Long lifetime of bialkali photocathodes operating in high gradient superconducting radio frequency gun.

High brightness, high charge electron beams are critical for a number of advanced accelerator applications. The initial emittance of the electron beam, which is determined by the mean transverse energy (MTE) and laser spot size, is one of the most important parameters determining the beam quality. The bialkali photocathodes illuminated by a visible laser have the advantages of high quantum efficiency (QE) and low MTE. Furthermore, Superconducting Radio Frequency (SRF) guns can operate in the continuous wave (CW) mode at high accelerating gradients, e.g. with significant reduction of the laser spot size at the photocathode. Combining the bialkali photocathode with the SRF gun enables generation of high charge, high brightness, and possibly high average current electron beams. However, integrating the high QE semiconductor photocathode into the SRF guns has been challenging. In this article, we report on the development of bialkali photocathodes for successful operation in the SRF gun with months-long lifetime while delivering CW beams with nano-coulomb charge per bunch. This achievement opens a new era for high charge, high brightness CW electron beams.

High-Brightness Continuous-Wave Electron Beams from Superconducting Radio-Frequency Photoemission Gun.

Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation of monochromatic x-ray free electron lasers, high-brightness hadron beams, or a new generation of microchip production. In this Letter we report on the record-performing superconducting rf electron gun with CsK_{2}Sb photocathode. The gun is generating high charge electron bunches (up to 10 nC/bunch) and low transverse emittances, while operating for months with a single photocathode. This achievement opens a new era in generating high-power beams with a very high average brightness.

Experimental Demonstration of Hadron Beam Cooling Using Radio-Frequency Accelerated Electron Bunches.

Cooling of beams of gold ions using electron bunches accelerated with radio-frequency systems was recently experimentally demonstrated in the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. Such an approach is new and opens the possibility of using this technique at higher energies than possible with electrostatic acceleration of electron beams. The challenges of this approach include generation of electron beams suitable for cooling, delivery of electron bunches of the required quality to the cooling sections without degradation of beam angular divergence and energy spread, achieving the required small angles between electron and ion trajectories in the cooling sections, precise velocity matching between the two beams, high-current operation of the electron accelerator, as well as several physics effects related to bunched-beam cooling. Here we report on the first demonstration of cooling hadron beams using this new approach.

Multi-atmosphere picosecond CO2 amplifier optically pumped at 4.3 µm.

The possibility of the amplification of picosecond 10 µm pulses to gigawatt powers in an optically pumped 20 atmosphere CO2 laser is shown using numerical simulations. Multi-millijoule 4.3 µm pulses generated by a tunable Fe:ZnSe laser are considered for pumping.

Immunoglobulin free light chains in saliva: a potential marker for disease activity in multiple sclerosis.

A new procedure was developed and applied to study immunoglobulin free light chains (FLC) in saliva of healthy subjects and patients with multiple sclerosis (MS). The procedure was based on a Western blot analysis for detection and semiquantitative evaluation of monomeric and dimeric FLCs. The FLC indices accounting for the total FLC levels and for the monomer/dimer ratios of κ and λ FLC were calculated, and the cut-off values of the FLC indices were determined to distinguish healthy state from MS disease. The obtained FLC index values were statistically different in the saliva of three groups: active MS patients, MS patients in remission and healthy subjects groups. Our FLC monomer-dimer analysis allowed differentiation between healthy state and active MS with specificity of 100% and a sensitivity of 88·5%. The developed technique may serve as a new non-invasive complementary tool to evaluate the disease state by differentiating active MS from remission with sensitivity of 89% and specificity of 80%.

Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors.

BACKGROUND: While patient-derived xenografts (PDXs) offer a powerful modality for translational cancer research, a precise evaluation of how accurately patient responses correlate with matching PDXs in a large, heterogeneous population is needed for assessing the utility of this platform for preclinical drug-testing and personalized patient cancer treatment. PATIENTS AND METHODS: Tumors obtained from surgical or biopsy procedures from 237 cancer patients with a variety of solid tumors were implanted into immunodeficient mice and whole-exome sequencing was carried out. For 92 patients, responses to anticancer therapies were compared with that of their corresponding PDX models. RESULTS: We compared whole-exome sequencing of 237 PDX models with equivalent information in The Cancer Genome Atlas database, demonstrating that tumorgrafts faithfully conserve genetic patterns of the primary tumors. We next screened PDXs established for 92 patients with various solid cancers against the same 129 treatments that were administered clinically and correlated patient outcomes with the responses in corresponding models. Our analysis demonstrates that PDXs accurately replicate patients' clinical outcomes, even as patients undergo several additional cycles of therapy over time, indicating the capacity of these models to correctly guide an oncologist to treatments that are most likely to be of clinical benefit. CONCLUSIONS: Integration of PDX models as a preclinical platform for assessment of drug efficacy may allow a higher success-rate in critical end points of clinical benefit.

Association between specimen length and diagnostic yield of temporal artery biopsy.

OBJECTIVES: Temporal artery biopsy (TAB) is performed in patients suspected of giant cell arteritis (GCA). Inadequate TAB specimen length is considered a possible explanation for a negative biopsy in patients with GCA. We investigated the association between specimen length and diagnostic yield of TAB. METHOD: We conducted a retrospective analysis of 240 patients who underwent TAB in a single hospital between 2000 and 2015. Patients were diagnosed with GCA based on positive TAB or, when TAB was negative, on clinical grounds that fulfilled the American College of Rheumatology (ACR) 1990 criteria. Baseline clinical and laboratory features and TAB length were obtained from medical records. Among patients diagnosed with GCA, the rate of TAB positivity was calculated according to biopsy length (< 5, 5-9, 10-14, and ≥ 20 mm). RESULTS: Out of 240 patients, 88 were diagnosed with GCA: 62 had a positive TAB and 26 were diagnosed based on clinical grounds despite a negative TAB. Among those who were diagnosed with GCA, the length of the TAB specimen was similar in those with a positive and a negative TAB (1.13 ± 1.68 mm vs. 1.15 ± 0.61 mm, respectively, p = 0.928). The TAB positivity rate was similar among all ranges of biopsy length [< 5 mm: 7/10 (70%); 5-9 mm: 22/31 (71%); 10-14 mm: 11/16 (69%); 15-19 mm: 11/16 (69%); ≥ 20 mm: 11/15 (73%, p = ns] and was similar to the overall biopsy positivity rate. CONCLUSIONS: Specimen length is not associated with diagnostic yield of TAB.

Design of a high-bunch-charge 112-MHz superconducting RF photoemission electron source.

High-bunch-charge photoemission electron-sources operating in a continuous wave (CW) mode are required for many advanced applications of particle accelerators, such as electron coolers for hadron beams, electron-ion colliders, and free-electron lasers. Superconducting RF (SRF) has several advantages over other electron-gun technologies in CW mode as it offers higher acceleration rate and potentially can generate higher bunch charges and average beam currents. A 112 MHz SRF electron photoinjector (gun) was developed at Brookhaven National Laboratory to produce high-brightness and high-bunch-charge bunches for the coherent electron cooling proof-of-principle experiment. The gun utilizes a quarter-wave resonator geometry for assuring beam dynamics and uses high quantum efficiency multi-alkali photocathodes for generating electrons.

Is temporal artery biopsy essential in all cases of suspected giant cell arteritis?

OBJECTIVES: Temporal artery biopsy (TAB) is performed in cases of suspected giant cell arteritis (GCA), and is the gold-standard for diagnosis of the disease. Current American College of Rheumatology (ACR) classification criteria may aid in the diagnosis of GCA. We aimed to assess whether TAB is essential in all cases of suspected GCA, or whether ACR criteria can replace the need for this procedure in some cases. METHODS: Retrospective analysis of 216 patients who underwent TAB in a single hospital between 2000 and 2013. Pre-TAB and post-TAB ACR criteria were calculated. Sensitivity and specificity of ACR criteria for the diagnosis of GCA were assessed. RESULTS: Overall, 55 patients had histological evidence of GCA.Out of 161 patients with negative TAB findings, 34 were diagnosed with GCA, and 127 were not diagnosed with GCA. Sensitivity of TAB for the diagnosis of GCA was 61.7%. Sensitivity and specificity of ACR criteria for diagnosis of GCA before performing TAB were 68.5% and 58%, respectively. Sensitivity and specificity of ACR criteria after performing TAB biopsy were 89.8% and 64.5%, respectively. CONCLUSIONS: Temporal artery biopsy should be performed in the majority of patients with suspected GCA, and may be obviated only in patients with a pre-TAB ACR score of ≤ 1. In all other cases, when GCA is suspected, ACR criteria should not be a substitute to TAB, as they are not highly specific.

The external Q factor of a dual-feed coupling for superconducting radio frequency cavities: theoretical and experimental studies.

We propose a theoretical model based on network analysis to study the external quality factor (Q factor) of dual-feed coupling for superconducting radio-frequency (SRF) cavities. Specifically, we apply our model to the dual-feed 704 MHz half-cell SRF gun for Brookhaven National Laboratory's prototype Energy Recovery Linac (ERL). The calculations show that the external Q factor of this dual-feed system is adjustable from 10(4) to 10(9) provided that the adjustment range of a phase shifter covers 0°-360°. With a period of 360°, the external Q factor of the coupling system changes periodically with the phase difference between the two coupling arms. When the RF phase of both coupling arms is adjusted simultaneously in the same direction, the external Q factor of the system also changes periodically, but with a period of 180°.

T helper 17 polarization in familial Mediterranean fever.

Autoinflammatory attacks in familial Mediterranean fever (FMF) are accompanied by elevated levels of interleukin-6 (IL-6), and are controllable by IL-1-targeting drugs. In combination, IL-6 and IL-1 are known to be potent inducers of T helper (Th) 17 cells development. Therefore, we studied the Th17 population size, and activation potential, of FMF patients. Based on the relative mRNA expression of the Th1, Th2, Treg and Th17 transcription factors T-bet, GATA3, FOXP3 and retinoic acid-related orphan receptor γT (RORγT), respectively, the Th17 population in peripheral blood mononuclear cells (PBMCs) of healthy subjects was estimated at 2.5% of the entire Th population and 4.4% in FMF patients in remission (n=6 for each group, P=0.03). IL-17 secretion after universal stimulation of the T-cell receptor in PBMCs culture was twice higher in cultures of patients with frequent attacks (n=18) than in those of patients with infrequent attacks (n=10, 1124±266 vs 615±196 pg ml(-1), P=0.009). IL-17 secretion correlated well with IL17A mRNA level. Part of the increased secretion was related to the deleterious, MEFV p.M694V homozygous genotype (n=19, 1.5-fold, P=0.03). Almost all IL-17 producer cells were CD4-positive (CD4(+)IL-17(+)). In conclusion, frequent attacks and the deleterious FMF genotype appear to drive FMF patients to a heightened Th17 response.

Exertional muscle pain in familial Mediterranean fever patients evaluated by MRI and 31P magnetic resonance spectroscopy.

AIM: To evaluate the effect of physical activity on the structural, morphological, and metabolic characteristics of the gastrocnemius muscle in familial Mediterranean fever (FMF) patients, utilizing quantitative (31)P magnetic resonance spectroscopy (MRS), in order to elucidate the mechanism of their exertional leg pain. MATERIALS AND METHODS: Eleven FMF patients suffering from exertional leg pain (eight male, three female; mean age 33 years) and six healthy individuals (three male, three female; mean age 39 years) constituted the control group. All of the participants underwent magnetic resonance imaging (MRI) and non-selective (31)P MRS (3 T) of the leg muscles before and after graded exercise on a treadmill. Phosphocreatine (PCr):inorganic phosphate (Pi), PCr:adenosine triphosphate (ATP) ratios and the intracellular pH of the leg muscles were measured using (31)P MRS. RESULTS: For both groups, normal muscle mass with no signal alterations was observed on the MRI images after exercise. The normal range of pre- and post- exercise MRS muscle parameters was observed in both groups. However, the intracellular pH post-exercise, was significantly higher (less acidic) in the FMF group compared to the control group [pH (FMF) = 7.03 ± 0.02; pH (control) 7.00 ± 0.02; p < 0.0006]. CONCLUSIONS: The finding of a less prominent, post-exercise acidification of the gastrocnemius muscle in this FMF patient group suggests a forme fruste of glycogenosis. This preliminary observation should be further investigated in a future, larger-scale study.

Exertional leg pain as a manifestation of occult spondyloarthropathy in familial Mediterranean fever: an MRI evaluation.

OBJECTIVES: Familial Mediterranean fever (FMF) is characterized by recurrent episodes of fever, peritonitis, arthritis, and pleuritis, caused by neutrophil-induced sterile serositis. Another clinical manifestation in patients with FMF is exertional leg and ankle pain that appears after minor exercise, for which the underlying mechanism is obscure. The purpose of the current study was to feature distal leg changes in FMF patients complaining of exertional leg pain, using magnetic resonance imaging (MRI). METHODS: Eleven patients with FMF who suffer from exertional leg pain (eight males, three females; mean age 33 years) and six unaffected controls (three males, three females; mean age 39 years) underwent MRI (3 T) of the ankle, including conventional T1 and T2 with fat saturation sequences, before and after graded exercise on a treadmill. Clinical and genetic data and sacroiliac radiographs were obtained. RESULTS: Ten patients (91%) with FMF but none of the control group had signs compatible with enthesitis of the Achilles tendon, long plantar ligament, or the plantar fascia (including enthesophytes, erosions, and bone marrow oedema). Nine patients (80%) had radiographic signs of sacroiliitis on the pelvic radiograph. CONCLUSIONS: Exertional leg pain in FMF patients, shown to be associated with signs of enthesopathy on imaging, may be included within the spectrum of spondyloarthropathy.

'Silent' carriage of two familial Mediterranean fever gene mutations in large families with only a single identified patient.

The presence of two mutations in the familial Mediterranean fever gene, without overt familial Mediterranean fever (FMF), designated as phenotype III, predisposes to developing 'silent' AA amyloidosis, recognized as phenotype II, due to the absence of medical supervision and colchicine prophylaxis. We sought to determine the prevalence of phenotype III in large families with only one subject affected with FMF, in order to assess the population at risk for transformation to phenotype II. A total of seven large families were recruited for the study. Siblings were screened for MEFV mutations and underwent a clinical interview to assess for unrecognized FMF manifestations. Phenotype III, most commonly associated with a V726A/E148Q genotype, was detected in 10% of siblings of index cases from informative families, corresponding to a 10-fold increase in comparison to the expected rate in the general population (p < 0.01). Unnoticed 'FMF-like' manifestations were detected among two siblings in the five families in which the index case was heterozygous, but in none of the siblings of the homozygous index cases. The enrichment for phenotype III and detection of occult FMF in large families, in which only a single member is afflicted with FMF, mandates routine clinical evaluation and genetic screening of siblings.

Inverse free electron lasers and laser wakefield acceleration driven by CO2 lasers.

The staged electron laser acceleration (STELLA) experiment demonstrated staging between two laser-driven devices, high trapping efficiency of microbunches within the accelerating field and narrow energy spread during laser acceleration. These are important for practical laser-driven accelerators. STELLA used inverse free electron lasers, which were chosen primarily for convenience. Nevertheless, the STELLA approach can be applied to other laser acceleration methods, in particular, laser-driven plasma accelerators. STELLA is now conducting experiments on laser wakefield acceleration (LWFA). Two novel LWFA approaches are being investigated. In the first one, called pseudo-resonant LWFA, a laser pulse enters a low-density plasma where nonlinear laser/plasma interactions cause the laser pulse shape to steepen, thereby creating strong wakefields. A witness e-beam pulse probes the wakefields. The second one, called seeded self-modulated LWFA, involves sending a seed e-beam pulse into the plasma to initiate wakefield formation. These wakefields are amplified by a laser pulse following shortly after the seed pulse. A second e-beam pulse (witness) follows the seed pulse to probe the wakefields. These LWFA experiments will also be the first ones driven by a CO(2) laser beam.

Observation of anomalously large spectral bandwidth in a high-gain self-amplified spontaneous emission free-electron laser.

Observation of ultrawide bandwidth, up to 15% full-width, high-gain operation of a self-amplified spontaneous emission free-election laser (SASE FEL) is reported. This type of lasing is obtained with a strongly chirped beam (deltaE/E approximately 1.7%) emitted from the accelerator. Because of nonlinear pulse compression during transport, a short, high current bunch with strong mismatch errors is injected into the undulator, giving high FEL gain. Start-to-end simulations reproduce key features of the measurements and provide insight into mechanisms, such as angular spread in emitted photon and electron trajectory distributions, which yield novel features in the radiation spectrum.

Demonstration of high-trapping efficiency and narrow energy spread in a laser-driven accelerator.

Laser-driven electron accelerators (laser linacs) offer the potential for enabling much more economical and compact devices. However, the development of practical and efficient laser linacs requires accelerating a large ensemble of electrons together ("trapping") while keeping their energy spread small. This has never been realized before for any laser acceleration system. We present here the first demonstration of high-trapping efficiency and narrow energy spread via laser acceleration. Trapping efficiencies of up to 80% and energy spreads down to 0.36% (1 sigma) were demonstrated.

Cohesive acceleration and focusing of relativistic electrons in overdense plasma.

We describe our studies of the generation of plasma wake fields by a relativistic electron bunch and of phasing between the longitudinal and transverse fields in the wake. The leading edge of the electron bunch excites a high-amplitude plasma wake inside the overdense plasma column, and the acceleration and focusing wake fields are probed by the bunch tail. By monitoring the dependence of the acceleration upon the plasma's density, we approached the beam-matching condition and achieved an energy gain of 0.6 MeV over the 17 mm plasma length, corresponding to an average acceleration gradient of 35 MeV/m. Wake-induced modulation in energy and angular divergence of the electron bunch are mapped within a wide range of plasma density. We confirm a theoretical prediction about the phase offset between the accelerating and focusing components of plasma wake.

Properties of the ultrashort gain length, self-amplified spontaneous emission free-electron laser in the linear regime and saturation.

VISA (Visible to Infrared SASE Amplifier) is a high-gain self-amplified spontaneous emission (SASE) free-electron laser (FEL), which achieved saturation at 840 nm within a single-pass 4-m undulator. The experiment was performed at the Accelerator Test Facility at BNL, using a high brightness 70-MeV electron beam. A gain length shorter than 18 cm has been obtained, yielding a total gain of 2 x 10(8) at saturation. The FEL performance, including the spectral, angular, and statistical properties of SASE radiation, has been characterized for different electron beam conditions. Results are compared to the three-dimensional SASE FEL theory and start-to-end numerical simulations of the entire injector, transport, and FEL systems. An agreement between simulations and experimental results has been obtained at an unprecedented level of detail.

Surface-roughness wakefield measurements at brookhaven accelerator test facility.

An experiment has been carried out at the Brookhaven Accelerator Test Facility to investigate the effect of a surface-roughness wakefield in narrow beam tubes with artificially created bumps. The measurements show that the synchronous modes decay significantly due to the randomization of the roughness pattern. It is pointed out that this decay mechanism has not been investigated in the previous experiment at DESY and the investigators' conclusion does not apply for surface-roughness wakefields in real surfaces.