenated buffer solution. Functional measurements, namely cardiac output, aortic flows, peak systolic pressure, and heart rate were acquired every 10 min using inline flow probes , a pressure transducer  and data acquired with the MP100 system from AcqKnowledge (BIOPAC Systems). Cardiac work was calculated as the product of peak systolic pressure and cardiac output.Isolated working mouse heart perfusion was based on a previously described procedure . Adult mp < 0.05 in all cases. Data are reported as mean values ± SEM, unless otherwise noted. The ANOVA model used to analyze each sensorimotor test included one between-subjects variable (genotype), and one within-subjects variable . When ANOVAs with repeated measures were conducted, the Huynh-Feldt (H-F) adjustment of alpha levels was used for all within-subjects effects containing more than two levels, in order to protect against violations of the sphericity/compound symmetry assumptions underlying this ANOVA model. In addition, Bonferroni correction was used when appropriate to help maintain prescribed alpha levels  when multiple comparisons were conducted.Data were analyzed using T-tests or ANOVAs . The level of significance was set at Figure S1+/+ (n = 4) and PGC-1α−/− (n = 3) female mice were monitored for 48 h after a 17-h period of acclimation. XY beam breaks were tabulated over the 12-h light and dark cycles as denoted on the bottom. The bars represent mean (± SEM) beam breaks per each 12-h cycle.Using a CLAMS system, PGC-1α(342 KB EPS).Click here for additional data file.Figure S2p < 0.05 compared to the PGC-1α+/+ mice.An analysis of exploratory behavior included the number of entries into the center of the cage (upper left), the time spent in the center of the cage in seconds (sec) (upper right), the distance traveled in the center of the cage in meters (m) (lower left) as well as the distance traveled in the periphery (lower right). * (620 KB EPS).Click here for additional data file.Figure S3+/+ (n = 8) and PGC-1α−/− (n = 11) mice. NS, not significant.8-wk-old female mice were fed a diet high in fat  for 6 wk. The change in body weight (grams) after 6 wk on a high-fat diet is shown for PGC-1α(264 KB EPS).Click here for additional data file.Figure S4+/+ (n ≥ 6) and PGC-1α−/− (n ≥ 6) mice were fed a high-fat diet  beginning at 4 wk of age. Body weight was monitored weekly as shown on the graph on the left. The mean (± SEM) change in body weight is shown in the bar graph on the right. *, significant difference compared to the PGC-1α+/+ controls, p < 0.05.Male and female PGC-1α(794 KB EPS).Click here for additional data file.Table S1Sequences of mouse-specific probes and primers used for real-time RT-PCR.(25 KB DOC).Click here for additional data file.http://www.ncbi.nlm.nih.gov/) accession numbers of the vector discussed in this paper is p1339-PGK-Neomycin targeting vector (AF335420).The GenBank (


Evaluation of the relative merits of medical versus surgical management of vesicoureteral reflux (VUR) has been limited by the few prospective studies comparing these strategies. Among those trials that have been reported, the only consistent positive finding has been that incidence of febrile UTI is lower among children undergoing surgical treatment in comparison with medical treatment. Studies have not found significant differences in overall incidence of UTI, or in rates of new renal scarring or progression of existing scarring. It is likely that there is a subset of children with VUR who do benefit from aggressive treatment of their VUR, but we are not yet able to fully determine which children these are. It is hoped that future research will further clarify which treatments are useful in which children.  Urinary tract infection (UTI) is one of themost common serious bacterial infections in children. Cumulative incidence is1–2% among boys and 3–7% among girls, and between 70 000 to 180 000 of theannual US birth cohort will have a UTI by the age of 6 [In addition to itsassociation with UTI, VUR is also a highly genetic condition, displaying anautosomal dominant transmission pattern, with variable penetrance. VUR mayoccur in up to 66% of the offspring of VUR patients , and theIt has long beenappreciated that there is an association between recurrent UTI, VUR and renalparenchymal scarring . The traIn general, mostmanagement strategies for VUR have sought to address and defeat this process atvarious points along the pathogenic sequence. Medical management withantimicrobial prophylaxis seeks to maintain sterile urine, rendering the VURitself relatively harmless, since there are no bacteria present to reach andinvade the kidney. Antireflux surgery (ARS), in contrast, reconfigures the ureterovesicaljunction anatomy to block access to the upper tracts, so that any episodes of cystitisthat do occur cannot progress to pyelonephritis.However, this modelhas been called into question in recent years by data that challenges many ofthe assumptions of the VUR paradigm. Long-term studies show that renal scarringcan occur in children without VUR, and that renal scarring is not common inchildren with even high degrees of reflux , 8. RusAs we will seebelow, it has been difficult to demonstrate that current management strategies forVUR result in measurably improved outcomes. Since these management strategies arebased on assumptions about the pathophysiology of UTI, VUR, and renal scarring,if such assumptions are incorrect then it should not surprise us that ourinterventions seem to have little or no effect.The use of antimicrobials to reducerecurrent and/or chronic UTI's dates back to the 1940's and 50's, and is the mainstay of initial management in children diagnosedwith VUR. Based on the perception that antimicrobial prophylaxis is safe, effective,and easily tolerated, generations of children with VUR have spent yearsundergoing this treatment while awaiting the spontaneous resolution of theirVUR. The classic studies of Smellie et al. form much of the basis for prophylaxis as a management tool , 5, 12. As a consequence,antimicrobial prophylaxis lacks basic evidence of efficacy in prevention ofeither UTI or renal scarring. Three randomized controlled trials comparingantimicrobial prophylaxis with no treatment (surveillance only) have beenreported –15, and Since the initial report of surgical correctionof VUR by Hutch in 1952 , numerouThe extraordinarysuccess of modern ARS might lead one to assume that there is little room leftfor technical innovation in this field. However, investigators have long soughta less invasive way to correct VUR. In 1981, the first injection technique wasreported by Matouschek using polytetrafluoroethylene  paste .ConcernTo our knowledge,there have not been any prospective trials of surgical management compared withobservation in children with VUR. Therefore, we simply do not know if ARS issuperior to surveillance alone in prevention of UTI or renal scarring. Becauseactive management of VUR (either with antibiotics or surgery) is consideredstandard of care, it is difficult to find patients who have truly been given notreatment for their VUR, even in a retrospective review.Comparison of medical treatment withsurgical treatment for VUR is challenging because the different studies haveused various outcome measures, and even studies using similar outcome measuresmay be difficult to compare due to differing definitions of similar outcomes.Reported outcomes in many studies include postoperative incidence of any UTI, incidenceof febrile UTI , andrenal cortical abnormalities (scarring).In a recentmetaanalysis of clinical trials, Hodson et al. identified seven randomizedcontrolled trials comparing surgical and medical management –35, and There was no difference in incidence of any UTI between treatment groups, withincidence of 29–42% in antibioticonly group and 25–40% in thesurgical group . Thus, sReported in only 2 studies, this is the only outcome where significantdifferences in outcomes have been observed between treatments , 37. TheIn the five studies that assessed renal parenchymal abnormalities usingIVP criteria , 33, 38,There is little strong evidence supporting the hypothesis that earlydetection and treatment of VUR is of any benefit, primarily because it has beenso difficult to demonstrate any benefit from the available therapies. Perhapsthe one firm conclusion we can draw from the literature described above isthat, among children with VUR who have had breakthrough febrile UTI's while onantimicrobial prophylaxis, ARS is an appropriate therapy that can be expectedto reduce the incidence of such febrile episodes. However, neither prophylaxisnor ARS can be reliably stated to reduce the risk of new or progressive renalscarring, although it is prevention of this outcome that is widely assumed tobe the most important benefit of VUR treatment.It is plausiblethat, while treatment of VUR may reduce the risk of negative outcomes in asmall subset of VUR patients, the number needed to be treated ; it may be so high as to make the intervention unjustified for theoverall VUR population. For this reason, ongoing research into biomarkers thatwill indicate those at highest risk for recurrent infection and progressiverenal damage is crucial; such biomarkers would allow us to narrow the field ofcandidates for medical or surgical treatment to those most likely to benefit,and allow the larger VUR population to escape the morbidity and bother associatedwith these treatments.Finally, there hasbeen much recent discussion about whether the availability of endoscopic ARSshould alter the indications for ARS. Suggestions have begun to appear in theliterature and at national meetings that endoscopic treatment should beutilized as initial therapy for patients diagnosed with VUR. Advocates arguethat immediate endoscopic therapy is preferable to antimicrobial prophylaxis inchildren just diagnosed with VUR . Currentn = 600) will provide us with superb data regarding risk ofUTI and renal scarring in children with VUR in the short term, as well asdemonstrate whether antimicrobial prophylaxis is effective in preventing eitherUTI or scarring. Other studies assessing the utility of ARS in various clinicalscenarios are desperately needed. Until such studies are complete, clinicianswho treat children with VUR will continue to rely on clinical judgment,experience, and intuition to manage their young patients.Ongoing clinicalstudies will hopefully clarify some of the glaring shortcomings in our evidencebase. The NIDDK-funded RIVUR study is a randomized trial of antimicrobialprophylaxis versus placebo in children with VUR and UTI . Each su