The utility of hand-held mobile spirometer technology in a resource-constrained setting.

BACKGROUND: Mobile phone-linked spirometry technology has been designed specifically for evaluating lung function at primary care level. The Air-Smart Spirometer is the first mobile spirometer accepted in Europe for the screening of patients with chronic respiratory diseases. OBJECTIVES: To prospectively assess the accuracy of the device in measuring forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in a South African population, and to investigate the ability of the device to detect obstructive ventilatory impairment. METHODS: A total of 200 participants were randomly assigned to perform spirometry with either the mobile spirometer connected to a smartphone or the desktop spirometer first, followed by the other. The FEV1/FVC ratio as well as the absolute FEV1 and FVC measurements were compared, using each participant as their own control. A Pearson correlation and Bland-Altman analysis were performed to measure the agreement between the two devices. We defined obstructive ventilatory impairment as FEV1/FVC <0.7 measured by desktop spirometry in order to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Air-Smart Spirometer. RESULTS: There was a strong correlation between the absolute FEV1 and FVC values and FEV1/FVC ratio measured with the mobile Air-Smart Spirometer and more conventional pulmonary function testing, with r=0.951, r=0.955 and r=0.898, respectively. The Air-Smart Spirometer had a sensitivity of 97.6%, specificity of 74.4%, PPV of 73.0% and NPV of 97.8% for obstructive ventilatory impairment. CONCLUSIONS: The mobile Air-Smart Spirometer compared well with conventional spirometry, making it an attractive and potentially affordable tool for screening purposes in a primary care setting. Moreover, it had a high sensitivity and NPV for obstructive ventilatory impairment.

Children sustain high levels of skin DNA photodamage, with a modest increase of serum 25-hydroxyvitamin D3 , after a summer holiday in Northern Europe.

BACKGROUND: Childhood solar ultraviolet radiation (UVR) exposure increases the risk of skin cancer in adulthood, which is associated with mutations caused by UVR-induced cyclobutane pyrimidine dimers (CPD). Solar UVR is also the main source of vitamin D, essential for healthy bone development in children. OBJECTIVES: To assess the impact of a 12-day Baltic Sea (54° N) beach holiday on serum 25-hydroxyvitamin D3 [25(OH)D3 ] and CPD in 32 healthy Polish children (skin types I-IV). METHODS: Blood and urine were collected before and after the holiday and assessed for 25(OH)D3 and excreted CPD, respectively, and personal UVR exposure was measured. Diaries were used to record sunbathing, sunburn and sunscreen use. Before- and after-holiday skin redness and pigmentation were measured by reflectance spectroscopy. RESULTS: The average ± SD daily exposure UVR dose was 2·4 ± 1·5 standard erythema doses (SEDs), which is borderline erythemal. The mean concentration of 25(OH)D3 increased (× 1·24 ± 0·19) from 64·7 ± 13·3 to 79·3 ± 18·7 nmol L-1 (P < 0·001). Mean CPD increased 12·6 ± 10·0-fold from 26·9 ± 17·9 to 248·9 ± 113·4 fmol µmol-1 creatinine (P < 0·001). Increased 25(OH)D3 was accompanied by a very much greater increase in DNA damage associated with carcinogenic potential. Overall, skin type had no significant effects on behavioural, clinical or analytical outcomes, but skin types I/II had more CPD (unadjusted P = 0·0496) than skin types III/IV at the end of the holiday. CONCLUSIONS: Careful consideration must be given to the health outcomes of childhood solar exposure, and a much better understanding of the risk-benefit relationships of such exposure is required. Rigorous photoprotection is necessary for children, even in Northern Europe.

Defining "intermittent UVR exposure".

BACKGROUND: Cutaneous malignant melanoma (CMM) has been associated with "intermittent UVR exposure", which in previous studies has mainly been assessed by retrospective questionnaire data. Further, there is no uniform definition of the term "intermittent UVR exposure". OBJECTIVES: We aimed to define and quantify "intermittent UVR exposure" by an objective measure. METHODS: A broad study population of adults and children had data collected during a summer period. Data were personal UVR dosimetry measurements, from which the number of "intermittent days" was derived, sun behaviour diaries and retrospective questionnaires. Two definitions of intermittent UVR exposure were tested: (1) days when UVR dose exceeded 3 times individual average daily UVR dose, and (2) days when UVR dose exceeded individual constitutive skin type. Measures of nevi and lentigines were used as surrogates for CMM. RESULTS: Using the first definition based solely on UVR dosimetry data we found 1241 "intermittent days" out of a total of 17 277 days (7.2%) among 148 participants. The numbers for nevi and lentigo density were significantly predicted by the number of intermittent days (R(2) = 0.15 and R(2) = 0.40, p < 0.001). The corresponding numbers for prediction of nevi and lentigo density by retrospective questionnaire data was lower (R(2) = 0.11, R(2) = 0.26, p < 0.001). CONCLUSIONS: We introduce a well-defined objective measure of intermittent UVR exposure. This measure may provide a better prediction of solar skin damage and CMM than retrospective questionnaire data.

Personal UVR exposure of farming families in four European countries.

BACKGROUND: The main risk factor for skin cancer is ultraviolet radiation (UVR). Farming families living in rural areas with easy outdoor access may experience excessive UVR exposure. Differences between countries in latitude, altitude and sun behaviour could result in different personal UVR exposures. However, no studies have examined this until now. OBJECTIVES: To determine personal UVR exposure in work and leisure situations among farming families in Europe. METHODS: Prospective cohort study of farmers, their partners (spouses) and children in Denmark (DK), Poland (PL), Austria (AT), and Spain (ES) from 2009 to 2011. Personal UVR exposure and sun behaviour were recorded by dosimetry and diaries. RESULTS: Farmers' average daily UVR exposure on working days ranged from 1.4 SED (DK, AT) to 2.7 SED (ES). Corresponding figures for partners were: 0.6 SED (DK) to 1.9 SED (PL), and for children (day-care/school days): 0.7 SED (ES) to 1.3 SED (PL). DISCUSSION AND CONCLUSIONS: Farmers' UVR exposure was comparable to that of outdoor workers in previous studies and exceeded the recommended UVR exposure limits on 36% (DK, AT), 29% (PL) and 56% (ES) of their working days. Attention to sun protection for outdoor workers across Europe in preventing UVR-induced skin cancer is still needed.

UVR exposure and vitamin D in a rural population. A study of outdoor working farmers, their spouses and children.

BACKGROUND: Living and working in the countryside may result in excessive UVR exposure, with increased risk of skin cancer. Some sun exposure is, however, recommended, since vitamin D production is UVB-dependent. OBJECTIVES: To examine UVR exposure and vitamin D levels in a rural population of outdoor working male farmers, their indoor working spouses and their children, expected to receive high UVR exposure. METHODS: Prospective, cohort study. During the summer 2009 daily, personal UVR exposure and sun behaviour were recorded by dosimetry and diaries (17 403 days). Vitamin D was measured at the end of summer and the following winter. RESULTS: Risk behaviour (= exposure of shoulders/upper body to the sun), beach days, sunscreen use and sunburns were infrequent. Farmers and boys had the highest daily UVR exposure (both 1.5 SED per day), likewise on work days. On non-work days the UVR exposure was even higher (up to 2.0 SED per day). Farmers, girls and boys had a higher chronic UVR exposure than the spouses, who had more intermittent high UVR exposure. Vitamin D levels did not differ between family members. At the end of summer 16% of the participants were vitamin D insufficient, the following winter, 61%. Some UVR exposure variables correlated positively, but weakly, with vitamin D levels. CONCLUSIONS: UVR exposure was generally high among this study population, however, vitamin D levels still dropped below the recommended level during winter for most participants. Differences in UVR exposure between the groups did not result in differences in vitamin D levels.

Determinants of personal ultraviolet-radiation exposure doses on a sun holiday.

BACKGROUND: A great number of journeys to sunny destinations are sold to the Danish population every year. We suspect that this travel considerably increases personal annual ultraviolet-radiation (UVR) exposure doses. This is important because such exposure is the main cause of skin cancer, and studies have shown a correlation between intermittent solar UVR exposure and malignant melanoma. OBJECTIVES: To prospectively monitor the behaviour of a group of sun seekers during a winter sun holiday and to study the impact of behaviour on personal UVR exposure doses. METHODS: In this observational study 25 Danish sun seekers were closely monitored by on-site investigators for 6 days during a winter sun holiday in the Canary Islands, thus avoiding the possible recall bias of retrospective studies with questionnaires. The volunteers recorded their location, clothing and sunscreen use in diaries, and their UVR doses were measured by personal UVR dosimeters worn on the wrist. This resulted in 3450 half-hour registrations during 150 participation days. RESULTS: On average, each volunteer received a total UVR dose of 57 standard erythema doses over 6 days, which is 43% of the annual UVR dose of a Danish indoor worker. Their exposed body area, sunscreen use and percentage of body with sunscreen application were positively correlated with their personal UVR doses, and there was also a strong relationship between location and UVR doses received. CONCLUSIONS: The behaviour of the volunteers had a major impact on their personal UVR doses. Our results emphasize the importance of changing the behaviour of sun seekers with protanning attitudes to reduce their personal annual UVR exposure doses, and possibly their risk of skin cancer.

Weather conditions and daylight-mediated photodynamic therapy: protoporphyrin IX-weighted daylight doses measured in six geographical locations.

BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated methyl aminolaevulinate PDT (daylight-PDT) is a simple and painless treatment procedure for PDT. All daylight-PDT studies have been performed in the Nordic countries. To be able to apply these results in other parts of the world we have to compare the daily protoporphyrin IX (PpIX) light dose in other countries with the PpIX light doses found in Nordic countries. OBJECTIVES: To calculate where and when daylight-PDT of AKs was possible in six different geographical locations using ground stations measuring PpIX-weighted daylight doses. METHODS: PpIX-weighted daylight doses were measured using a dosimeter with a customer-specific photodiode with a detector sensitivity that mimics the PpIX absorption spectrum and measures in 'PpIX doses'. The dosimeters were built into ground stations that were placed in six geographical locations measuring from July to December 2008. Temperature data for each location were obtained from the internet. The maximal ultraviolet (UV) index for Copenhagen was obtained for the measuring period of the dosimeters. RESULTS: If the PpIX light dose should be above 8Jcm(-2) and the maximum temperature of the day at least 10°C, it was possible to treat patients on nearly all days until the middle of September in Reykjavik and Oslo, until the last week of October in Copenhagen and Regensburg, until the middle of November in Turin and all year in Israel. CONCLUSIONS: Where and when to perform daylight-PDT depends on the PpIX light dose and outdoor temperature. The PpIX light dose was influenced by the geographical location (latitude), weather condition and time of year. The UV index was not more suitable than temperature and weather to predict if the intensity of daylight would be sufficient for daylight-PDT.

Sun behaviour after cutaneous malignant melanoma: a study based on ultraviolet radiation measurements and sun diary data.

BACKGROUND: It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. OBJECTIVES: In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun behaviour. METHODS: The study population consisted of 24 patients recently diagnosed with CMM during the 7 months preceding the start of the study; 51 controls who matched these recently diagnosed patients in age, sex, occupation and constitutive skin type; and 29 patients diagnosed with CMM between 12 months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. RESULTS: The UVR dose of recently diagnosed patients on days with body exposure was one-third lower, and the number of days using sunscreen was double that of matched controls. However, in patients diagnosed more than 12 months earlier, the UVR dose on days with body exposure was one-third higher and the number of days using sunscreen was half that of recently diagnosed patients. CONCLUSIONS: Patients with CMM limited their UVR dose on days with body exposure, and by using sunscreen further reduced UVR reaching the skin, although only immediately after diagnosis.

Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study.

BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. OBJECTIVES: In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. METHODS: One hundred and forty-five patients with a total of 2768 AKs (severity grades I-III) of the face and scalp were randomized to either 1½ or 2½ h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. RESULTS: No difference in lesion response was found between the 1½ and 2½ h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P < 0·0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3·5 J cm(-2). CONCLUSIONS: Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.

A randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp.

BACKGROUND: Actinic keratoses (AKs) are common dysplastic skin lesions that may differentiate into invasive squamous cell carcinomas. Although a superior cosmetic outcome of photodynamic therapy (PDT) is advantageous compared with equally effective treatments such as cryotherapy and curettage, the inconvenience of clinic attendance and discomfort during therapy are significant drawbacks. Daylight-mediated PDT could potentially reduce these and may serve as an alternative to conventional PDT. OBJECTIVES: To compare the efficacy of methyl aminolaevulinate (MAL)-PDT with 1½ vs. 2½ h of daylight exposure in a randomized multicentre study. METHODS: One hundred and twenty patients with a total of 1572 thin AKs of the face and scalp were randomized to either 1½- or 2½-h exposure groups. After gentle lesion preparation and application of a sunscreen of sun protection factor 20, MAL was applied to the entire treatment area. Immediately after, patients left the clinic and exposed themselves to daylight according to the randomization. Daylight exposure was monitored with a wristwatch dosimeter and patients scored their pain sensation during treatment. RESULTS: The mean lesion response rate at 3 months was 77% in the 1½-h group and 75% in the 2½-h group (P = 0·57). The mean duration of daylight exposure was 131 and 187 min in the two groups. The mean overall effective light dose was 9·4 J cm(-2) (range 0·2-28·3). Response rate was not associated with effective daylight dose, exposure duration, treatment centre, time of day or time of year during which the treatment was performed. Treatment was well tolerated, with a mean ± SD maximal pain score of 1·3 ± 1·5. CONCLUSIONS: Daylight-mediated MAL-PDT is an effective, convenient and nearly pain-free treatment for patients with multiple thin AKs. Daylight-mediated PDT procedures were easily performed and 2 h of daylight exposure resulted in uniformly high response rates when conducted in the period from June to October in Nordic countries.

Skin autofluorescence as a biological UVR dosimeter.

BACKGROUND/PURPOSE: Collagen is one of the major endogenous skin fluorophores. Alteration in the structure of collagen due to chronic ultraviolet radiation (UVR) exposure may influence the intensity of the autofluorescence. The aim of this study was to investigate the relation between collagen-linked autofluorescence and sun exposure to clarify whether the skin can be used as a biological UVR dosimeter. METHODS: We conducted an in vivo study with 131 healthy volunteers. Fluorescence was measured from sun-exposed (dorsal forearm, forehead and shoulder) and sun-protected (buttock) skin and corrected for the impact of pigmentation and redness. The excitation wavelengths (Ex) and emission wavelengths (Em) were: Ex330:Em370, Ex330:Em455 and Ex370:Em455 nm. Individual UVR exposure data were collected both retrospectively and prospectively using questionnaires and electronic personal UVR dosimeters for a summer period. RESULTS: Age, but not sex, skin type or smoking habits correlated significantly positively with skin autofluorescence at Ex370:Em455 at all body sites (P<0.001, r(2)=0.08-0.26), and at Ex330:Em455 only at the buttock (P=0.001, r(2)=0.08), whereas age was not correlated with Ex330:Em370. Sun-protected buttock skin had significantly higher autofluorescence than sun-exposed skin (P-values<0.0001). Because of great between-subject differences in autofluorescence at different body sites, and because the autofluorescence at the unexposed buttock represents the baseline value, individual correction of skin autofluorescence measurement with that of the buttock was performed. Different measures of individual chronic cumulative UVR doses correlated significantly negatively with the skin autofluorescence ratio (F(ratio)), but the correlations were poor (r(2)=0.03-0.10). CONCLUSION: The results indicate that the collagen-linked skin F(ratio) might be best to use as a measure of individual photodamage, a UVR dose effect, and that it is also a better marker of individual cumulative UVR dose than the used UVR exposure measurements. The methods used to obtain UVR exposure data might not be sensitive and specific enough.

A crystalline test specimen for checking the performance of high-resolution electron microscopes.

A thin single crystal (001) film of gold with a favourable perforation is described. Examples of its versatile applications to test procedures and calibrations in high-resolution electron microscopy are illustrated. The advantage of such gold films mainly results from the good visibility of dark-field/bright-field image displacements at perforation edges in well defined crystallographic orientations.

[Possibilities and limits of electron microscopy (author's transl)]. / Möglichkeiten und Grenzen der Elektronenmikroskopie.

This review evaluates the electron microscopical imaging techniques used today. Reviewed are transmission method, indirect imaging of surfaces by replica and surface decoration, and direct imaging of surfaces by means of scanning, emission, and mirror electron microscopy. For each method the respective limit of resolution and the possibilities of application are described. Especially, the methods of high-resolution and of high-voltage electron microscopical techniques will be pointed out as being actual means of investigation stressing electron microscopy up to the limits given by physics and technique.