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Particle accelerators and storage rings have been transformative instruments of discovery, and, for many applications, innovations in particle-beam cooling have been a principal driver of that success1. Stochastic cooling (SC), one of the most important conceptual and technological advances in this area2-6, cools a beam through granular sampling and correction of its phase-space structure, thus bearing resemblance to a 'Maxwell's demon'. The extension of SC from the microwave regime up to optical frequencies and bandwidths has long been pursued, as it could increase the achievable cooling rates by three to four orders of magnitude and provide a powerful tool for future accelerators. First proposed nearly 30 years ago, optical stochastic cooling (OSC) replaces the conventional microwave elements of SC with optical-frequency analogues and is, in principle, compatible with any species of charged-particle beam7,8. Here we describe a demonstration of OSC in a proof-of-principle experiment at the Fermi National Accelerator Laboratory's Integrable Optics Test Accelerator9,10. The experiment used 100-MeV electrons and a non-amplified configuration of OSC with a radiation wavelength of 950 nm, and achieved strong, simultaneous cooling of the beam in all degrees of freedom. This realization of SC at optical frequencies serves as a foundation for more advanced experiments with high-gain optical amplification, and advances opportunities for future operational OSC systems with potential benefit to a broad user community in the accelerator-based sciences.

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We present modeling and measurements of flattop amplification of a laser pulse train in a diode pumped Nd:YLF system. We establish a theoretical model, accounting for the transverse Gaussian shape of an amplified laser beam, in order to explain remaining slopes in the pulse train energy. The influence of the transverse Gaussian shape on the train's flatness has been experimentally verified. Based on the model we are able to increase the total amplification of a long train of infrared seed beam in the drive laser system at the Fermilab Accelerator Science and Technology facility. The single-pass amplifier improvements resulted in a gain of ∼7 with flat output pulse train for up to 1000 seed pulses.

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Mismatches between skin pigmentation and modern lifestyle continue to challenge our naked skin. One of our responses to these challenges is the development and use of sunscreens. The management of sunscreens has to balance their protective effect against erythema, photocarcinogenesis and photoageing owing to the potential toxicity of the ultraviolet (UV) filters for humans and the environment. The protection against UV radiation offered by sunscreens was recently standardized in the European Union (EU) based on international harmonization of measurement techniques. Four different categories of sun protection have been implemented along with recommendations on how to use sunscreen products in order to obtain the labelled protection. The UV filters in sunscreens have long been authorized for use by the EU authority on the basis of data from studies on acute toxicity, subchronic and chronic toxicity, reproductive toxicity, genotoxicity, photogenotoxicity, carcinogenicity, irritation, sensitization, phototoxicity and photosensitization as well as on environmental aspects. New challenges with respect to the safety of UV filters have arisen from the banning of animal experiments for the development of cosmetics. Future debates on sunscreens are likely to focus on nanoparticles and environmental issues, along with motivation campaigns to persuade consumers to protect their skin. However, more efficient sunscreen use will also continue to raise questions on the benefit in preventing vitamin D synthesis in the skin induced by sunlight.

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BACKGROUND: Port-wine stains (PWS) are congenital capillary malformations that persist throughout life. Laser therapy is a common treatment for PWS, and pulsed-dye laser is the current treatment of choice. AIM: To compare the clinical results on untreated PWS of two dye lasers with different wavelengths and pulse duration: a flashlamp-pumped dye laser (FPDL) and a long-pulse-duration dye laser (LPDL). METHODS: In total, 24 patients were treated on 4-6 test areas with both laser types using high-energy and low-energy fluences. An FPDL with 0.45 ms pulse duration tuned to 585 nm was compared with an LPDL with 1.5 or 3.0 ms pulse duration tuned to 595 nm. Twelve weeks later the degree of lightening was evaluated by a blinded assessor. Pain was assessed directly after treatment with both lasers, using a visual analogue scale. RESULT: There was no significant difference overall between the two systems in lightening of the lesion or in patient-reported pain. CONCLUSION: Both laser systems are equivalent in terms of efficacy and pain.

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BACKGROUND AND OBJECTIVES: Patients report well-being as they are treated with phototherapy. We investigated hormone parameters and psychological well-being after phototherapy in a placebo-controlled study. METHODS: A total of 77 patients with dermatological conditions and 22 healthy volunteers were divided into four groups. The patients received phototherapy either on the whole body or only on hands and/or feet. The volunteers were given either whole-body phototherapy or placebo light. Serum or plasma samples were analysed for cortisol, calcium, magnesium, phosphate, TSH, T(4), T(3) and 25-hydroxyvitamin D, and urine samples for cortisol. Patients and volunteers answered a questionnaire before and 6 weeks after phototherapy/placebo light. Psychiatric ratings were performed according to the Comprehensive Psychopathological Self-rating Scale for Affective Syndromes, a self-report version of which has been transformed to correspond to the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: In the patients who received whole-body irradiation, we observed a significant improvement in both MADRS score and cognitive-symptom score after the completion of phototherapy. We also observed a significantly higher level of 25-hydroxyvitamin D after phototherapy, but no difference in the other hormone parameters. CONCLUSION: Whole-body phototherapy of patients with dermatological conditions results in improved well-being and significantly higher levels of 25-hydroxyvitamin D in serum.

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BACKGROUND: There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL-PDT) may have potential. OBJECTIVES: To investigate the efficacy and tolerability of MAL-PDT for treatment of moderate inflammatory facial acne. PATIENTS/METHODS: Thirty patients aged 15-28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo-controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10-cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six-point rating scale. Data were analysed on an intention-to-treat basis, including all 30 patients. RESULTS: There was a statistically significant greater reduction in the total inflammatory lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction 54% [95% confidence interval (CI) 35-64%] vs. 20% (95% CI 8-50%), P = 0.0006. MAL-PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. CONCLUSIONS: MAL-PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.

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BACKGROUND: Port-wine stains (PWS) are congenital vascular malformations occurring in 0.3% of children. The pulsed dye laser is a well established treatment for PWS. OBJECTIVES: To compare, clinically and histologically, the effects of the flashlamp pulsed dye laser with the argon-pumped dye laser in the treatment of PWS. METHODS: Thirty patients were treated on two to four test areas with both laser types using different energy fluences. A flashlamp pulsed dye laser with 0.45 ms pulse duration and a spot size of 5 mm was compared with an argon-pumped dye laser, with a spot size of 1 mm delivered with a robotic scanning laser handpiece (Hexascan) and 70-190 ms pulse duration. Both were tuned to 585 nm. Twelve weeks later the degree of lightening was evaluated and biopsies were taken. To count the vessels the skin sections were stained with CD34 using an immunohistochemical technique. The vessels were divided into three groups by diameter (d): d < 10 microm, 10 < or = d < 20 microm, d > or = 20 microm. RESULTS: The clinical results showed a significantly better lightening using the flashlamp pulsed dye laser than with the argon-pumped dye laser. The histological results showed a significant decrease in the number of vessels of diameter larger than 20 microm in treated compared with untreated lesions. We found no histological difference in the number of vessels between the two laser treatments. However, there was a tendency towards more small vessels (diameter < 10 microm) after one treatment with the flashlamp pulsed dye laser compared with untreated PWS. CONCLUSIONS: The flashlamp pulsed dye laser is clinically superior to the argon-pumped dye laser in the treatment of PWS.

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There is no curative treatment for mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma. The aim of this study was to investigate the response of single lesions to photodynamic therapy (PDT). The study included 10 plaque MF lesions and 2 tumour MF lesions from 10 patients. First, 20% 5-aminolevulinic acid was applied topically to the lesion and adjacent skin for 5-6 h. The lesion was then exposed to red light at around 630nm. Skin biopsies were taken before treatment, after clinical improvement and after clinical remission. The expression of CD3, CD4, CD7, CD8, CD1a, CD34, CD68, CD71, Ki-67, bcl-2 and p53 was studied immunohistochemically. There was complete clinical clearance in seven of nine plaque lesions. Neither tumour lesion responded to PDT. The biopsies confirmed a regression of the infiltrate after treatment. In the sparse remaining infiltrate a few CD4+ and CD8+ cells were found, most of which showed normal bcl-2. There were also fewer proliferating cells, illustrated by a decrease in Ki-67 and CD71. In conclusion, PDT has good clinical and histological effects in treating local plaque MF lesions.

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BACKGROUND: Ultraviolet radiation (UVR) has a variety of effects on human skin. Best known are the effects of UVB (290-320 nm) and UVA2 (320-340 nm), which cause DNA damage and increased risk of cancer. However, the effects of UVA1 (340-400 nm) have been not completely investigated. METHODS: The effects of repetitive low doses of UVA1 and visible light were studied in 12 healthy individuals. A part of the buttock was exposed to 20 J/cm2 UVA1 and another part of 126 J/cm2 of visible light three times a week for 4 weeks. Repeated punch biopsies were taken during the 4 weeks of treatment and also 2 weeks after the last irradiation. The avidin-biotin-immunoperoxidase technique was used to investigate the expression of p53, p21WAF, bcl-2, Ki67 and cyclin A. RESULTS: By comparison to untreated skin, an increased expression of p53 but not p21WAF in keratinocytes was seen. The bcl-2 protein expression increased slightly after both UVA1 and visible light. An increased staining with Ki67 and cyclin A after UVA1 but not after visible light was observed as a sign of increased proliferation. CONCLUSION: These results suggest that suberythemal doses of UVA1 and even visible light may cause DNA damage.

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The standard wavelength in the treatment of port-wine stains (PWS) with the pulsed dye laser is 585 nm. In many cases, the response to therapy is not adequate despite many treatments, depending partly on vessels out of reach of the laser. Longer wavelengths penetrate deeper into the dermis, but are absorbed less by oxyhaemoglobin, and require higher fluences. In this study, 22 patients with PWS were treated with the flashlamp-pumped pulsed dye laser using two different wavelengths, 585 and 600 nm. Four adjacent sites with PWS were treated on one occasion with 585 nm, 600 nm and equal fluence, and with 1.5 and 2 times the 585 nm fluence. The test areas were examined blindly, by four evaluators, an average of 12.5 weeks later. There was significantly less lightening with 600 nm than with 585 nm (P < or = 0.001) when equal fluences were used. When 1.5 and 2 times the 585 nm fluence were applied, with 600 nm the lightening was equal to that after 585 nm. However, in individual cases (11 of 22) 600 nm showed a superior lightening of at least 20% compared to 585 nm. There was slight hyperpigmentation and hypopigmentation, but no atrophy or scarring. In conclusion, 585 nm remains the wavelength of choice in treatment of PWS with the pulsed dye laser. However, in cases that do not respond satisfactorily with 585 nm, it may be worth trying 600 nm with a fluence that is at least 1.5-2 times the 585 nm fluence.

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Solar urticaria is characterized by itching weals that occur a few minutes after exposure to visible or ultraviolet light. The symptoms may sometimes restrict normal daily life. Treatment is difficult in more severe cases. We describe one patient with solar urticaria who was successfully treated with cyclosporin A. The patient had first been treated with antihistamine, PUVA and chloroquine phosphate without effect. Cyclosporin was given in a dose of 4.5 mg/kg body weight/day. Phototesting before, during and after treatment showed a decreased light sensitivity to UVA, UVB and visible light during cyclosporin treatment compared with phototesting before therapy. The patient could be out in the sun for at least 1 h with minimal urticaria during cyclosporin therapy compared with only a few minutes previously. However, 1-2 weeks after cyclosporin therapy was discontinued, skin symptoms returned. Cyclosporin therapy is a possible treatment in severe cases of solar urticaria where other treatments have failed, especially in countries where treatment is necessary only for a few months during summer.

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Sections of human skin were processed according to the indirect immunofluorescence technique with a rabbit antiserum against human protein gene product 9.5 (PGP 9.5). Immunoreactivity was detected in intraepidermal and dermal nerve fibres and cells. The intraepidermal nerves were varicose or smooth with different diameters, running as single processes or branched, straight or bent, projecting in various directions and terminating in the stratum basale, spinosum or granulosum. The density of the intraepidermal nerves varied between the different skin areas investigated. PGP 9.5-containing axons of the lower dermis were found in large bundles. They separated into smaller axon bundles within the upper dermis, entering this portion of the skin perpendicular to the surface. Then they branched into fibres mainly arranged parallel to the epidermal-dermal junctional zone. However, the fibres en route to the epidermis traversed the upper dermis more or less perpendicularly. Furthermore, immunoreactive dermal nerve fibres were found in the Meissner corpuscles, the arrector pili muscles, hair follicles, around the eccrine and apocrine sweat glands and around certain blood vessels. Such fibres were also observed around most subcutaneous blood vessels, sometimes heavily innervating these structures. Numerous weakly-to-strongly PGP 9.5-immunoreactive cells were found both in the epidermis and in the dermis.

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