Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Suppression of Emittance Growth Using a Shaped Cold Atom Electron and Ion Source.

We demonstrate precise control of charged particle bunch shape with a cold atom electron and ion source to create bunches with linear and, therefore, reversible Coulomb expansion. Using ultracold charged particles enables detailed observation of space-charge effects without loss of information from thermal diffusion, unambiguously demonstrating that shaping in three dimensions can result in a marked reduction of Coulomb-driven emittance growth. We show that the emittance growth suppression is accompanied by an increase in bunch focusability and brightness, improvements necessary for the development of sources capable of coherent single-shot ultrafast electron diffraction of noncrystalline objects, with applications ranging from femtosecond chemistry to materials science and rational drug design.

Classification of neurological abnormalities in children with congenital melanocytic naevus syndrome identifies magnetic resonance imaging as the best predictor of clinical outcome.

BACKGROUND: The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much wider variation in outcome. OBJECTIVES: To establish whether routine MRI of the CNS is a clinically relevant investigation in children with multiple CMN (more than one at birth), and to subclassify radiological abnormalities. METHODS: Of 376 patients seen between 1991 and 2013, 289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has been more than one CMN at birth, independent of size and site of the largest naevus. Cutaneous phenotyping and radiological variables were combined in a multiple regression model of long-term outcome measures (abnormal neurodevelopment, seizures, requirement for neurosurgery). RESULTS: Twenty-one per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the most significant predictor of all outcome measures. Abnormalities were subclassified into group 1 'intraparenchymal melanosis alone' (n = 28) and group 2 'all other pathology' (n = 18). Group 1 was not associated with malignancy or death during the study period, even when symptomatic with seizures or developmental delay, whereas group 2 showed a much more complex picture, requiring individual assessment. CONCLUSIONS: For screening for congenital neurological lesions a single MRI in multiple CMN is a clinically relevant strategy. Any child with a stepwise change in neurological/developmental symptoms or signs should have an MRI with contrast of the brain and spine to look for new CNS melanoma.

Developmental plasticity as a cohesive evolutionary process between sympatric alternate-year insect cohorts.

Many species, particularly insects, pass through a series of distinct phases during their life history, with the developmental timing directed towards appropriate resources. Any factor that creates variation in developmental timing may partition a population into discrete populations-or 'cohorts'. Where there is continued failure to recruit outside the natal cohort then alternate cohorts will have their own internal dynamics, eventually leading to independent demographic and evolutionary trajectories. By contrast, continued variation in development rates within a cohort-cohort splitting-may homogenise otherwise independent demographic units. Using a panel of 14 microsatellite loci, we quantify the genetic signature of apparent demographic isolation between coexisting, but alternate, semivoltine cohorts of the damselfly Coenagrion mercuriale at locations that span its distribution in the UK. We find consistently low levels of genetic divergence between sympatric cohorts of C. mercuriale, indicative of developmental plasticity during the larval stage (unregulated development) whereby some individuals complete their development outside the predominant 2-year (semivoltine) period. Thus, individuals that alter their developmental rate successfully recruit to a different cohort. Despite maintaining contrasting population sizes, gene flow between alternate cohorts broadly is sufficient to place them on a similar evolutionary trajectory and also buffers against loss of genetic diversity. Such flexible larval development permits a response to local conditions and may facilitate response to environmental change.

Primary bone tumors in birds: a review and description of two new cases.

Primary bone tumors are only occasionally reported in avian species. This paper presents the cases of an osteosarcoma in a 6-yr-old free-range chicken and a chondrosarcoma in a 3-yr-old barred Plymouth Rock chicken. The well-differentiated, moderately productive osteoblastic osteosarcoma arose from the synsacral vertebrae and had metastasized to the liver. The chondrosarcoma was well differentiated and firmly attached to the left side of the keel. There was no evidence of metastasis.

Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours.

BACKGROUND: Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T. METHODS: From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity. RESULTS: In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype. CONCLUSION: Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age.

A comparative analysis of senescence in adult damselflies and dragonflies (Odonata).

Any population whose members are subject to extrinsic mortality should exhibit an increase in mortality with age. Nevertheless, the prevailing opinion is that populations of adult damselflies and dragonflies do not exhibit such senescence. Here, we challenge this contention by fitting a range of demographic models to the data on which these earlier conclusions were based. We show that a model with an exponential increase in age-related mortality (Gompertz) generally provides a more parsimonious fit than alternative models including age-independent mortality, indicating that many odonates do indeed senesce. Controlling for phylogeny, a comparison of the daily mortality of 35 odonate species indicates that although male and female mortalities are positively correlated, mortality tends to be higher in males of those species that exhibit territoriality. Hence, we show for the first time that territoriality may impose a survivorship cost on males, once the underlying phylogenetic relationships are accounted for.

Empirical evidence of senescence in adult damselflies (Odonata: Zygoptera).

1. Age-dependent increases in mortality have been documented in a variety of species of insect under laboratory conditions. However, while strong statistical evidence has been presented for senescence in vertebrate populations in the wild, we know little about the rate and shape of senescence in wild populations of insects. 2. Odonates (damselflies and dragonflies) provide excellent candidate species for evaluating demographic senescence as they are large enough to be marked individually and they are easily re-sighted without recapture. The prevailing opinion - based entirely on qualitative examination of the declines in log numbers alive with time since marking - is that odonates exhibit age-independent daily survivorship. 3. Here, we examine mark-recapture data on the Azure Damselfly Coenagrion puella over two consecutive seasons. For the first time, we evaluate and compare the fit of quantitative models that not only account for weather-dependent daily variation in daily re-sighting rates, but also age-dependent variation in daily survivorship. 4. Models with age-dependent declines in daily survivorship provide a more parsimonious explanation for the data than similar models without these age-dependent effects. In general, models in which mortality increases in an exponential (Gompertz) fashion explain the mark-recapture sequences more efficiently than a range of alternative models, including those in which mortality increases as a power function (Weibull) or reaches a plateau (logistic). These results are indicative of a general senescent decline in physiological functioning, which is particularly marked after 15 days as a mature adult. 5. Weather (temperature, sun and precipitation) and initial mite load influenced the probability of daily re-sighting. Weather and mite load also influenced daily survivorship, but their effects differed between seasons. 6. Overall, fitting models with age as an explicit covariate demonstrates that odonates do indeed senesce. This contradicts previously held assumptions that Odonata do not exhibit age-dependent survivorship in the wild.

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

BACKGROUND: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF). METHODS: 422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n=111), minimal residual disease (MRD) SRT (n=70) and SRT (n=83) were defined by PSA levels of <0.2, 0.2-0.49 and ⩾0.5 ng ml(-1), respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome. RESULTS: During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P<0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P=0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. CONCLUSIONS: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.

Results of a randomized feasibility study of a low-fat diet.

A 2-year randomized clinical trial was conducted to test whether free-living women aged 45 to 69 years can reduce the fat content of their diet from the typical US level of approximately 39% to 20% of energy from fat, using readily available foods, when given nutritional and behavioral counseling and social support. Three clinical units randomized 303 selected volunteers into intervention (low-fat eating plan) or control (customary diet) groups. The two groups were comparable at baseline. The intervention group received nutrition instruction and behavioral counseling largely in permanent groups of 12 to 15 participants meeting weekly, then biweekly, and finally monthly. At 6 months, they had substantially reduced the mean proportion of total energy from fat from 39.1% to 20.9%, compared with the control group's nonsignificant reduction from 39.0% to 38.1%. At 12 and 24 months, they sustained the reduction of energy from fat. Weight loss and plasma cholesterol level changes in the intervention group supported the self-recorded dietary intake changes. Attendance at intervention sessions averaged 75% during the first 6 months and, subsequently, 60% to 70%. Four-day food records for the randomized women were obtained at 6 and 12 months from approximately 95% and at 24 months from 87%. A clinical trial of a low-fat diet is feasible in women.

Right-sided congestive heart failure in a dog because of a primary intracavitary myocardial lymphoma.

CASE REPORT: A 9-year-old female intact Cocker Spaniel was presented with a history of acute-onset dyspnoea and abdominal distension of 3 days' duration. Ultrasonography revealed pleural, peritoneal and pericardial effusions. Abdominal fluid analysis was consistent with a modified transudate. Echocardiography revealed a large, hypoechoic space-occupying mass within the right atrium. The dog was euthanased and the postmortem examination showed a solid, 40 × 35 × 20 mm broad-based mass arising from the right atrial wall and occluding approximately 90% of the right atrial lumen. Histopathology revealed myocardial lymphoma. There were histologically similar, focal nodules in the lung parenchyma without involvement of other extracardiac sites. There was gross and histological evidence of hepatic congestion and marked distension of the caudal vena cava, consistent with secondary right-sided congestive heart failure. CONCLUSION: This case highlights the need to consider lymphoma as a differential diagnosis for an intra-atrial mass and as a cause of congestive heart failure in the dog.

Peripheral neuropathy in arsenic smelter workers.

We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.

Transmission dynamics of Bacillus thuringiensis infecting Plodia interpunctella: a test of the mass action assumption with an insect pathogen.

Central to theoretical studies of host-pathogen population dynamics is a term describing transmission of the pathogen. This usually assumes that transmission is proportional to the density of infectious hosts or particles and of susceptible individuals. We tested this assumption with the bacterial pathogen Bacillus thuringiensis infecting larvae of Plodia interpunctella, the Indian meal moth. Transmission was found to increase in a more than linear way with host density in fourth and fifth instar P. interpunctella, and to decrease with the density of infectious cadavers in the case of fifth instar larvae. Food availability was shown to play an important part in this process. Therefore, on a number of counts, the usual assumption was found not to apply in our experimental system.

Nontreatment and aggressive narcotic therapy among hospitalized pancreatic cancer patients.

OBJECTIVES: Strong feelings about patient autonomy as expressed in living wills, polls, and legislative referenda have been challenging the medical establishment to increase nontreatment, defined as foregoing a life-prolonging treatment, and even to provide treatments having life-shortening potential to selected patients. Because there are little data about the actual practice of these procedures, including aggressive narcotic therapy as defined herein, we studied the terminal management of 417 pancreatic cancer patients. DESIGN AND PARTICIPANTS: The medical records of 417 residents of King County, Washington, who died of pancreatic cancer in the time periods 1959-1962, 1969-1972, and 1985-1990, were reviewed to study the frequency of, and risk factors for, end-of-life nontreatment decisions and aggressive narcotic therapy decisions, defined here as the decision to administer treatment doses of narcotics or major sedatives to already comatose patients within 4 hours of death. RESULTS: Antibiotics were not provided to 71% of the 70 febrile patients (two readings >38.33-38.83 degrees C or one reading of 38.88 degrees C), intravenous fluid was not provided to 43% of 294 dehydrated patients (oral intake <500 mL/24 hours), transfusions were not provided to 39% of 57 severely anemic patients (hematocrit <20%), and laparotomy was not performed for 86% of 36 patients with abdominal emergencies (obstruction, bleeding, dehiscence). Also, 46% of the 118 patients who were comatose for at least 24 hours before death received aggressive narcotic therapy, as defined above. A total of 335 of the 417 patients had documentation of at least one of the above life-threatening conditions or were comatose for at least 24 hours before death, and 289 (86%) of these patients experienced nontreatment of one or more of these conditions or received aggressive narcotic therapy. Nontreatment decisions for febrile, dehydrated, or anemic patients tended to be more frequent if the patient was comatose (P=.004, .010, and .065, respectively), if there was a nontreatment statement in the medical record (P=.009, .035, and .001, respectively), or if the patient was described as terminal (P=.262, .029, and .002, respectively). Aggressive narcotic therapy in comatose patients was more common among patients who had regular visitors (P=.002), who had pre-coma pain (P=.006), who had nontreatment statements in their charts (P=.031), whose in-charge physician was an oncologist (P < .001), who were treated in a community nonprofit hospital compared with a Catholic hospital (P=.007), or who were treated in recent years (P=.011). CONCLUSION: Both nontreatment and aggressive narcotic therapy forms of medical management have been occurring commonly in terminal pancreatic cancer patients in King County, Washington, during the past 3 decades, the latter with greater frequency in recent years.

Prophylactic insulin in the management of gestational diabetes.

One hundred eight gestational diabetics were randomized to receive either diet alone or diet plus insulin (20 units NPH and 10 units regular) for glycemic control. Blood glucose levels were evaluated weekly in a high-risk clinic where medical and nutritional support and counseling were provided. Among 68 women successfully treated for a minimum of 6 weeks, the mean birth weight, macrosomia rate, and ponderal index were reduced significantly in the insulin-treated group. Insulin reduced birth weights significantly in women with a delivery weight of 200 lb or more (4060 +/- 342 versus 3397 +/- 640 g) and in those with a delivery weight less than 200 lb (3324 +/- 448 versus 3047 +/- 394 g). No patient with good glucose control and a maternal delivery weight under 200 lb had a newborn over 4000 g. Patients failing glycemic control were at greatest risk (30%) for fetal overgrowth whether initially receiving insulin or not. Maternal obesity or failure to achieve glycemic control should alert the clinician to a substantially increased risk of macrosomia.

Residual embryos in failed embryo transfer.

One hundred thirteen embryo transfers (ETs) were performed in an in vitro fertilization and ET program of which residual or extruded embryos were found in 17 transfers (15%). Residual or extruded embryos are those embryos found outside the uterine cavity, either at the cervical os, on the vaginal speculum, or remaining in the catheter after an ET. Patients were divided into two groups according to the method of inspection for residual embryos. In group I, microscopic visualization of the transfer catheter alone revealed that 9 of the 67 transfers (13.4%) had 17 residual embryos either at the catheter tip or adherent to mucus on the side of the catheter. In group II inspection of the catheter and cervical wash revealed that 8 of 46 ETs (17.4%) had 15 residual embryos that failed to be transferred during the initial attempt. Six of these 15 (40%) were found in the cervical wash medium. Thus, failure of the proper placement of embryos at the time of transfer may occur frequently. Evaluation of only the transfer catheter may result in a significant underestimation of the problem.

X-ray beam characteristics of the Varian Clinac 6-100 linear accelerator.

Beam characteristics and dosimetry measurements of the 6 MV x-ray beam from a Varian Associates Clinac 6-100 linear accelerator are presented. Percentage depth dose tables are given as a function of field size for square fields. Tissue-maximum ratios and scatter-maximum ratios are tabulated as a function of depth and field size. Investigation of surface dose and depth of maximum dose reveal a dependence on field size. Other beam parameters measured are presented include field flatness, symmetry, SSD dependence, and penumbra. Treatment planning parameters including field size output factors and wedge factors are discussed.

Identification of cyclo(His-Pro)-like immunoreactivity in human follicular fluid: correlation with steroid and peptide hormones.

OBJECTIVE: The purpose of this study was to evaluate human follicular fluid (FF) for the presence of cyclo(His-Pro)-like immunoreactivity (CHP-LI). After verifying its presence, we quantitated the levels and investigated correlations with other follicular parameters, including hormone levels. METHODS: Follicular fluid was collected from female volunteers undergoing controlled ovarian hyperstimulation. Fluid was collected by follicular puncture, either transvaginally (in vitro fertilization) or laparoscopically (gamete intrafallopian transfer) at the time of oocyte retrieval (N = 137). Follicular size was determined ultrasonographically. Assays for steroid and peptide hormones were determined with commercially available radioimmunoassay kits. CHP-LI was measured using a previously reported assay; parallel dilution curves and column chromatography aided in immunoidentity. RESULTS: The mean FF CHP-LI concentration (13.10 +/- 1.83 nmol/L, N = 137) was greater than the corresponding serum values (9.42 +/- 2.45 nmol/L; N = 21) (P < .05). Large follicles (20 mm or greater; 14.45 +/- 1.74 nmol/L) contained significantly more CHP-LI than either medium follicles (16-19 mm; 11.51 +/- 1.88 nmol/L) or small follicles (15 mm or smaller; 10.83 +/- 2.12 nmol/L) (P < .05). Positive correlations were found between FF CHP-LI values and corresponding FF progesterone and prolactin concentrations (r = 0.67 and 0.62, respectively; P < .05). CONCLUSION: Mean CHP-LI levels in the FF are greater than those in the corresponding serum. We suggest that the neuropeptide may be originating from either peptidase cleavage of precursor peptides or from granulosa cell production.

A chemical hypothesis for arsenic methylation in mammals.

The toxicology of arsenic is complicated by its ability to convert between oxidation states and organometalloidal forms. These processes cause differences in the relative tissue-binding affinities of the various arsenic species, and they determine both the intoxication and the detoxification mechanisms. In this review, a chemical hypothesis of arsenic biomethylation is developed from an examination of data and observations presented by researchers who conducted numerous in vivo and in vitro experiments. It is likely that a combination of pathways is actually used during methylation of arsenic in vivo, and that the principal mechanism depends on various factors affecting the cellular environment. Despite these uncertainties, several observations can be made: (i) glutathione (GSH) is required for reduction of arsenic(V) to arsenic(III) species in preparation for enzyme-catalyzed oxidative methylation; (ii) GSH is not involved in monomethylation once arsenite is formed, but GSH is involved in dimethylation by reducing methylarsonic acid [MMA(V)] to methylarsonous acid [MMA(III)]; (iii) GSH is also required in the methylation of arsenic by stabilizing the reductive nature of the cell; (iv) a different methyltransferase is used in each methylation step; (v) dithiols (either a cofactor or the methyltransferases) are required for both mono- and dimethylation and (vi) where dithiols are involved, oxidative methylation reduces the stability of the arsenic-sulfur complex and permits dissociation of the arsenic species. This lower affinity of the pentavalent organoarsenic species for dithiols is part of the reason why methylation of arsenic can be a detoxification mechanism when the As(III) intermediates are not permitted to accumulate.