Tunable Electron Multibunch Production in Plasma Wakefield Accelerators

Synchronized, independently tunable and focused $\mu$J-class laser pulses are used to release multiple electron populations via photo-ionization inside an electron-beam driven plasma wave. By varying the laser foci in the laboratory frame and the position of the underdense photocathodes in the co-moving frame, the delays between the produced bunches and their energies are adjusted. The resulting multibunches have ultra-high quality and brightness, allowing for hitherto impossible bunch configurations such as spatially overlapping bunch populations with strictly separated energies, which opens up a new regime for light sources such as free-electron-lasers

Shear-Wave Elastography Assessments of Quadriceps Stiffness Changes prior to, during and after Prolonged Exercise: A Longitudinal Study during an Extreme Mountain Ultra-Marathon.

In sports medicine, there is increasing interest in quantifying the elastic properties of skeletal muscle, especially during extreme muscular stimulation, to improve our understanding of the impact of alterations in skeletal muscle stiffness on resulting pain or injuries, as well as the mechanisms underlying the relationships between these parameters. Our main objective was to determine whether real-time shear-wave elastography (SWE) can monitor changes in quadriceps muscle elasticity during an extreme mountain ultra-marathon, a powerful mechanical stress model. Our study involved 50 volunteers participating in an extreme mountain marathon (distance: 330 km, elevation: +24,000 m). Quantitative SWE velocity and shear modulus measurements were performed in most superficial quadriceps muscle heads at the following 4 time points: before the race, halfway through the race, upon finishing the race and after recovery (+48 h). Blood biomarker levels were also measured. A significant decrease in the quadriceps shear modulus was observed upon finishing the race (3.31±0.61 kPa) (p<0.001) compared to baseline (3.56±0.63 kPa), followed by a partial recovery +48 h after the race (3.45±0.6 kPa) (p = 0.002) across all muscle heads, as well as for each of the following three muscle heads: the rectus femoris (p = 0.003), the vastus medialis (p = 0.033) and the vastus lateralis (p = 0.001). Our study is the first to assess changes in muscle stiffness during prolonged extreme physical endurance exercises based on shear modulus measurements using non-invasive SWE. We concluded that decreases in stiffness, which may have resulted from quadriceps overuse in the setting of supra-physiological stress caused by the extreme distance and unique elevation of the race, may have been responsible for the development of inflammation and muscle swelling. SWE may hence represent a promising tool for monitoring physiologic or pathological variations in muscle stiffness and may be useful for diagnosing and monitoring muscle changes

Autosomal recessive and sporadic non syndromic hearing loss and the incidence of Cx26 mutations in a province of Iran

Despite the enormous heterogeneity of genetic hearing loss, mutations in the GJB2 (connexin 26) gene located on "DFNB1" locus (13q12) account for up to 50 of cases of autosomal recessive non-syndromic hearing loss (ARNSHL) in some populations. This study describes the analysis of 100 autosomal recessive and sporadic nonsyndromic hearing loss individuals from 79 families each having at least one deaf child in Chehar Mahal va Bakhtiari province in west of Iran. We have investigated the prevalence of the connexin 26 gene mutations using nested PCR strategy to screen the predominant 35delG mutation and subsequent direct sequencing to detect other Cx26 mutations. Seven different genetic variants were detected from which one novel variant was including 363delC. The 35delG was the most common mutation found in 5 of 79 families (6.3). Cx26 related deafness mutations (35delG,V27I; E114G) and R127H) were found in 12 of 158 chromosomes studied (7.8%). We conclude that the association of Cx26 mutations with deafness in Chehar Mahal va Bakhtiari province is low and looks like most other populations of Iran

From Forced to Voluntary Participation: The History of Biomedical Human Experimentation in the United States after the Second World War

For as long as medicine and medical practices have been around, so has the need for testing treatments in or procedures on the human body. Over the course of history, however, the nature, structure, and prominence of human biomedical experimentation has changed drastically both on an international and national level. My thesis focuses on revealing the driving forces behind these changes in administrative, legal and social factors related to human experimentation in an effort to connect the dots from the manipulative, forceful and unethical experimentation of early medical practitioners to the safe, voluntary and highly regulated experimentation characteristic of clinical research today. Although human biomedical experimentation spans many cultures, countries, and time frames, my research focuses on the history of experimentation in the United States from the mid-twentieth century until present day, while still framing the topic in a larger global context. I have chosen this time period because it captures an immense period of change and I have chosen to focus on just one country since regulations and cultural shifts related to this topic often occur at a national level. Through my research, I have found that throughout the twentieth century, major cases of unethical human experimentation have sparked periods of public outrage, increased public awareness of ethical issues, and consequently have led to an increase in regulations and an increase in regulatory bodies governing human biomedical experimentation. Such changes have created a much safer system of testing biomedical products or procedures on human subjects in the United States

Hot spots and dark current in advanced plasma wakefield accelerators

Dark current can spoil witness bunch beam quality and acceleration efficiency in particle beam-driven plasma wakefield accelerators. In advanced schemes, hot spots generated by the drive beam or the wakefield can release electrons from higher ionization threshold levels in the plasma media. These electrons may be trapped inside the plasma wake and will then accumulate dark current, which is generally detrimental for a clear and unspoiled plasma acceleration process. Strategies for generating clean and robust, dark current free plasma wake cavities are devised and analyzed, and crucial aspects for experimental realization of such optimized scenarios are discussed

Molecular detection of prostate specific antigen in patients with prostate cancer or benign prostate hyperplasia the first investigation from Iran

Prostate cancer is the second common form of cancer in men. Detection of circulating Prostate Specific Antigen (PSA) transcripts has effectively been used for early diagnosis of prostate cancer cells. This investigation employed a reverse transcriptase polymerase chain reaction (RT-PCR) technique to distinguish the patients with either localized or metastatic prostate cancer (CaP) vs. Benign Prostate Hyperplasia (BPH) and control subjects, as compared with clinical and pathological records. With reservation of ethical issues, blood samples were collected from 60 cases. Based on pathological and clinical findings, 25 patients (20 with localized cancer, 5 with metastatic), 22 with BPH, and 13 healthy (including 3 females) subjects as negative controls, were selected from Shariati, Mehrad, Sina,, Khatam and Atie Hospitals in Tehran, Iran. RT-PCR for a 260 bp PSA transcript was then performed. Clinical and pathological records were used for the assessment and comparison of PSA RT-PCR results. None of the control subjects and BPH (with 7 exceptions) were found positive by RT-PCR (Relative specificity= 72.7). In patients with prostate cancer, 21 out of 25 were found PSA positive (Relative sensitivity= 83.4) and the remaining 3 have been shown to be PSA negative (Positive predictive value= 83.4). All of 5 metastatic patients (100) revealed PSA positive results. Our data reflects the clinical relevance and significance of RT-PCR results as assessed with clinical and pathological examinations. PSA RT-PCR might be used as a powerful means for diagnosis, even when either pathological or clinical findings are negative, and could be employed for further molecular epidemiology surveys

Alterations in skeletal muscle health and biomechanical properties in patients with early rheumatoid arthritis: an exploratory cross-sectional study

BackgroundSkeletal muscle disease in patients with early-stage rheumatoid arthritis (RA) is understudied. The objective of this study was to identify whether patients with early RA (symptoms <6 months) have impaired skeletal muscle health.MethodsParticipants with early RA (n = 10) and age-, sex-, and BMI-matched healthy controls (n = 10) underwent cross-sectional clinical, physiological, and muscle biomechanical property assessments. Upper and lower extremity muscles underwent in vivo passive biomechanical property—tone, stiffness, and elasticity—assessments via myotonometry (MyotonPro®). In vitro muscle force production and stiffness were assessed using 3D bioengineered myobundles derived from myoblasts obtained from vastus lateralis muscle biopsies.ResultsDespite similar muscle mass and self-reported physical activity behaviors for patients with early RA and healthy controls, patients with early RA had poorer self-reported physical function, self-reported physical health, and right-hand grip strength (p < 0.05 for all). Early RA muscle tone and stiffness were lower than in controls (p < 0.05) and had an inverse association with prednisone use (rho = −0.72, p = 0.02). While 3D bioengineered myobundle force production and passive stiffness were similar to controls, early RA myobundle stiffness correlated with swollen joint count (rho = −0.67, p = 0.04).ConclusionIn this exploratory study, patients with early RA exhibited multiple skeletal muscle deficits across clinical, physiologic, and biomechanical domains compared to controls with similar muscle mass and physical activity. In vivo and in vitro skeletal muscle biomechanical assessments may be useful to identify these deficits to better understand and improve RA muscle health

Manipulation and wakefield effects on multi-pulse driver beams in PWFA injector stages

Particle-driven plasma wakefield acceleration (PWFA) exploits the intense wakefields excited in a plasma by a high-brightness driver beam in order to accelerate a trailing, properly delayed witness electron beam. Such a configuration offers notable advantages in achieving very large accelerating gradients that are suitable for applications in particle colliders and photon production. Moreover, the amplitude of the accelerating fields can be enhanced by resonantly exciting the plasma using a multi-pulse driver beam with a proper time structure. Before the injection into the plasma stage, the pulsed electron beam, conventionally termed the comb beam, is usually produced and pre-accelerated in a radio-frequency (RF) linear accelerator (linac). In this pape, we discuss challenging aspects of the dynamics that comb beams encounter in the RF injector stage preceding the plasma. In particular, the examples we analyze focus on the use of velocity bunching to manipulate the time structure of the beam and the impact of dipole short-range wakefields on the transverse emittances. Indeed, both processes crucially affect the phase space distribution and its quality, which are determinant features for an efficient acceleration in the plasma. In addition, the analyses we present are performed with the custom tracking code MILES, which utilizes semi-analytical models for a simplified evaluation of wakefield effects in the presence of space charge force

All-optical density downramp injection in electron-driven plasma wakefield accelerators

Injection of well-defined, high-quality electron populations into plasma waves is a key challenge of plasma wakefield accelerators. Here, we report on the first experimental demonstration of plasma density downramp injection in an electron-driven plasma wakefield accelerator, which can be controlled and tuned in all-optical fashion by mJ-level laser pulses. The laser pulse is directed across the path of the plasma wave before its arrival, where it generates a local plasma density spike in addition to the background plasma by tunnelling ionization of a high ionization threshold gas component. This density spike distorts the plasma wave during the density downramp, causing plasma electrons to be injected into the plasma wave. By tuning the laser pulse energy and shape, highly flexible plasma density spike profiles can be designed, enabling dark current free, versatile production of high-quality electron beams. This in turn permits creation of unique injected beam configurations such as counter-oscillating twin beamlets

Plasma-photonic spatiotemporal synchronization of relativistic electron and laser beams

Modern particle accelerators and their applications increasingly rely on precisely coordinated interactions of intense charged particle and laser beams. Femtosecond-scale synchronization alongside micrometre-scale spatial precision are essential e.g. for pump-probe experiments, seeding and diagnostics of advanced light sources and for plasma-based accelerators. State-of-the-art temporal or spatial diagnostics typically operate with low-intensity beams to avoid material damage at high intensity. As such, we present a plasma-based approach, which allows measurement of both temporal and spatial overlap of high-intensity beams directly at their interaction point. It exploits amplification of plasma afterglow arising from the passage of an electron beam through a laser-generated plasma filament. The corresponding photon yield carries the spatiotemporal signature of the femtosecond-scale dynamics, yet can be observed as a visible light signal on microsecond-millimetre scales