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Background: Immunotherapy has drastically changed the outlook for melanoma patients over the past decade. Specifically, the dual blockade of immune checkpoints using ipilimumab and nivolumab has shown unprecedented response rates and survival outcomes. This immense achievement, though, is at the cost of toxicity, with 60% of the patients experiencing high-grade adverse events (AEs). Our study aims to report the efficacy and toxicity outcomes of an out-of-trial, real-life population. Methods: Data on metastatic melanoma patients treated with ipilimumab and nivolumab were retrieved from our melanoma database-a single-center prospectively updated, medical-records based oncologic registry. Data included demographics, clinical and pathological information, as well as tumor responses and survival. Associations between patient or treatment characteristics and outcomes were also evaluated. Results: We identified 172 metastatic melanoma patients, of whom 64% were treatment-naïve. The median follow-up was 12 months. The response rates for treatment-naïve and previously-treated patients were 61% and 25%, respectively; median progression-free survival (PFS) were 12.2 and 2.6 months, and median overall survival (OS) were not-reached (NR) and 6.1 months, respectively. The estimated three-year OS for treatment-naïve patients was 58% (95% CI 42-65). At data cutoff, 22% were still on-treatment. Grade 3-4 adverse events (AEs) were reported in 60% of the patients, almost all of whom were exposed to steroid treatments (59%); AEs were fatal in 4 patients, and led to permanent treatment discontinuation in 31%. Factors significantly associated with outcome were cutaneous histology, low lactate dehydrogenase (LDH), low number of metastatic sites, performance status, first line of treatment and number of combinations administered during the induction phase. Conclusions: Despite the profoundly different baseline patient characteristics, the combination of ipilimumab and nivolumab is as effective in the real-world population as it was in clinical trials, including long-term outcomes. In addition to confirming the significance of baseline prognostic factors, our study reveals that the number of combinations effectively administered may also be correlated with good outcome.

Background: Minimally invasive adrenalectomy has facilitated resection of resistant adrenal metastases. The adrenal gland may function as a sanctuary site for metastatic growth despite systemic therapy. The objective of the study was to assess the outcomes of selective minimally invasive adrenalectomy during immunotherapy., Methods: Candidates included patients with adrenal metastases resistant to systemic therapy who underwent minimally invasive adrenalectomy., Results: There were 15 patients undergoing 16 minimally invasive adrenalectomies. Patients received either immunotherapy or BRAF inhibition prior to surgery. The mean operative time was 130 min with a median length of hospital stay of 2 days. At a median follow up of 24 months, 7 patients have no evidence of disease, 6 patients had progression with eventual mortality, while another patients has stable disease with maintenance therapy. One was lost to follow up., Conclusion: Despite an increase in objective durable responses in metastatic melanoma, there is still some site-specific resistance in isolated areas like the adrenal where early minimally invasive adrenalectomy remains indicated., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest with any of the data submitted in this manuscript., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) mediates objective responses in 30% to 50% of patients with metastatic melanoma according to multiple, small phase 2 trials. Here we report the long-term clinical results, intent-to-treat analysis, predictors of response and toxicity profile in a large patient cohort. A total of 179 refractory melanoma patients were enrolled in the ACT trial. TIL were administered in combination with high-dose bolus interleukin-2 following preconditioning with cyclophosphamide and fludarabine. Patients were followed-up for a median of 7.2 years. A total of 107 (60%) of 179 enrolled patients were treated. The main reason for the drop out of the study was clinical deterioration. Of 103 evaluated patients, 29 patients (28%) achieved an objective response (OR), including complete remission (8%) or partial response (20%). Sixteen pateints exhibited stable disease. Predictors of response were performance status, time of TIL in culture and CD8 frequency in the infusion product. The absolute lymphocyte count 1 and 2 weeks after TIL infusion was the most predictive parameter of response. With a medium follow-up time of 7.2 years, OR patients reached a median overall survival (OS) of 58.45 months and a median progression-free survival (PFS) of 15.43 months, as compared with nonresponders, with 6.73 months OS and 2.60 months PFS. By 6 years, 50% of OR patients were alive and 43% had no documented progression. TIL ACT can yield durable objective responses, even as salvage therapy in highly advanced metastatic melanoma patients., (© 2020 Wiley Periodicals LLC.)

Aim: The selective BRAF and MEK inhibitors (BRAFi+MEKi) have substantially improved the survival of melanoma patients with BRAF V600 mutations. However, BRAFi+MEKi can also cause severe or fatal outcomes. We aimed to identify and compare serious adverse events (sAEs) that are significantly associated with BRAFi+MEKi. Methods: In this pharmacovigilance study, we reviewed FDA Adverse Event Reporting System (FAERS) data in order to detect sAE reporting in patients treated with the combination therapies vemurafenib+cobimetinib (V+C), dabrafenib+trametinib (D+T) and encorafenib+binimetinib (E+B). We evaluated the disproportionate reporting of BRAFi+MEKi-associated sAEs. Significant associations were further analyzed to identify combination-specific safety signals among BRAFi+MEKi. Results: From January 2018 through June 2019, we identified 11,721 sAE reports in patients receiving BRAFi+MEKi. Comparison of BRAFi+MEKi combinations demonstrates that skin toxicities, including Stevens-Johnson syndrome, were disproportionally reported using V+C, with an age-adjusted reporting odds ratio (adj. ROR) of 3.4 (95%CI, 2.9-4.0), whereas fever was most significantly associated with D+T treatment with an adj. ROR of 1.9 (95%CI, 1.5-2.4). Significant associations using E+B treatment include peripheral neuropathies (adj. ROR 2.7; 95%CI, 1.2-6.1) and renal disorders (adj. ROR 4.1; 95%CI, 1.3-12.5). Notably, we found an increase in the proportion of Guillain-Barré syndrome reports (adj. ROR 8.5; 95%CI, 2.1-35.0) in patients administered E+B. Conclusion: BRAFi+MEKi combinations share a similar safety profile attributed to class effects, yet concomitantly, these combinations display distinctive effects that can dramatically impact patients' health. Owing to the limitations of pharmacovigilance studies, some findings warrant further validation. However, the possibility of an increased risk for these events should be considered in patient care.

We study the spatiotemporal correlation of terrorist attacks by al-Qaeda, the Islamic State of Iraq and Syria (ISIS), and local insurgents, in six geographical areas identified via k-means clustering applied to the Global Terrorism Database. All surveyed organizations exhibit near-repeat activity whereby a prior attack increases the likelihood of a subsequent one by the same group within 20 km and on average 4 (al-Qaeda) to 10 (ISIS) weeks. Near-response activity, whereby an attack by a given organization elicits further attacks from a different one, is found to depend on the adversarial, neutral, or collaborative relationship between the two. When in conflict, local insurgents respond quickly to attacks by global terror groups while global terror groups delay their responses to local insurgents, leading to an asymmetric dynamic. When neutral or allied, attacks by one group enhance the response likelihood of the other, regardless of hierarchy. These trends arise consistently in all clusters for which data are available. Government intervention and spillover effects are also discussed; we find no evidence of outbidding. Understanding the regional dynamics of terrorism may be greatly beneficial in policy making and intervention design., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Introduction: Immune checkpoint inhibitors (ICIs) have changed the oncologic landscape in the past few years. Alongside impressive antitumor responses, new novel immune-related adverse events (irAEs) have emerged; pneumonitis is an irAE that can potentially be fatal and necessitates a proper management. No consensus exists regarding steroid treatment duration or drug rechallenge options. Our study describes the clinical and radiological course of melanoma patients diagnosed with immune-related pneumonitis that has recurred because of rechallenge attempt or despite complete treatment discontinuation (unprovoked)., Materials and Methods: The study population was composed of patients with metastatic melanoma who were treated with anti-programmed cell death 1 (PD-1) as monotherapy or in combination with anti-cytotoxic T lymphocyte antigen-4 and who were diagnosed with immune-related pneumonitis. For recurrent cases after clinical and radiological resolution, we explored the differences from cases with no recurrence., Results: Nineteen out of 386 (4.8%) patients treated with ICI were diagnosed with pneumonitis. Median age was 66 years, and 53% were male. Compared with single-agent nivolumab, patients treated with ipilimumab-nivolumab combination presented with an earlier onset (27.5 vs. 10.3 weeks, respectively, p = .015) and had higher grades of severity. After complete resolution, rechallenge was attempted in seven patients; three of them had recurrent pneumonitis. Three other patients experienced recurrent pneumonitis despite complete discontinuation of the drug (unprovoked by rechallenge). The latter were characterized with an earlier onset of the first pneumonitis compared with those who did not experience recurrence (median, 12.4 vs. 26.4 weeks) and a shorter course of steroid treatment at first episode (median, 5.1 vs. 10 weeks). Recurrent cases were generally more severe than the first episode., Conclusion: Unprovoked recurrent pneumonitis is a new, poorly reported entity that requires further investigation. Our observations suggest that cases of pneumonitis that present early in the course of immunotherapy treatment may recur despite treatment discontinuation, thus necessitating closer monitoring and a longer course of steroid treatment., Implications for Practice: This article sheds light on a poorly described immune-related adverse event: recurrent pneumonitis despite complete discontinuation of immunotherapy (unprovoked), in patients with advanced melanoma., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

A-to-I RNA editing, catalyzed by ADAR proteins, is widespread in eukaryotic transcriptomes. Studies showed that, in C. elegans, ADR-2 can actively deaminate dsRNA, whereas ADR-1 cannot. Therefore, we set out to study the effect of each of the ADAR genes on the RNA editing process. We performed comprehensive phenotypic, transcriptomics, proteomics, and RNA binding screens on worms mutated in a single ADAR gene. We found that ADR-1 mutants exhibit more-severe phenotypes than ADR-2, and some of them are a result of non-editing functions of ADR-1. We also show that ADR-1 significantly binds edited genes and regulates mRNA expression, whereas the effect on protein levels is minor. In addition, ADR-1 primarily promotes editing by ADR-2 at the L4 stage of development. Our results suggest that ADR-1 has a significant role in the RNA editing process and in altering editing levels that affect RNA expression; loss of ADR-1 results in severe phenotypes., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Recent data hint at better response to therapy for patients over age 65 years. Patients with metastatic melanoma in their 80's and 90's pose a clinical challenge. We describe a cohort of 144 patients ≥65 years and analyse the efficacy and toxicity of anti-PD-1 therapy in ages 80-100 years compared with ages 65-79 years. Records of metastatic melanoma patients aged 65-100 years treated with anti-PD-1 were collected retrospectively. Baseline parameters, response rate (overall response rate [ORR]), best response, progression-free survival (PFS) and overall survival (OS) and immune-related adverse events were analysed. Cox regression, t test, and chi-square test were used for statistical analysis. Five hundred patients were treated with anti-PD-1 agents between 2013 and 2018.Eighty-two patients were aged 65-79 years (group A, median 71.5 years), and 62 patients were aged 80-100 years (group B, median 84 years, range 80-97 years). Baseline parameters were comparable except for worse PS in group B (p = 0.001). One hundred twenty-four patients were evaluable for analysis of response (76 group A, 48 group B). A trend was noted for higher ORR in the older group with 62.3% for group A and 73.9% for group B (p = 0.09). Complete response was significantly higher in group B versus group A (47.9% versus 20%, p = 0.001). No significant difference was found in PFS or OS between the groups. Toxicity for all patients was similar at 22.8%-25.6% G2-4 adverse events. Elderly patients show enhanced response to anti-PD-1 therapy. Increasing age within the elderly patients group may predict an even better response to therapy and comparable survival in patients of very old age., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: We identify three risk-related behaviors in coping with cyber threats-the exposure to risk a person chooses, use of security features, and responses to security indications. The combinations of behaviors that users choose determine how well they cope with threats and the severity of adverse events they experience., Background: End users' coping with risks is a major factor in cybersecurity. This behavior results from a combination of risk-related behaviors rather than from a single risk-taking tendency., Method: In two experiments, participants played a Tetris-like game, attempting to maximize their gains, while exogenous occasional attacks could diminish earnings. An alerting system provided indications about possible attacks, and participants could take protective actions to limit the losses from attacks., Results: Variables such as the costs of protective actions, reliability of the alerting system, and attack severity affected the three behaviors differently. Also, users dynamically adjusted each of the three risk-related behaviors after gaining experience with the system., Conclusion: The results demonstrate that users' risk taking is the complex combination of three behaviors rather than the expression of a general risk-taking tendency. The use of security features, exposure to risk, and responses to security indications reflect long-term strategy, short-term tactical decisions, and immediate maneuvering in coping with risks in dynamic environments., Application: The results have implications for the analysis of cybersecurity-related decisions and actions as well as for the evaluation and design of systems and targeted interventions in other domains.

Immune-checkpoint inhibitor (ICI)-related diarrhea is attributed to inflammatory colitis, with no other drug-related differential diagnosis. Here, we investigated the occurrence of pancreatic atrophy (PA) in ICI-treated cancer patients and its correlation to exocrine pancreatic insufficiency (EPI). Metastatic melanoma, non-small cell lung carcinoma, and head and neck squamous cell carcinoma patients ( n = 403) treated with anti-PD-1 ( n = 356) or anti-CTLA-4 ( n = 47) were divided into a case group (radiologic evidence of PA); control group matched by age, gender, and previous lines of treatment; and colitis group (ICI-induced colitis). Quantitative pancreatic volumetry was used for calculation of the decrease in pancreatic volume over time (atrophy rate). Thirty-one patients (7.7%) developed PA compared with 41 matched controls ( P = 0.006). Four patients developed EPI, all from the anti-PD-1-treated group, which resolved with oral enzyme supplementation. The atrophy rate did not correlate with EPI ( P = 0.87). EPI-related diarrhea presented at a median of 9 months, whereas the diarrhea of anti-PD-1-induced colitis patients ( n = 22) was presented at a median of 2 months ( P = 0.029). ICI-induced PA is irreversible and can result in EPI. EPI should be suspected in cases of late-onset steroid-resistant diarrhea with features of steatorrhea and treated with oral enzyme supplements., (©2018 American Association for Cancer Research.)

BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are among the cornerstones of metastatic melanoma therapy demonstrating excellent response rates with duration of 7-12 m. Long-term benefit from these agents was reported in patients with normal lactate dehydrogenase (LDH) and less than three disease sites. However, a treatment-dependent marker for long-term efficacy is lacking. Data suggest that immune-related adverse events (irAEs) are associated with clinical benefit in patients treated with immunotherapy and that response to BRAF/MEK therapy may have an underlying immune mechanism. We hypothesised that AEs with an underlying immune mechanism may be associated with a durable response to targeted therapy. We retrospectively identified a cohort of 78 BRAF V600-mutant metastatic melanoma patients treated with BRAFi or BRAFi + MEKi between November 2010 and November 2013. Four treatment-related AEs including vitiligo, uveitis, erythema nodosum and keratitis sicca were defined as irAEs of interest. Retrospective analysis of AEs in relationship to progression-free survival (PFS), disease burden and LDH levels was performed. Median PFS (mPFS) for all patients was 7.5 months with responses ongoing in eight patients as of April 2017. Ten patients were identified with the AEs defined previously. Cox regression analysis revealed a very strong association between those AEs and PFS; mPFS was 42.8 m in patients with at least one AE versus 6.1 m in those without an AE (hazard ratio [HR] 0.22, p = 0.002). This association was independent of LDH levels and disease burden (HR 0.24, p = 0.035). This analysis demonstrates a strong association between immune AEs and durable response to targeted therapy and may provide a treatment-related biomarker to estimate the outcome of therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In recent years, A-to-I RNA modifications performed by the Adenosine Deaminase Acting on RNA (ADAR) protein family were found to be expressed at altered levels in multiple human malignancies. A-to-I RNA editing changes adenosine to inosine on double stranded RNA, thereby changing transcript sequence and structure. Although A-to-I RNA editing have the potential to change essential mRNA transcripts, affecting their corresponding protein structures, most of the human editing sites identified to date reside in non-coding repetitive transcripts such as Alu elements. Therefore, the impact of the hypo- or hyper-editing found in specific cancers remains unknown. Moreover, it is yet unclear whether or not changes in RNA editing and ADAR expression levels facilitate or even drive cancer progression or are just a byproduct of other affected pathways. In both cases, however, the levels of RNA editing and ADAR enzymes can possibly be used as specific biomarkers, as their levels change differently in specific malignancies. More significantly, recent studies suggest that ADAR enzymes can be used to reverse the oncogenic process, suggesting a potential for gene therapies. This review focuses on new findings that suggest that RNA editing by ADARs can affect cancer progression and even formation. We also discuss new possibilities of using ADAR enzymes and RNA editing as cancer biomarkers, indicators of chemotherapeutic drug sensitivity, and even to be themselves potential therapeutic tools., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We analyze the dynamics of repeated interaction of two players in the Prisoner's Dilemma (PD) under various levels of interdependency information and propose an instance-based learning cognitive model (IBL-PD) to explain how cooperation emerges over time. Six hypotheses are tested regarding how a player accounts for an opponent's outcomes: the selfish hypothesis suggests ignoring information about the opponent and utilizing only the player's own outcomes; the extreme fairness hypothesis weighs the player's own and the opponent's outcomes equally; the moderate fairness hypothesis weighs the opponent's outcomes less than the player's own outcomes to various extents; the linear increasing hypothesis increasingly weighs the opponent's outcomes at a constant rate with repeated interactions; the hyperbolic discounting hypothesis increasingly and nonlinearly weighs the opponent's outcomes over time; and the dynamic expectations hypothesis dynamically adjusts the weight a player gives to the opponent's outcomes, according to the gap between the expected and the actual outcomes in each interaction. When players lack explicit feedback about their opponent's choices and outcomes, results are consistent with the selfish hypothesis; however, when this information is made explicit, the best predictions result from the dynamic expectations hypothesis., (Copyright © 2014 Cognitive Science Society, Inc.)

Background: Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR., Methods and Findings: We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set--the Kidney Solid Organ Response Test (kSORT)--was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91-0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88-1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86-0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials., Conclusions: The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary.

Background: Over the years, PTWs' number of accidents have increased dramatically and have accounted for a high percentage of the total traffic fatalities. The majority of those accidents occur in daylight, clear weather, and at light to moderate traffic conditions. The current study included two experiments. The first experiment evaluated the influence of PTW attention conspicuity on the ability of un-alerted viewers to detect it, whereas the second experiment evaluated the PTWs search conspicuity to alerted viewers. The independent variables in both experiments included driving scenarios (urban and inter-urban), PTW rider's outfit (black, white, and reflective) and PTW distance from the viewer., Method: 66 students participated in experiment 1. Every participant was presented with a series of pictures and was asked to report all the vehicle types present in each picture. Experiment 2 included 64 participants and incorporated the same pictures as experiment 1. However, in this experiment the participants were instructed to search the pictures for a PTW and to report its presence or absence as soon as they reach a decision., Results: In experiment 1 the detection of a PTW depended on the interaction between its distance from the viewer, the driving scenario and PTW rider's outfit. For an un-alerted viewer when the PTW was distant the different outfit conditions affected its' attention conspicuity. In urban roads, where the background surrounding the PTW was more complex and multi-colored, the reflective and white outfits increased its attention conspicuity compared to the black outfit condition. In contrast, in inter-urban roads, where the background was solely a bright sky, the black outfit provided an advantage for the PTW detectability. In experiment 2, the average PTW detection rate of the alerted viewers was very high and the average reaction time to identify the presence of a PTW was the shortest in the inter-urban environment. Similar to the results of experiment 1, in urban environments the reflective and white clothing provided an advantage to the detection of the PTW, while in the inter-urban environment the black outfit presented an advantage. Comparing the results of the two experiments revealed that at the farthest distance, the increased awareness in the search conspicuity detection rates were three times higher than in the attention conspicuity., Conclusions: The conspicuity of a PTW can be increased by using an appropriate rider's outfit that distinguishes him/her from the background scenery. Thus, PTW riders can actively increase their conspicuity by taking into account the driving route (crowded urban/inter urban), eventually increasing the probability of being detected by the other road users. In addition, increasing the alertness and expectancy of drivers to the presence of PTWs can increase their search conspicuity., (2010 Elsevier Ltd. All rights reserved.)

Surface plasmon resonance (SPR) is a widely employed technique for studying protein-protein interactions. Here, we describe a method for the analysis of single-stranded DNA binding protein (SSB)-heterologous protein interactions by SPR. This method avoids several pitfalls often associated with SPR, particularly difficulties in immobilizing the protein while still allowing for facile regeneration of the sensor chip surface for subsequent experiments. Essentially, the method entails immobilizing a biotinylated single-stranded DNA oligo onto the chip surface, which is then bound by SSB prior to analyte addition to the SSB-coated chip. This allows for rapid qualitative and detailed quantitative analysis of both equilibrium and kinetic parameters of the SSB-protein interaction.

Drug metabolism/disposition and transporter genes may influence predisposition or prognosis of AML (acute myeloid leukemia) patients. We analyzed polymorphisms in 3 transporters and 4 drug metabolism genes in 293 Israeli individuals (112 AML patients and 181 controls). We analyzed: ABCC3 (MRP3) C-211T; ABCG2 (BCRP) C421A; CNT1 (SLC28A1) G565A and NAT1, NAT2, and GSTT1 and GSTM1 null alleles for influence on predisposition, as well as treatment response and survival. We found that the ABCC3 C-211T polymorphism and GSTM1 null genotype have adverse prognostic significance in AML. None of the other polymorphisms studied were found to influence either predisposition or prognosis in Israeli AML patients.

alpha-Thalassemia is among the world's most common single gene disorders, which is most prevalent in the malaria belt. This geographic distribution has been attributed to a selective advantage of heterozygotes against this disease. Unexpectedly, we have found a high frequency of heterozygosity for deletional alpha-thalassemia (-alpha3.7) in Ashkenazi Jews (carrier frequency of 7.9%, allele frequency of 0.04). This population has resided in temperate climates for many centuries and was therefore not subjected to malarial selection pressure. In comparison, heterozygosity for beta-thalassemia, which is highly subject to malarial selection pressure, is very low (estimated <0.1%) in this group. It is possible that founder effect and genetic drift have contributed to the high frequency of deletional alpha-thalassemia in Ashkenazim, as may occur in closed populations. Alternatively, we hypothesize that positive selection pressure for an as yet unknown linked allele on chromosome 16 may be a significant factor leading to this high frequency.

[reaction: see text] Treatment of primary alkyl triflates or iodides with the potassium salt of diethyl (alpha-fluoro-alpha-phenylsulfonylmethyl)phosphonate yields (alpha-fluoro-alpha-phenylsulfonylalkyl)phosphonates. These can be cleanly desulfonated, in a matter of minutes, with Na(Hg) in MeOH/THF/NaH(2)PO(4). This two-step procedure complements previously reported triflate displacement approaches to alpha-nonfluorinated and alpha,alpha-difluorinated phosphonates.