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Primary and additional treatment preference in aggressive retinopathy of prematurity and type 1 retinopathy of prematurity
http://orcid.org/0000-0002-9501-9892Ji Hye Jang1,
Yong Koo Kang2,
Han Sang Park2,
Kiyoung Kim3,
Sung Soo Kim4,
Jae Yong Han4,
Hyun Wong Kim5,
Jong Wook Bang5,
Jae Shin Song6,
http://orcid.org/0000-0003-0542-2758Sang Jun Park6,
http://orcid.org/0000-0003-3692-7169Se Joon Woo6,
Kwang Sic Joo6,
Woong-Sun Yoo7,
Inyoung Chung7,
Yong-Wun Cho7,
Jong Hyun Lee8,
Hun Jin Choi8,
http://orcid.org/0000-0002-6871-6721Yoo-Ri Chung9
1Department of Ophthalmology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
2Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu, Korea (the Republic of)
3Department of Ophthalmology, Kyung Hee University School of Medicine, Seoul, Korea (the Republic of)
4The Institute of Vision Research, Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seodaemun-gu, Korea (the Republic of)
5Department of Ophthalmology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea (the Republic of)
6Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
7Department of Ophthalmology, Gyeongsang National University School of Medicine, Jinju, Korea (the Republic of)
8Department of Ophthalmology, Ilsan Paik Hospital, Inje University College of Medicine, Busan, Korea (the Republic of)
9Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea (the Republic of)
Correspondence to Dr Ji Hye Jang; mjmom99{at}naver.com
Objective This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP.
Methods This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed.
Results Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment.
Conclusion In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.
Treatment Lasers
Data are available on reasonable request.
Current treatments for aggressive retinopathy of prematurity (ROP) and type 1 ROP include intravitreal antivascular endothelial growth factor (anti-VEGF) injection or laser ablation.
Anti-VEGF agents were chosen as the primary treatment when the ROP zone was located in the central region, and laser ablation was selected when the zone was located in the peripheral retina. Anti-VEGF injections were preferred for aggressive ROP over type 1 ROP, and higher doses were used in aggressive ROP. If additional treatment was required, laser ablation was selected as a secondary treatment.
These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.
Retinopathy of prematurity (ROP) is a disease that occurs in preterm infants due to the abnormal development of retinal blood vessels, in which neovascular proliferation occurs at the junction of the vascular-avascular retina or within the vascularised retina, progressing to tractional retinal detachment.1 2 This is one of the leading causes of low vision and vision loss in children and can be prevented if treated promptly.3
Innovations in retinal imaging have changed the concepts of ROP zone, stage and plus disease.4–6 The International Classification of ROP, Third Edition (ICROP3),7 defines the term the posterior zone II as an area of two disc diameters between zone I and zone II, describes a continuous spectrum of vascular changes from normal to plus disease and recommends the use of the term aggressive ROP instead of aggressive posterior ROP. Therefore, it is necessary to study whether the new classification of ROP cases based on the ICROP3 differs from the existing ROP classification in terms of disease progression and treatment effects.
Recently, antivascular endothelial growth factor (anti-VEGF) agents have emerged as a promising alternative to laser therapy for the treatment of ROP. The Bevacizumab Eliminate the Angiogenic Treat (BEAT)-ROP study8 reported that intravitreal bevacizumab (Avastin, Genentech Inc, San Francisco, California, USA) injection was more effective than laser ablation for zone I stage 3+ROP. In addition, the RAINBOW trial9 showed that infants treated with ranibizumab 0.2 mg (Lucentis, Genentech Inc) had superior efficacy compared with laser therapy. Therefore, the use of anti-VEGF agents for ROP treatment is expected to increase rapidly. However, studies on the extent and dose of bevacizumab or ranibizumab in real clinical practice are lacking.
Incomplete regression and reactivation of ROP after anti-VEGF treatment have become important issues to note after the acute phase of ROP.10 11 It is not clear which treatment is actually selected by a retinal specialist when ROP is reactivated. Therefore, treatment guidelines for ROP reactivation after intravitreal anti-VEGF injections are required.
Therefore, we aimed to investigate the treatment options and short-term outcomes in aggressive ROP and type 1 ROP, including the actual doses of anti-VEGF agents and the additional treatment tendencies with recurrence or incomplete regression.
This was a retrospective multicentre study in which members of the Korean Retina Society participated. Details about the purpose of the study, inclusion and exclusion criteria were communicated to members who expressed an interest in participating in the study, and data were collected via a case report form (CRF) for analysis.
From 1 January 2020 to 31 December 2021, preterm infants with gestational age (GA) less than 37 weeks were examined. Infants who died before the follow-up examination and those who were transferred to another hospital were excluded. Diagnosis and classification of ROP were performed by expert retinal specialists at each hospital according to the ICROP3.7
Preterm infants with ROP who required treatment were enrolled in this study (online supplemental figure 1). All eyes with treatment-requiring ROP were classified as type 1 ROP or aggressive ROP. If both eyes received different treatments, then each eye of the infant was included separately in each treatment group. Demographic data, such as sex, GA at birth and birth weight (BW), were collected from the medical records. Ophthalmological data including postmenstrual age (PMA) at every examination, ROP subtype at diagnosis, primary treatment choice, duration of plus disease disappearance after primary treatment, retinal state at every examination, need for additional treatment, secondary treatment choice and local or systemic complications were collected via CRF. Furthermore, the locations of treatment-requiring ROP at diagnosis were divided into zones I, posterior zone II and zone II. For treatment, it was investigated which of the following three treatments would be used as the primary treatment: intravitreal anti-VEGF injection therapy, laser ablation therapy or combination (anti-VEGF injection is administered with laser ablation in the same day) therapy. If intravitreal injection therapy was chosen, the anti-VEGF agents and injection dosages were recorded.
Cases with insufficient treatment or recurrent ROP were further analysed. Insufficient treatment was defined as a case in which the lesion did not completely disappear and the plus disease persisted even after the first treatment within 4 weeks. Reactivation was defined as the reappearance of plus disease or the recurrence of lesions above the ridge stage at the advancing edge after 4 weeks. When additional treatment was administered, the trends in selecting secondary treatment options for additional treatment, the selected anti-VEGF injection agent and dose were investigated. Treatment failure was considered if it progressed to tractional retinal detachment and required surgery, if the ROP was so severe that ophthalmological examination was not possible or if further treatment was discontinued. Furthermore, during the follow-up period, monitoring was conducted to determine if there were any adverse reactions or events following additional treatment.
The demographic data of this study were collected and analysed by the participants. Ophthalmological data were collected and analysed by eye, not by subject. Continuous variable data, such as GA, BW, PMA and duration, were expressed as mean±SD. Discrete variables were expressed as numbers and percentages. IBM SPSS Statistics (V.25.0; IBM Corp, Armonk, New York, USA) was used to statistically analyse the collected data, and statistical significance was set at p<0.05.
Characteristics depending on the treatment-requiring ROP subtype
A total of 176 eyes of 94 infants (12 eyes in unilateral cases) received primary treatment; only these eyes were included in this study. In six eyes (three infants), both eyes received the same treatment on different days. In six eyes (three infants), each eye received different treatments and were included in each treatment subgroup. Table 1 shows the demographic and clinical characteristics of the infants with type 1 ROP or aggressive ROP.
The demographic and clinical characteristics of the infants with type 1 ROP or aggressive ROP
The mean GA for type 1 ROP was 25.7±1.8 weeks, while the mean GA for aggressive ROP was 25.2±2.0 weeks. The mean BW for type 1 ROP was 832.01±274.84 g, whereas it was 824.21±311.87 g for aggressive ROP, indicating no statistical significance between the two groups. The location of type 1 ROP at primary treatment was 18:34:79 for zone I: posterior zone II: zone II, whereas the location of aggressive ROP was 20:6:19, indicating that lesions occurred more frequently in the zone I area in aggressive ROP than in type 1 ROP (44.25% vs 13.74%, p<0.0001). The mean values of PMA at primary treatment were 38.3±6.1 weeks in type I ROP and 35.6±3.4 weeks in aggressive ROP, indicating significantly different between groups. In the type I ROP group, intravitreal anti-VEGF injection was administered as the primary treatment in 97 eyes (74.05%), laser ablation in 32 eyes (24.42%) and combination therapy in two eyes (1.53%). In the aggressive ROP group, anti-VEGF drugs in 40 eyes (88.89%) and laser ablations in five eyes (11.11%) were selected as the primary treatment. After primary treatment, the mean duration of plus disease disappearance was 17.9±16.3 days for type 1 ROP (two eyes, did not disappear plus disease until retreatment was decided) and 28.7±14.1 days for aggressive ROP (four eyes, did not disappear), indicating significant differences between groups. Thirty-five eyes (26.72%) with type 1 ROP and 25 eyes (55.56%) with aggressive ROP required additional treatment after initial treatment, which was 2.08 times higher than that of type 1 ROP.
Primary treatment choice and response to treatment in type 1 ROP
Type 1 ROP was diagnosed in 131 eyes of 70 preterm infants. Anti-VEGF injections were administered to 97 eyes (intravitreal bevacizumab injections in 37 eyes and intravitreal ranibizumab injections in 60 eyes), laser therapy in 32 eyes and combination therapy in two eyes as the primary treatment (table 2).
Primary treatment choice and response to treatment in type 1 retinopathy of prematurity (ROP)
In the type 1 ROP bevacizumab-treated subgroup (n=39 eyes), the ROP zone at primary treatment was zone I in six eyes, posterior zone II in 10 eyes and zone II in 21 eyes. The injection dosage of bevacizumab was 0.625 mg/0.025 mL in 12 eyes (half of the adult dose for treatments of macular oedema and age-related macular degeneration), 0.5 mg in 12 eyes, 0.375 mg in 6 eyes and 0.2 mg in 10 eyes. It took 11.6±8.4 days after injections for plus disease to completely disappear. During follow-up examination, reactivation of ROP was observed in 10 eyes, and the mean periods from primary treatment to secondary treatment was 38.6±9.8 days. In all cases of reactivated ROP, laser therapy was performed as a secondary treatment, and there was no progression to retinal detachment.
In the type 1 ROP ranibizumab-treated subgroup (n=60 eyes), the zone of type 1 ROP was located in zone I in 10 eyes, posterior zone II in 21 eyes and zone II in 29 eyes. The injection dosage was 0.2 mg/0.02 mL (the same dose as performed in the RAINBOW study) in 48 eyes and 0.1 mg in 12 eyes. It took 14.7±14.5 days for plus disease to completely disappear after injection, but plus disease did not disappear in two eyes, until retreatment was performed. Additional treatment-requiring ROP occurred in 25 eyes, and their mean time to retreatment was 71.8±38.0 days.
Laser therapy was performed as the primary treatment for 32 eyes. At the time of treatment, the zone of type 1 ROP was located in zone I in 2 eyes, posterior zone II in 3 eyes and zone II in 27 eyes. After laser treatment, it took 34.1±26.2 days for the plus disease to completely disappear, and there were no cases that required additional treatment.
Combination therapy was performed in two eyes of two infants. In two cases, coadministration of anti-VEGF agent was 0.5 mg and 0.25 mg of bevacizumab, respectively, and no secondary treatment was required during the follow-up period.
Primary treatment choice and response to treatment in aggressive ROP
Among the 45 eyes of 24 preterm infants with aggressive ROP, 40 eyes (7 eyes of bevacizumab, 33 eyes of ranibizumab) selected anti-VEGF injection and five eyes selected laser treatment as their primary treatment (table 3).
Primary treatment choice and response to treatment in aggressive retinopathy of prematurity (ROP)
In the aggressive ROP bevacizumab-treated subgroup (n=7), the ROP zone at the first treatment was zone 1 in one eye, zone 2 in two eyes and zone 2 in four eyes. The injection dosage of bevacizumab was 0.625 mg in five eyes and 0.5 mg in two eyes. It took an average time of 47.6±12.7 days for plus disease to disappear after bevacizumab treatment. Both eyes receiving 0.5 mg of bevacizumab had insufficient regression within 4 weeks and required further treatment.
In the aggressive ROP ranibizumab-treated subgroup (n=33), ROP lesion were located in zone I in 19 eyes, posterior zone II in 4 eyes and zone II in 10 eyes; the injection dosage for treatment was 0.25 mg for 9 eyes, 0.2 mg for 16 eyes and 0.1 mg for 8 eyes. In 29 eyes, plus disease disappeared after the first injections, which took 22.1±25.8 days on average. However, it did not completely disappear in four eyes; therefore, additional treatment was required. Additional treatment was performed for 21 eyes, including three eyes because of a lack of treatment and 18 eyes because of reactivation. The mean interval time between primary treatment and additional treatment was 62.3±40.9 days. During the follow-up period, none of the patients progressed to retinal detachment.
Laser therapy was primarily performed in five eyes, and the lesions were located in zone II in all eyes. In three eyes, plus disease disappeared after primary treatment, which took 20.2±11.3 days. However, because plus disease in two eyes did not disappear within 4 weeks, it was regarded as a lack of treatment, and secondary treatment was performed. During the follow-up period, none of the patients progressed to retinal detachment.
Additional treatment due to reactivation and lack of treatment
In 34.09% of all cases, additional treatment was required because of insufficient treatment and ROP reactivation after the primary treatment. In type 1 ROP, additional treatment was performed in 35 eyes (26.72%) out of 131 eyes (figure 1). In the bevacizumab-treatment subgroup of type 1 ROP, 10 out of 37 eyes received secondary treatment. Reactivation occurred in two eyes injected with 0.625 mg bevacizumab, four eyes injected with 0.5 mg bevacizumab and four eyes injected with 0.325 mg bevacizumab during primary treatment. Reactivation occurred in two eyes (2/6, 33.3%) with an initial ROP located in zone I, four eyes (4/10, 40.0%) in posterior zone II and two eyes (2/21, 9.5%) in zone II. Laser therapy was additionally performed as a secondary treatment for all eyes, and no further treatment was required. In the type 1 ROP ranibizumab-treatment subgroup, 25 out of 60 eyes received additional treatment, and all of them received ranibizumab 0.2 mg injection as the primary treatment. Regarding the ROP zone at primary treatment, additional treatment was done 7 eyes (7/10, 70.0%) in zone I, 8 eyes (8/21, 38.1%) in posterior zone II, 10 eyes (10/29, 34.5%) in zone II. Two eyes were treated with laser ablation due to a lack of treatment. In addition, 23 eyes were treated as a result of ROP reactivation, among which 19 received laser therapy and 5 received ranibizumab 0.2 mg injections. In one eye, where ranibizumab was injected twice consecutively, the therapeutic effect was insufficient; therefore, laser treatment was additionally performed 93 days after the second treatment. Reactivation did not occur in the laser therapy or combination therapy groups; therefore, secondary treatment was not required.
Additional treatment choice trends in cases of reactivation or lack of primary treatment in type 1 retinopathy of prematurity (ROP). The flow chart shows the number of eyes that received at least one additional treatment. Additional treatment was performed within 4 weeks of the primary treatment because of a lack of treatment. If ROP was reactivated, it was performed 4 weeks after the primary treatment. The initial ROP zone was divided into zone I: posterior zone II: zone II, and the corresponding cases (eyes) was indicated with a number. B, bevacizumab; R, ranibizumab.
Secondary treatment was performed in 25 (55.56%) out of 45 eyes with aggressive ROP, and none of the eyes progressed to retinal detachment during the follow-up period (figure 2). In the aggressive ROP bevacizumab-treatment subgroup, only two eyes injected with bevacizumab 0.5 mg as the primary treatment received additional treatment due to lack of treatment. One eye that received laser treatment as secondary treatment no longer required additional treatment. In the other eye, where the plus disease did not disappear even 1 week after the first injection, 0.625 mg of bevacizumab was injected as an additional treatment. However, there was no improvement after the second injection, and the laser treatment was administered 23 days later.
Additional treatment choice trends in cases of reactivation or lack of primary treatment in aggressive retinopathy of prematurity (ROP). The flow chart shows the number of eyes that received at least one additional treatment. Additional treatment was performed within 4 weeks of the primary treatment because of a lack of treatment. If ROP was reactivated, it was performed 4 weeks after the primary treatment. The initial ROP zone was divided into zone I: posterior zone II: zone II, and the corresponding cases (eyes) was indicated with a number. B, bevacizumab; R, ranibizumab.
In the aggressive ROP ranibizumab-treatment subgroup, additional treatment was performed for 21 eyes, which included 6 out of 9 eyes with 0.25 mg of ranibizumab injected, 10 out of 16 eyes with 0.2 mg injected and 5 out of 8 eyes with 0.1 mg injected during primary treatment. Additional treatment was performed in 13 eyes (13/19, 68.4%) in zone I, two eyes (2/4, 50.0%) in posterior zone II, six eyes (6/9, 66.7%) in zone II. Owing to insufficient treatment, three eyes received secondary treatment, among which two eyes received laser therapy and one eye received anti-VEGF injection treatment consecutively. Secondary treatment was performed in 18 eyes with recurrent ROP. Laser treatment was performed in 10 eyes, ranibizumab injection in six eyes and combination therapy in two eyes. In all cases in which the second injection of ranibizumab was administered, the same or higher dose than the first injection was selected. Among the two consecutive injections of ranibizumab, one eye did not regress; therefore, laser ablation was performed as the third treatment. In the laser therapy group, secondary treatment was performed in two out of five eyes due to insufficient treatment. At that time, one eye received additional laser treatment and the other eye was treated in combination with bevacizumab 0.625 mg.
Based on multicentre clinical data, this study was divided into type 1 ROP and aggressive ROP, investigated the tendency to select anti-VEGF injections and laser ablation as the primary treatment in real clinical settings, the injection dose and frequency and the need for additional treatment after primary treatment.
The study findings are summarised as follows: (1) when selecting primary treatment, retinal specialists selected anti-VEGF injections when the ROP zone was located closer to the central area, whereas they selected laser therapy when lesions were located in the peripheral area, indicating a preference for anti-VEGF injections for aggressive ROP rather than type 1 ROP; (2) the dose of anti-VEGF injections administered by retinal specialists varied, and a higher dose was injected into the vitreous cavity in aggressive ROP than in type 1 ROP; (3) 34.09% of the eyes receiving primary treatment received additional treatment due to the lack of treatment and reactivation of ROP, which occurred more frequently with anti-VEGF injection than with laser treatment, and more frequently required additional treatment, especially in aggressive ROP; (4) if additional treatment was required, laser therapy was preferentially selected. However, if an anti-VEGF injection was selected, it was administered at a dose equal to or greater than the primary injection dose.
The key to treating type 1 ROP and aggressive ROP is to reduce the amount of VEGF in the retina and vitreous cavity.1 Current treatment are laser ablation, which burns the avascular retina to reduce the number of retinal cells that produce VEGF,12 and intravitreal anti-VEGF injections that reduce VEGF levels by binding between VEGF and the anti-VEGF agents in the eye.13 14 Intravitreal anti-VEGF injections in use include bevacizumab (off-label use),8 ranibizumab (EU approved drug)9 and aflibercept (off-label use; a phase III study is being conducted on this).15 16 Intravitreal injection therapy is becoming increasingly popular because it is simpler to perform and provides a faster treatment response than conventional laser therapy.17 18
The rate of disease progression in infants with ROP requiring treatment varies depending on the subtypes (type 1 ROP vs aggressive ROP) and location of lesions (zone I vs posterior zone II or zone II),19 20 so the effects of laser therapy and intravitreal injections may differ. Çömez et al21 reported that although intravitreal anti-VEGF injections were effective for aggressive ROP and type 1 ROP with zone I and posterior zone II lesion, additional treatment was required in many cases of aggressive ROP. Roohipoor et al22 reported that both laser therapy and anti-VEGF injection treatment were effective for type 1 ROP with zone II, but retreatment was lower with laser therapy.
In this study, Korean retinal specialists showed a tendency to choose anti-VEGF injection when ROP was located in zone I or posterior zone II and to select laser treatment when ROP was located in zone II. It has also been shown that anti-VEGF treatment is more frequently selected for aggressive ROP than for type 1 ROP. The reason is as follows: aggressive ROP is characterised by marked plus disease, no noticeable findings at the junction of vascular and avascular retina and a rapid progression of vascular abnormalities.21 23 24 Because the tempo of aggressive ROP is fast, anti-VEGF injection is more effective than laser therapy in lowering the high concentration of VEGF in the eye rapidly. Laser therapy has the advantage of reducing reactivation by destroying the avascular retina,25 but the wider the laser treatment area, the narrower the field of view. In particular, in the case of aggressive ROP, it may be difficult to determine the laser treatment range because the boundary between the avascular retina and vascular retina is not prominent.23 In addition, since PMA at the primary treatment for aggressive ROP is earlier than that for type 1 ROP, it seems that anti-VEGF injection therapy is preferable to laser therapy because premature infants have poor lung function and cannot tolerate general anaesthesia.
The appropriate injection dose and frequency of intravitreal anti-VEGF injections are controversial because of the risks of ocular and systemic exposure. The dose of bevacizumab administered in the BEAT-ROP study8 was 0.625 mg, which is half the adult dose. The RAINBOW study9 used ranibizumab 0.2 mg (equivalent to 40% of the clinically approved adult dose for age-related macular degeneration) and ranibizumab 0.1 mg. When it considers that the vitreous capacity of premature infants is approximately 1/4 that of adults, it can be considered a high dose.1 In age-related macular degeneration, the intravitreal half-life of bevacizumab was approximately 4.9–6.7 days, and its serum half-life was measured to be 11.3–18.7 days,26 while in ROP, the serum half-life of bevacizumab was 21 days on average, and serum bevacizumab was detected for more than 2 months.27 28 In the case of neovascular macular degeneration, the intravitreal half-life of ranibizumab was 9 days and its serum half-life was 2 hours.29 In ROP, the intravitreal half-life ranibizumab was as short as 5.6 days, and the serum half-life was 7.2 hours (0.3 days), which took longer than the case of macular degeneration.30 As a result, premature infants have a longer serum half-life of anti-VEGF agents than adults, so it takes longer for the VEGF concentration to return to normal. Since bevacizumab has an Fc domain, it takes time to remove, and its serum half-life is much longer than that of ranibizumab by about 20 days, which increases the risk of systemic exposure.31 When using anti-VEGF injections for the treatment of ROP, it is recommended to use a small dose of bevacizumab or a drug with a short serum half-life, such as ranibizumab.32 33 However, other aggressive ROP studies34–36 have used ranibizumab doses of 0.25–0.3 mg. Similarly, our study showed that although the dose of VEGF administered by retinal specialists varied, they tended to select higher doses for aggressive ROP than for type 1 ROP. Therefore, further studies are needed to determine the appropriate injection dose according to the subtype and lesion of ROP.
Reactivation of ROP usually occurs after anti-VEGF injection and rarely after laser treatment, with complete regression or incomplete regression of the original lesion.7 Reactivation phase proceeds in various ways from the demarcation line to the stage requiring treatment. However, reactivation is defined differently in the literature,37 and the degree of reactivation has been reported differently depending on the types and doses of therapeutic agents as well as the study period.38 39 In our study, treatment insufficiency and reactivation were classified based on 4 weeks before and after the first treatment.
Currently, there is no clear consensus on when and how to treat reactivation. Martínez-Castellanos et al40 proposed a treatment algorithm for treatment failure and reactivation of ROP after bevacizumab injection. They recommended that anti-VEGF injection should be repeated if new lesions above the ridge stage reappear or flat new blood vessels are observed at the advanced edge, and vitrectomy should be performed if vitreous traction is observed on the ridge lesion.
In this study, 52 eyes received secondary treatment for ROP reactivation, and no vitrectomy was performed in any case. Secondary treatment was required more frequently with anti-VEGF injections than with laser therapy, as well as more frequently with ranibizumab than with bevacizumab. It should be noted that the duration of additional treatment after primary treatment was shorter with bevacizumab than with ranibizumab. The reason is that although there are few cases, in the case of bevacizumab, laser ablation was performed if it was determined that additional treatment was needed within 2–6 weeks. There were no cases where the injection agent was administered more than three times, and there were no cases where another anti-VEGF agent was selected for reinjection. In all cases of the second injection, a higher dose than the first injection or the same dose as the first injection was selected. If the therapeutic effect was judged to be insufficient after two consecutive injections, laser treatment was performed. Based on our experience, laser treatment should be preferred if additional treatment is required, and it is not necessary to select a dose lower than the primary treatment when selecting anti-VEGF.
The limitation of this study include that the members of the Korean Retinopathy Society who participated in the study were informed of the standardised classification of ROP and plus disease, but the classification and treatment selection of ROP was based on individual judgement. In addition, the types and doses of anti-VEGF injections used in the study varied, and long-term follow-up and safety studies were lacking. Additional studies are needed more effective doses and frequencies of intravitreal anti-VEGF injections for ROP. However, this study presents data on the preference of anti-VEGF injection therapy as a primary treatment and as an additional treatment in a real clinical setting for ROP requiring treatment over the last 2 years. This is expected to be of great help to retinal specialists interested in anti-VEGF injections for ROP treatment.
In conclusion, this study is noteworthy in that it confirms the tendency to select intravitreal anti-VEGF injections or laser ablation according to the subtype of ROP and location of the lesion. It may also be helpful to come up with new guidelines for ROP treatment by understanding the tendency to opt for second-line treatment when reactivation occurs after injection. These findings suggest that ROP treatments are considered according to ROP subtype, location and reactivation in actual clinic situation.
This multicentre study was approved by the Institutional Review Board of participating hospitals: Keimyung University Dongsan Medical Center (DSMC 2021-08-076), Kyungpook National Hospital (KNUH 2022-02-021-002), Kyung Hee University Hospital (KHUH 2022-06-022), Yonsei University Severance Hospital (4-2022-0263), Inje University University Haeundae Paik Hospital (HPIRB 2022-07-026), Seoul National University Bundang Hospital (B-2111-720-303), Gyeongsang National University Hospital (GNUB 2022-06-016), Inje University University Ilsan Paik Hospital (ISPAIK 2022-03-023-001) and Ajou University School of Medicine (AJIRB-MED-20-508). Participants gave informed consent to participate in the study before taking part.
The authors would like to thank the members of the Korean Retinal Society for their interest and participation in this study.
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. Intravitreal aflibercept injection in Indian eyes with retinopathy of prematurity. Indian J Ophthalmol 2019;67:884–8. doi:10.4103/ijo.IJO_708_18
Ekinci DY,
Çelik K
. Comparison of the efficacy between intravitreal aflibercept and laser photocoagulation in the treatment of retinopathy of prematurity. J Pediatr Ophthalmol Strabismus 2020;57:54–60. doi:10.3928/01913913-20191104-01
Adams GGW,
Bunce C,
Xing W, et al
. Treatment trends for retinopathy of prematurity in the UK: active surveillance study of infants at risk. BMJ Open 2017;7:e013366. doi:10.1136/bmjopen-2016-013366
Prakalapakorn SG,
Greenberg L,
Edwards EM, et al
. Trends in retinopathy of prematurity screening and treatment: 2008-2018. Pediatrics 2021;147:e2020039966. doi:10.1542/peds.2020-039966
Fukushima Y,
Kawasaki R,
Sakaguchi H, et al
. Characterization of the progression pattern in retinopathy of prematurity subtypes. Ophthalmol Retina 2020;4:231–7. doi:10.1016/j.oret.2019.11.015
Shin DH,
Kong M,
. Risk factors and rate of progression for zone I versus zone II type 1 retinopathy of prematurity. J AAPOS 2014;18:124–8. doi:10.1016/j.jaapos.2013.12.003
Çömez A,
Karaküçük Y,
Özmen MC, et al
. The results of intravitreal bevacizumab monotherapy for treating aggressive posterior retinopathy of prematurity and type 1 retinopathy of prematurity. Eye (Lond) 2021;35:3302–10. doi:10.1038/s41433-021-01413-4
Roohipoor R,
Torabi H,
Karkhaneh R, et al
. Comparison of intravitreal bevacizumab injection and laser photocoagulation for type 1 zone II retinopathy of prematurity. J Curr Ophthalmol 2019;31:61–5. doi:10.1016/j.joco.2018.10.008
Kumawat D,
Sachan A,
Shah P, et al
. Aggressive posterior retinopathy of prematurity: a review on current understanding. Eye (Lond) 2021;35:1140–58. doi:10.1038/s41433-021-01392-6
Wang S-D,
Zhang G-M, Shenzhen Screening for Retinopathy of Prematurity Cooperative Group
. Laser therapy versus intravitreal injection of anti-VEGF agents in monotherapy of ROP: a meta-analysis. Int J Ophthalmol 2020;13:806–15. doi:10.18240/ijo.2020.05.17
Narnaware SH,
Bawankule PK,
Raje D
. Aggressive posterior retinopathy of prematurity (APROP): laser as the primary modality of treatment. J Ophthalmic Vis Res 2021;16:400–7. doi:10.18502/jovr.v16i3.9437
García-Quintanilla L,
Luaces-Rodríguez A,
Gil-Martínez M, et al
. Pharmacokinetics of intravitreal anti-VEGF drugs in age-related macular degeneration. Pharmaceutics 2019;11:365. doi:10.3390/pharmaceutics11080365
Kong L,
Bhatt AR,
Demny AB, et al
. Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity. Invest Ophthalmol Vis Sci 2015;56:956–61. doi:10.1167/iovs.14-15842
Hong YR,
Kim YH,
Kim SY, et al
. Plasma concentrations of vascular endothelial growth factor in retinopathy of prematurity after intravitreal bevacizumab injection. Retina 2015;35:1772–7. doi:10.1097/IAE.0000000000000535
Xu L,
Lu T,
Tuomi L, et al
. Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach. Invest Ophthalmol Vis Sci 2013;54:1616–24. doi:10.1167/iovs.12-10260
Fidler M,
Fleck BW,
Stahl A, et al
. Ranibizumab population pharmacokinetics and free VEGF pharmacodynamics in preterm infants with retinopathy of prematurity in the rainbow trial. Transl Vis Sci Technol 2020;9:43. doi:10.1167/tvst.9.8.43
Avery RL
. Bevacizumab (Avastin) for retinopathy of prematurity: wrong dose, wrong drug, or both? J AAPOS 2012;16:2–4. doi:10.1016/j.jaapos.2011.11.002
Wallace DK,
Kraker RT,
Freedman SF, et al
. Assessment of lower doses of intravitreous bevacizumab for retinopathy of prematurity: a phase 1 dosing study. JAMA Ophthalmol 2017;135:654–6. doi:10.1001/jamaophthalmol.2017.1055
Krohne TU,
Eter N, et al
. Comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity: a randomized clinical trial. JAMA Pediatr 2018;172:278–86. doi:10.1001/jamapediatrics.2017.4838
Sukgen EA,
Koçluk Y
. The vascularization process after intravitreal ranibizumab injections for aggressive posterior retinopathy of prematurity. Arq Bras Oftalmol 2017;80:30–4. doi:10.5935/0004-2749.20170009
Li X-J,
Yang X-P,
Sun S, et al
. Intravitreal ranibizumab for aggressive posterior retinopathy of prematurity. Chin Med J (Engl) 2016;129:2879–81. doi:10.4103/0366-6999.194638
Tong Q,
Yin H,
Zhao M, et al
. Outcomes and prognostic factors for aggressive posterior retinopathy of prematurity following initial treatment with intravitreal ranibizumab. BMC Ophthalmol 2018;18:150. doi:10.1186/s12886-018-0815-1
Valikodath NG,
Chan RVP
. Description and management of retinopathy of prematurity reactivation after intravitreal antivascular endothelial growth factor therapy. Curr Opin Ophthalmol 2021;32:468–74. doi:10.1097/ICU.0000000000000786
Patel SN,
Klufas MA
. Evidence to date: ranibizumab and its potential in the treatment of retinopathy of prematurity. Eye Brain 2019;11:25–35. doi:10.2147/EB.S189684
Reynolds JD,
Zhu Q, et al
. Time course of retinopathy of prematurity regression and reactivation after treatment with ranibizumab or laser in the rainbow trial. Ophthalmol Retina 2022;6:628–37. doi:10.1016/j.oret.2022.02.006
Martínez-Castellanos MA,
González-H León A,
Romo-Aguas JC, et al
. A proposal of an algorithm for the diagnosis and treatment of recurrence or treatment failure of retinopathy of prematurity after anti-VEGF therapy based on a large case series. Graefes Arch Clin Exp Ophthalmol 2020;258:767–72. doi:10.1007/s00417-020-04605-y
Contributors JJH has full access to the data and takes overall responsibility. Conception and design: JJH. Data collection: all authors. Writing of the manuscript: JJH. Guarantor, JJH.
Funding This study was supported by a research grand from The Korean Retina Society in 2020, and the National Research Foundation of Korea grant funded by the Korean government (Ministry of Science and ICT) (No. 2022RIG1A1011107).
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.


The Government's recent response to a major report on IP arrangements suggests Australia's intellectual property laws are about to change. So, what are the key proposed changes and what impact are they likely to have? We've put together an overview, together with five key takeaways for your organisation.
In June this year we examined the Productivity Commission's report on IP arrangements in Australia. The Government has now released its response to that report. As we anticipated, the Government supports, or supports in principle, many of the Productivity Commission's recommendations.
A summary of the Government's position on each recommendation is set out at the end of this article and we examine the impact of the Government's response to particular recommendations below.
IP Australia is already consulting in relation to a number of the proposed amendments to the Patents Act. Submissions can be made before 17 November 2017. Further consultations in relation to proposed changes to the Copyright Act will take place later this year and in the first half of 2018.
Users of the innovation patent system and companies that are considering enforcing patent rights should consider the merit of applying for innovation patents before the system is abolished.
Online service providers and rights holders should consider whether the proposed extension of the safe harbour scheme (which provides protection from copyright infringement) will impact on their business models.
Brand owners will need to act with greater vigilance to ensure that they are engaging in sufficient use of their registered trade marks so that those registrations are not at risk. The vulnerability of registrations will need to be considered every 3 years from the date the trade mark is filed.
Brand owners in the fashion and FMCG space will need to ensure that their distribution agreements clearly define any territorial restrictions and that they are complied with.
Pharmaceutical companies will need to ensure that they comply with the proposed new system for monitoring settlement agreements and that those agreements are not objectionable from a competition law perspective.
an interdepartmental policy group to support 'an integrated and coherent approach to developing the Government's policy agenda for IP issues'.
In our view, having a coherent and integrated approach to IP policy is a welcome step, not only to address the recommendations supported by the Government but also to help raise the profile of intellectual property laws in Australia.
the innovation patent system will be brought to end.
The changes to the inventive step test are unlikely to have a significant impact. The Commission's proposal is intended to clarify that a mere "scintilla" of invention is insufficient to establish an 'inventive step'. As the Law Council pointed out in its submission to the Commission, this proposal was based on a misunderstanding that Australian courts apply the "scintilla test" rather than the statutory one our courts do apply which asks whether the claimed invention is "obvious".
The abolition of the innovation patent system is a major reform. Australia has had a second tier patent system for low-level innovations since 1979. Users of the innovation patent system include local IT companies as well as companies in the gaming, transport and energy industries. Innovation patents have been a very powerful tool in litigation as they are granted quickly and are difficult to revoke.
A system for monitoring and mandatory reporting of settlement agreements between originator and generic pharmaceutical companies to detect 'pay for delay' agreements is supported in principle, with the Government stating that it would 'improve transparency and would equip the ACCC to detect any anti-competitive behaviour'.
The Government has suggested that a reporting scheme informed by the framework under the Corporations Act 2001 for Australian financial services licensees (AFSL) may be appropriate.
If the AFSL approach is adopted, the reporting scheme may require pharmaceutical companies to implement compliance programs to monitor and report pay for delay settlement agreements affecting Australian consumers, with penalties for a failure to report.
Innovative pharmaceutical and biotech companies will be relieved by the Government's decision not to implement the Commission's proposed changes to the extension of term regime for pharmaceutical patents, which would have severely limited the availability and length of extensions of patent term. Nevertheless, the Government hasn't ruled out other changes 'to improve the patent extension system'. We may therefore see rights to extension of term being curtailed in some other way.
to require the Trade Marks Office to challenge trade mark applications that contain contemporary geographical references.
In terms of the grace period, brand owners will need to be vigilant in ensuring that they use their marks quickly and across the full scope of the goods or services for which their marks are registered within three years from filing their applications. This change may assist in ensuring that marks which are not being used, do not present an obstacle to subsequent trade mark applications.
The second of these changes will remove any basis for brand owners to challenge the sale of genuine goods manufactured overseas but imported without the local trade mark owner's approval. The Government will engage in further consultation on exposure draft legislation.
As we predicted in June, the Government will finally take steps to repeal section 51(3) of the Competition and Consumer Act 2010 (Cth). Section 51(3) deals with the relationship between intellectual property and competition law.
If passed, a repeal of section 51(3), would bring some much needed clarity to that uneasy relationship, with the Government stating that 'where there is evidence of anti-competitive conduct associated with IP licensing arrangements, it is important that such conduct is appropriately regulated'. In practice, this would mean that IP transactions would no longer benefit from the limited exemptions under section 51(3) and would be subject to competition law, just like any other transaction.
The Productivity Commission recommended that the ACCC issue guidance on the application of Part IV of the Competition and Consumer Act 2010 (Cth) to intellectual property rights however the Government did not respond to that recommendation. We think that a repeal of section 51(3) will nonetheless give the ACCC sufficient motivation to release such guidance.
The Government also notes that, if anti-competitive conduct relating to intellectual property transactions is nonetheless in the public interest, the established ACCC authorisation process (which allows for arrangements that might otherwise contravene competition law to be authorised) is available under Part VII of the Competition and Consumer Act 2010 (Cth).
The recommendation made by the Productivity Commission, that Australia introduces a fair use exemption in lieu of the current and more restrictive fair dealing exemptions, received a lukewarm response from the Government, with it merely 'noting' the recommendation and stating that 'this is a complex issue and there are different approaches available to address it'.
The Government nonetheless intends to publicly consult on 'more flexible' copyright exemptions in early 2018 following the finalisation of other copyright reform priorities.


I used Denmay in Station RD a few years back. Nice people and the cost was considerably lower than the JLP.
Just gave them a ring before I saw this, as it happens.
I wonder if someone could give me so advice on which trades person and what this is.
So high up on my parents bedroom wall, where it meets the ceiling there is what looks like a damp/condensation patch.
So whats caused it and what needs to be done to fix it?
Could it be a leaking gutter?
If you are lucky it's just a full or loose gutter.
I've got a couple of customers who ignored the patches are they were infrequent. And then came the floods.
It could be a few broken tiles, or flashing, or the pointing, or wrong cement mix on the outside wall.
A friend, whose neighbour had built an attic extension, had more water was coming into the gutter, and overwhelming it. Could be lots of things.
I'd call a roofer first. Lots of them do their quotes on Saturdays so you may be lucky.
If you send a few texts tomorrow or emails tonight, you might be lucky and get a response.
Can anyone recommend a handyman/decorator who could sand a set of stairs and varnish them? The stairs are mostly done and probably only need a light sanding before they are varnished. TIA.
Angellic and colacubes like this.
This reminds me: there's probably quite a few local urban folks with all sorts of skills who may not look in this thread. Do people reckon a ''skill swap' thread (or something similar) would be worth a go?
clicker, Boudicca, brixtonblade and 1 other person like this.
Great idea but put in Community because there's a tax issue (it counts as income) which makes bartering tricky. And not just Brixton as I want to offer a free weekend in Bournemouth in exchange for help demolishing my greenhouse!
I'd be surprised if the taxman would trouble himself with trying to work out the identities of essentially anonymous posters!
Well yes, but I think that's why no-one has launched a barter site as HMRC might take an interest in the site (rather than individual posters).
Looking for a good optician locally or further afield.
The opticians on Coldharbour Lane/Electric Lane corner are good.
Thanks CC went there last time and I won't be returning.
I had a bad time with that little shop too sadly and ended up going to specsavers instead (where they did a more thorough eye test for much less money).
There's an "exotic" specialist over in sheen called CJ Hall - seemed quite good and have been given steroids and antibiotics to squeeze another couple of weeks out ot the old chap (and to confirm that he's not suffering ). I was pointed to them by streatham hill vets.
Mixed feedback on the coldharbour lane opticians.
Any other recommendations - perhaps in the Norwood / Streatham / Tulse Hill area?
Bloody auto correct. All the above should read opticians!!
I am looking for someone who can hang a door and do some general carpentry- type things (Nothing too difficult) for me next week. Does anyone have any recommendations?
In the end I went to Specsavers Streatham. Very thorough test, gave me my test results immediately,* happy with pricing and specs. Very busy shop but staff were cool and efficient. Didn't have a huge choice of frames for the lenses necessary but a far, far better experience than Clear Vision in Coldharbour Lane.
*which they should do under NHS regs. It took three follow up calls to CV for them to grudgingly send me a copy.
Banks Optometrists on Acre Lane (just opposite old Town Hall) are ultra-trustworthy on the medical/diagnostic side. Their selection of lenses and styles isn't particularly amazing though. But you can always get the test done there (where they'll do it properly), insist on a copy of your prescription, and then nip round to Specsavers on the High Street when it comes to spending money on actual specs. If you use contact lenses it's nearly always cheaper online these days anyway.
Can anyone recommend an alterations person who could fit a couple of zips into a pair of velvet seat cushions?
There's a woman in reliance arcade with a machine. She's great with clothes. I think she's Eritrean - anyway about 1/4 way down on left of coming from the high street.


It's not a blessing when mentally ill people die.
This is in response to xoJane's piece, "My Former Friend's Death Was A Blessing." You can also read about being a mental health ally and advocate as it relates to this piece here.
Earlier this week, my dad—someone with lifelong mental and physical health issues—tried to die by suicide and ended up in the ICU. He intentionally overdosed on his depression and anxiety medication. This was after several months of expressing suicidal thoughts to me and to therapists, and working with medical professionals in inpatient care.
About a month ago, my dad was refused any more inpatient care even though he insisted that he was still dealing with suicidal thoughts. He also received a denial letter for disability benefits, although he is dealing with early Alzheimer's, has had several surgeries for physical health problems, has been diagnosed with several serious mental illnesses, and has had worsening overall health since a car accident in October 2014.
Since then, he's been severely suicidal. Because he has a lifetime of mental health battles, including bipolar disorder and PTSD, this is not the first time I've worried about him attempting suicide. But it is the most upsetting time and it felt the most real. Over the last ten years or so, my dad has done nothing but try; this is his second serious attempt at getting the help he needs, including disability benefits and mental health care. In the last year or so, he's done nothing but try to fight for the resources he needs to survive, only to be failed time and time again.
Last month, doctors discovered a cyst on his breast while he was in the ER. When he later asked about getting it checked out, they repeated to him: "Are you here for your suicidal thoughts or for the cyst?" They refused to prioritize both; his physical health was put on the back burner because he was honest about wanting to die. Several times when he's been in the hospital, I've spoken with staff about his memory issues and cognitive health—all of which was ignored because they were focused on treating his depression. His symptoms of early Alzheimer's shouldn't be ignored, especially because some of his current medications make him even more drowsy and forgetful than he was before. He often forgets conversations we had just earlier in the week, and has had to be reminded about things we discussed. I've never been so angry with the health care system in my entire life.
This morning, I woke up after falling asleep crying about my dad's recent suicide attempt to find out about the now-removed xoJane essay, "My Former Friend's Death was a Blessing." I've never felt so angry at a writer. Yes, we're all entitled to our opinions, but some of those opinions should not be published, as Lisa Marie Basile details in her own piece about editorial integrity. I can only imagine how my dad, who feels useless and unworthy of life, would feel if he were to read that xoJane essay. It would be like a sign saying, "Because you can't take care of yourself right now, you're a burden to your family and friends, just like this writer says about her former friend. Your death would be a blessing, too."
Yes, we're all entitled to our opinions, but some of those opinions should not be published.
Those are thoughts suicidal people are already feeling. I know because my dad has told me. He loves me more than life itself, but he doesn't feel like he can do anything right. He feels like a burden to me and to others, and doesn't see any reason worth living anymore.
It hurts me so much to see that there are people out there who believe that someone like my dad, who can no longer take care of himself after over twenty years of fighting, are "beyond help" and that death is "inevitable." Just because someone deals with serious mental health issues doesn't mean we should give up hope and give them a reason to give up. It's not a blessing when mentally ill people die.
The individual situations are different, obviously. Leah was a young woman and she spoke of schizoaffective disorder. Unfortunately, we don't really know her. We know only of her what the writer chose to tell us through a voyeuristic, cold, empathy-free lens. My dad is middle-aged, physically disabled, and has a history of unhealthy coping mechanisms, like drinking and being a workaholic. But at their core, they're not so different. Neither could take care of themselves completely on their own, and both needed support. And in Leah's case, she failed to get that support, and even after her death, instead of being mourned, she was turned into a sensationalist headline.
Just because someone deals with serious mental health issues doesn't mean we should give up hope and give them a reason to give up.
My dad is mentally, physically, and cognitively ill right now. He needs help taking care of himself. He doesn't need self-care; he needs community support. It's not always an easy task, and for my own health and well being, I can't be all things to him at all times. But the one thing I can always do is reassure him—and any other mentally ill person reading this—that there is hope, and that they're loved. And they deserve to live, even when it may seem impossible.
Alaina Leary is a native Bostonian studying for her MA in Publishing at Emerson College, and working as a social content curator at Connelly Partners. Her work has been published in Cosmopolitan, Marie Claire, Seventeen, Redbook, BUST, Her Campus, AfterEllen, Ravishly, and more. When she's not busy playing around with words, she spends her time surrounded by her two cats, Blue and Gansey, or at the beach. She can often be found re-reading her favorite books and covering everything in glitter. You can find her on Twitter and Instagram @alainaskeys.


text:
Kościół Podwyższenia Krzyża Świętego w Falejówce − neogotycki kościół w Falejówce.

Historia
Kościół został wybudowany w latach 1908–1914, zaś końcowe prace przy nim zrealizowano w 1927. Według stanu z lutego 1939 kościół nie był jeszcze w pełni wykończony. Architektem był Wilhelm Szomek z Sanoka. Budynek został wzniesiony w stylu neogotyckim. W jego posiadaniu znajduje się kielich z 1. poł. XIX wieku posiadający ornamenty rokokowe.

W świątyni funkcjonuje parafia Podwyższenia Krzyża Świętego, utworzona 1927 roku. Poświęcenia dokonał ks. biskup Anatol Nowak.

Ks biskup Anatol Nowak opiekę duszpasterską powierzył księdzu Franciszkowi Witeszczakowi, który pracował wcześniej jako kapelan rezerwy Wojska Polskiego przy parafii Przemienienia Pańskiego w Sanoku. Kolejnyminymi proboszczami byli ks. Bronisław Stankiewicz i ks. Władysław Gwoździcki. Tuż przed rozpoczęciem II wojny światowej proboszczem w Falejówce został ks. Jan Matyja. Następnie parafią kierował ks. Tadeusz Cyran, a po nim od roku 1961 posługę kapłańską pełnił ks. Eugeniusz Raczkowski. W 1984 roku proboszczem został ks. Marian Bawłowicz. Kolejno - ks. Jan Klich. Od 1991 r. posługę kapłańską w tutejszej parafii pełni ks. Józef Joniec.

Przypisy

Zobacz też
 Lista zabytków w gminie Sanok w artykule "Wiki Lubi Zabytki"

Kościoły w archidiecezji przemyskiej
Świątynie pod wezwaniem Podwyższenia Krzyża Świętego
Kościół Podwyższenia Krzyża Świętego
Obiekty sakralne w gminie wiejskiej Sanok
Kościoły w powiecie sanockim
Architektura neogotycka w województwie podkarpackim
Budynki w Polsce oddane do użytku w 1914

redpajama_set_name: RedPajamaWikipedia


text:
Q: Any publicly available word dictionary in a text file? I am looking for a word dictionary for different languages(english, spanish, ...). However, almost all dictionaries that I could find are either provided by a program or on a website.
I want to get this word dictionary as a text file. (Also, this file should be publicly available.) Are there any public available word dictionaries in text files?

A: You can download the Wikitionary for off-line processing, instructions here in the FAQ:
https://en.wiktionary.org/wiki/Help:FAQ#Downloading_Wiktionary

A: If you're a Linux user, you can use one of the following files (depending on your distribution)

*

*/usr/share/dict/

*/var/lib/dict/

The GNU 'aspell' program makes use of this dictionary.

redpajama_set_name: RedPajamaStackExchange


1 potatoLemon juice from ½ a lemonArrangement Mix the potato in a blender, then include the lemon squeeze and blend once more. Apply the cover all over and rub delicately in roundabout movement, then abandon it to labor for 15-20 minutes and wash with warm water. Rehash the procedure consistently until you see the spots and stains vanish.
Soursop, or also known as Graviola, is the fruit of an evergreen tree native to Cuba, Mexico, the Caribbean Islands of Puerto Rico and Espanola, Central America and northern South America.
Its health benefits are widely popular throughout the world, and are connected to one of the deadliest diseases of our time – cancer. In fact, studies show that it is even more effective than chemotherapy.
The flesh of the fruit contains amazing properties. Its taste reminds of something between strawberries and pineapple, so it's definitely delicious. Each part of the plant is used for different purpose. Here, you will read when to use soursop and what its health benefits are.
According to some experts, soursop is even 1,000 times more effective than chemo in the treatment of cancer. What's more, anyone can afford it as it has an available price, which is not the case with the highly expensive chemotherapy.
Our skin is usually acidic. You should know that by restoring your skin's balance, this incredible apple cider vinegar toner helps your skin function normally, warding off bacteria and shedding dead skin cells at the proper rate so your skin remains healthy and your pores do not get clogged.
You will notice that your skin will be softer and you will have less itchy and dry red patches. With this recipe, you will have no more tiny pores on your nose.
– 3 tablespoons distilled or filtered water.
– 1 tablespoon organic raw Apple Cider Vinegar into a glass jar, container or bottle.
Put all the ingredients in a bottle and shake it to combine the mixture.
Apply the apple cider vinegar toner to your freshly cleansed skin using a pad or cotton ball, avoiding the eye area.
Apply your usual moisturizer after the toner has dried.
Store in a dry, cool, dark place.


To mark its 50th anniversary, the Ecole polytechnique fédérale de Lausanne (EPFL) gave free rein to three photographers, who were asked to capture the essence of the School and its future direction.Catherine Leutenegger delivers many detailed portraits of science, blurring the lines between the images she creates and those that she discovers and makes her own. Bogdan Konopka strips EPFL's buildings down to their still life form. And Olivier Christinat brings places to life by roaming the grounds and discreetly immersing himself in campus life.


text:
Estakhr, Mehdi
Mehdi Estakhr is a faculty in the Department of Humanities at Alabama State University where he teaches World History. He received his Ph.D. in History from UCLA. His diverse cultural exposure and academic background-grew up in Iran, Lebanon, Switzerland, and the USA; and graduated with a B.A. in Government, M.A. in Middle Eastern Studies, and a second M.A. and Ph.D. in European History-have widened the scope of his academic and research interests to include Comparative Religion, East-West Relations, and Early Modern World History.
Place of Zoroaster in History ( Two Book Set)
Europe's fascination with Zoroaster began in the classical period. Celebrated as the embodiment of wisdom and morality, and enjoying the prestige of an unfathomable antiquity, a personality cult, with validating authority, was created around him. This led several western schools of thought to claim him as their precursor and first master; foisting their own ideas under him to give them validity. When Zoroaster was metamorphed into an astrologer, his authority was also sought by those circles for which astrological occurences provided proof for claims they made, such as certain Neo-Platonists and Christians. Zoroaster's popularity culminated in the Renaissance when he was accredited with the so-called 'Zoroaster's Oracles,' - writings which provided the Humanist Platonists with the underpinningto construct their own passages to God independently of the divine revelation. In the post-Reformation religious controversies, Zoroaster was made to vouch for the truth of Christianity against the tide of freethinkers and atheists, and against Christian antagonists in the interdenominational conflict. The Enlightenment saw the Philosophes and their like minds enlist Zoroaster's authority to combat revelation and to advance the cause of 'Natural Religion'. Zoroaster' validating auhority continued to be exploited even after the arrival and the translation of the Avesta in France which shattered the image the West had made of him. Zoroaster's image as witness in the West provides a prime example of the use of the reconstructed imagined 'Other' for self-validation, self-criticism, as well as belaboring the 'Other'.

redpajama_set_name: RedPajamaCommonCrawl


If you ever experienced living in a country where hot and moist weather is common, then you're fully aware of the disastrous effects of humidity on your hair. It causes straight hair to frizz, perfect curls to drop and textured locks to be bushy. Luckily, you can now counteract these unfortunate results by simply keeping the following hair care tips in mind.
Moisturize Your Locks. If you're set to protect your strands against the effects of humid weather, then it's important that you keep your hair properly moisturized all the time. Remember that dehydrated hair tends to absorb moisture quickly, so ensure that you perform some deep conditioning to restore and nourish your damaged tresses.
Air Dry Your Hair. Although blow drying offers many benefits, it's not an ideal tool to use when dealing with a humid weather. Directing dry hot air at your strands will only dehydrated them further, and surely, dry hair is the last thing you'd want to have.
Wash With Cool Water. There's no better way to battle a hot weather than a good splash of cold water, so once you're done shampooing and conditioning your hair, rinse it off with a stream of cool water. This will help in closing down your hair's cuticle and sealing up your scalp's pores to keep the air's moisture from getting in and wrecking your hairstyle.
Apply Some Silicone Balm. When it comes to battling humidity, using a silicone-based hair balm can work wonders as it helps in sealing in your hair's natural moisture while preventing the air's dampness from interfering. Just make sure that you don't overload your hair with it though, since too much silicone can make your strands look heavy and lifeless.
Keep Your Hair Length. Although cutting off your hair can help you battle the sticky summer heat, it's not the best strategy to counteract the effects of humidity. If you want to prevent unwanted hair puffiness, then keep your current hair length. Cutting your hair short will only make your strands curl up in the damp air, leaving you a messy and an unattractive look.
Making your hair look healthy in a humid weather can be quite challenging, but by following these tips, you'll surely be able to maintain the beauty of your strands even with the dry air.


Whatever the brand and type of used car that is your target, choose the vehicle you want carefully. First check the specifications of the car from the information attached to the seller, both from online and offline advertisements. Production years, kilometers, transmissions, and prices need to be known.
If your heart is attached to one of the cars, don't forget to dig deeper into the seller. Generally in used car advertisements the name and number of the seller will be listed. Ask the history of the car in detail until you are absolutely sure.
One of the tricks of the seller is to install a low price specifically for credit to attract the attention of buyers. Before you come to see the car, make sure the price installed is valid for cash or credit.
Sometimes there are buyers who are lazy to compare one car to another. Though this can help to choose the best used car. Don't let you make the mistake of buying a used car this one Friend OtoSpector!
You certainly don't want to regret it when you bought a car, but there are similar vehicles that are better in condition and price? So, sort out some of the ideal car choices and record the specifications. After that, compare which car is superior and fits your criteria.
Don't forget too, use several online portals when comparing your chosen car. Not all sellers install their cars in all car sales portals. Therefore, if you compare across all portals, chances are you get a car with the best price and conditions.
Test drives are standard procedures that need to be done when buying a car, especially if the condition is used. Unfortunately not everyone can identify the signs of damage that occurs when the test drive is carried out.
As long as it can be driven comfortably, people immediately conclude that the car has no problem. Before doing a test drive, it would be better if you equip yourself with some basic knowledge about the condition of the car or even better ask your friends who understand about the car.
The time comes when you meet the used car seller. Generally, a buyer will check by asking questions and test drives to find out the condition of the car. Unfortunately there are still many who forget to check the service record (service record) of the car.
The mistake of buying a used car is often considered trivial but can affect a lot in the future. Through the record, you can find out whether the owner takes good care of his car or not. If the car is serviced periodically, then the condition will be good right? You don't need to worry!
If the service record of the car that you are going to buy is done in an authorized workshop, it's a good idea to cross-check the service data with the workshop. Make sure that there are improvements that still need to be done and periodic servicing is done regularly.
Not many people really understand the inner conditions of a car. Sometimes there are people who are not too familiar with cars but still desperate to buy a used car without doing a thorough check. The mistake of buying a used car this one will be fatal as a result if it is still done.
Do not hesitate to involve experts who are experienced in checking used cars to help you check thoroughly.


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You are here: Home / Press Releases / Bluewater Does a Glenn Beck Biog Comic
Bluewater Does a Glenn Beck Biog Comic
From the press release:
Bluewater Brings Glenn Beck's Success Story to Comics
From his roots as a teen disc jockey to his position of influence today, Glenn Beck has taken an amazing journey through the world of the mass media. As a commentator and host on FOX News Channel and as the broadcaster behind his own nationally syndicated talk-radio show, Beck has become a leading voice of the country's Conservative and Evangelical movements.
Now Beck is taking yet another leap: He's set to star in his won biography comic from independent comics company Bluewater Productions.
Political Power: Glenn Beck will hit comic shops and online retailers in February. The 32-page comic retails for $3.99.
Jerome Maida, a frequent author of Bluewater's bio comics, wrote the script for Political Power: Glenn Beck. Mark Sparacio, a veteran artist who has worked with both Marvel Comics and DC Comics, provided the cover art for this comic. The interior art is being done by Aleksandar Bozic who also worked on the "Political Power: Bill O'Reilly" comic book.
Maida said that Beck was an "irresistible figure to write".
"We all know how successful, powerful and influential he is today. What I was interested in was what made him that way", said Maida. "Here is someone who was so supremely talented he was working in radio and winning fans since he was 13. At the same time, he has had a very troubled and tragic life. So it was fascinating detailing how he overcame that to get to where he is today."
"It's not a typical sad story because in the end the bio reveals that the prevailing theme in Glenn's life is redemption. Which I feel those on either side of the political aisle will find compelling", said Maida.
Bluewater president and founder Darren Davis said that Beck is the perfect subject for a comic biography: He's a figure who's risen from obscurity to challenge such talk-show icons as Rush Limbaugh and Bill O'Reilly for media supremacy.
"We try to focus on figures that bring out a lot of passion for our biographies," Davis said. "Glenn Beck certainly does that. Whether you like his politics or you find them reprehensible, you most certainly have an opinion about him. I'm sure a lot of readers will want to know how the Glenn Beck surge got its start. This comic will show them."
Bluewater's biography comics have been covered by such mainstream media outlets as the Washington Post, New York Times and Forbes Magazine. By covering such celebrities and political leaders as Lady Gaga, Angelina Jolie, Sarah Palin and Facebook founder Mark Zuckerberg, Bluewater is bringing new readers to the comics world.
The company produces three lines of biography comics: Female Force, Political Power and Fame. Each line has produced comics that have sold out of their original runs at a time in which independent comics companies are struggling to gain an audience.
To pre-order the "Political Power: Glenn Beck" comic go to your local comic book store or you can order it online at TFAW here http://bit.ly/e2VaJH
In stores in January is "Political Power: Bill O'Reilly" and can be pre-ordered here: http://bit.ly/fACXsS
Bluewater also produces a wide range of fiction titles, everything from superhero stories to horror, young-adult and science fiction titles.
For more information about Bluewater, visit the company's Web site at http://www.bluewaterprod.com/
Beyonce Gets a Bluewater Biog Comic
OMFG! Bluewater Releases a Justin Bieber Biog Comic! The End of Comics is Nigh!
Bluewater Releases Pink Floyd and Led Zeppelin Biog Comics
Sarah Palin Returns to Bluewater's Pages in New Comic Book
Adam West Partners with Bluewater for New Comic Series
Posted by Edward Kaye on Wednesday, December 8, 2021 at 12:55 am
Filed under Press Releases · Tagged with Bluewater


Found 87 tutors in Tangent, OR 97389 – page 3 of 9.
I used to tutor back in high school under a similar system, but through the school. It was senior year when I would travel to student's homes for 5 different students, usually in math.
I LOVE teaching English as a second language. I love working with international students. It doesn't matter why you want to study English; I will find a way to make you have a wonderful experience.


Ocwen Servicing Abuses in Maryland and Elsewhere: Foreclosures Spark Lawsky Investigation and Lawsuits | The Holland Law Firm, P.C.
When taken all together, these fees were not small. In fact, Ocwen claims the couple now owes more than they borrowed in the first place. They borrowed $98,000. But an Ocwen bill cited in the lawsuit claims the couple now owes $150,000 despite a decade of making their mortgage payments.
The story shows Ocwen charging fees completely unrelated to the original problem: force-placed insurance (even though the homeowners kept current home insurance) and "property restoration" fees. When the homeowners tried to talk to Ocwen about the problem, their calls went to a call center abroad. The call center staff were not equipped to answer any of their questions or fix the problem.
The Florida lawsuit is far from the first time Ocwen has been in trouble. Less than a year earlier, in December 2013, Ocwen settled a national lawsuit with federal regulators and State Attorneys General, agreeing to change its ways and give billions of dollars in relief and compensation to homeowners. But already, Ocwen is subject to regulatory investigation. The New York Department of Financial Services is investigating several aspects of Ocwen's business.
First, the Department is investigating Ocwen's dealings with a company called Altisource. The Department alleged in a letter to Ocwen in August 2014, that Ocwen was channeling money to Altisource for nominal services, and that Ocwen was not honest with its investors about the relationship with Altisource. Following the Department's letter, a group of investors filed a suit against Ocwen, reported here.


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Football World Cup 2022 in Qatar: real and false concerns
Tag 27 in Doha. And when you stroll out of the hotel that morning with your World Cup accreditation around...
Journalists complain about interference in reporting
Wa few days before the start of the soccer World Cup in Qatar local journalists feel restricted by their right...
Qatar: Security forces harass Danish TV team
Chad crisis: anger against those in power
Dhe photo says more than any official statement: The American Ambassador in Chad kneels next to bloodstains on a street...
Settlers attack Israeli army
In Israel raises concerns about escalating violence by Jewish settlers West Bank to. The reason is that the attacks in...
Border police officer killed in attack on checkpoint
uJust before the Jewish holiday of Sukkot, tensions in the Israeli-occupied territories have continued to rise. In an attack on...
Security forces in Iran beat up elite university
IAccording to local media reports, security forces in the Iranian capital Tehran used violence against students. Police officers and militias...
Ousted President Damiba gives up
How big is his support in Burkina Faso? Coup leader Ibrahima Traoré is celebrating in Ouagadougou on Sunday. Image: Reuters...
Protesters in Burkina Faso attack the French embassy
Nafter the coup in West Africa Burkina Faso French institutions have become the target of sometimes violent protests. Dozens of...
Iran Human Rights counts at least 83 dead in protests
Dhe protests in Iran after the death of 22-year-old Mahsa Amini, who was arrested by the vice squad, are now...
Rocket Attacks on Iraq's Green Zone
Supporters of influential Shia cleric Muqtada al-Sadr clashed with police during a demonstration on September 28 on the Jumhuriya Bridge...
Israeli security forces kill two Palestinians
A car shot after an Israeli raid in Nablus Image: Reuters Israeli police said emergency forces were shot at while...
Sri Lanka gives orders to shoot
NAfter two chaotic and violent days and nights, the situation in Sri Lanka remains tense. The Ministry of Defense has...
After attack in Tel Aviv: Suspected assassin shot dead
Nfter the deadly attack in the center of the Israeli coastal metropolis of Tel Aviv, the suspected assassin was shot...
Verdi is calling for warning strikes at six airports on Monday
The hourly wage for security guards in passenger control is to increase by at least one euro. Image: dpa Among...


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Q: Joomla 3.0.4 - not able to login to administrator I downloaded the files and database from the production server to my local machine and have been able to connect them, which displays a working website.
I tried logging into the admin but wasn't able to do so. The site gets redirected to domain.com/index.php
I later found out the error:
echo $this->baseurl;
This statement should return domain.com/administrator but only returns domain.com.. This causes the form to post the login value as only index.php instead of administrator/index.php..
For the interim, I did a browser hack to access the admin panel. How do I fix this globally?

A: After some analysis found out that in configuration.php there is a variable called as $live_site which needs to be set to blank (public $live_site = ''; ). If set to something else  then the above problem occurs.


How Do the 2018 Chevrolet Equinox Reviews Stack Up to the Competition?
The Chevy Equinox recently underwent a full redesign, providing Aurora, IL shoppers access to exciting features like a diesel engine, upgraded infotainment, and more. While the critics have always praised the crossover, we wondered how this refresh would impact the 2018 Chevrolet Equinox reviews and how well it would hold up against competitor vehicles, some of whom also received upgraded equipment. To answer that, we scoured the web and compared the expert reviews of the Equinox with its chief rivals; the Kia Sportage, the Toyota RAV4, and the Jeep Compass. Read on to see how Chevrolet's compact crossover compares, then drop drive by Chevrolet of Naperville to see if you don't agree; it's still one of the best CUVs you can buy for the money.
Go beyond the 2018 Chevrolet Equinox reviews when you schedule an Aurora test drive and decide for yourself. Contact Chevrolet of Naperville at 630-357-6100 or stop by our showroom at 1515 West Ogden Ave. in Naperville, IL to get started.
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Fourth Genre: Explorations in Nonfiction is devoted to publishing notable, innovative work in nonfiction. The title reflects the intention to give nonfiction its due as a literary genre to give writers of the fourth genre a showcase for their work and to give readers a place to find the liveliest and most creative works in the form. To reflect the genre's flexibility and expansiveness, the journal includes works ranging from personal essays and memoirs to literary journalism and personal criticism.
Copyright © Michigan State University Press.


Pots are the perfect way to add greenery and colour to paved outdoor spaces and balconies. Depending on the space you have, large pots accommodate small trees, which are great for shade. Large pots look best when layered in groups with smaller ones, creating interesting layers. For very small areas, plants in pots can sit on shelves, tables or securely attach to handrails, and there are many cost-effective vertical garden systems in your local nursery of hardware store (you know I LOVE supporting local businesses).
Choose pots of varying heights – and don't forget vertical gardens.
It's important you choose furniture that fits the scale of your outdoor area, and takes into account the number of people you'll be regularly accommodating. You can more easily add extra guests to a round table than to a square one, however a rectangular table will pair well with a bench. Armchairs, long chairs and benches can be added to create separate seating and relaxing areas, but don't overcrowd the space.
Offer a variety of seating, preferably in separate zones.
The size of your outdoor area will dictate the size of your plants. Be careful to choose the right kind of tree, as roots can damage the surrounding area and maybe even the foundations of your home. Native trees are generally bullet-proof in our climate and can survive very dry times. A deciduous plant, however, provides the dual benefit of shading you from the strong sun and heat in summer, and allowing warmth through when the leaves fall in winter.
You can more easily add extra guests to a round table than to a square one.
Since plants actively start to grow around spring, now is a really good time to repot plants that have outgrown their original pot. Flowering plants are mostly seasonal and should be planted asap as these will bloom and expand at the first hint of spring. For the best result, layer these against green and leafy plants, or add them to a wall or hang from ceiling baskets.
Mulch looks great and helps protects plants.
On paved areas, trees will benefit from large openings in the ground to allow enough water through. Edging looks neat and will help keep the soil from being washed out. Short bushes will define the areas and soften the hard appearance of paved surfaces. And don't forget the power of mulch: it looks and smells great, adds nutrients back into the ground, and most importantly, it provides a protective layer to keep moisture in and around the plants, saving the amount of water you need to use.
On hot days you'll want to go outdoors to sit in the shade and enjoy the breeze. Perfect for a relaxing snooze, reading a book or sipping a drink with friends, the canopy of a large tree will offer shade and that uplifting contact with nature. Umbrellas, sails and cane canopies are all shade options to consider.
Lounging and eating areas need shade.
Can you add a water feature or bird bath? This helps with cooling down the area, and the soothing sound of water adds another relaxing element to your outdoor experience. It also attracts birds. Scatter around colourful cushions, add lighting, candles… if it's truly an "outdoor room" then you need to make it as inviting as possible.


NZD 98,550 ? LKR 11,559,882Program fees are indicative only. Speak to your IDP study counsellor to get up-to-date course prices.
GBP 14,000 ? LKR 3,185,961Program fees are indicative only. Speak to your IDP study counsellor to get up-to-date course prices.
GBP 50,550 ? LKR 11,503,596Program fees are indicative only. Speak to your IDP study counsellor to get up-to-date course prices.
AUD 35,600 ? LKR 4,456,158Program fees are indicative only. Speak to your IDP study counsellor to get up-to-date course prices.
AUD 76,800 ? LKR 9,613,284Program fees are indicative only. Speak to your IDP study counsellor to get up-to-date course prices.
AUD 144,000 ? LKR 18,024,908Program fees are indicative only. Speak to your IDP study counsellor to get up-to-date course prices.
AUD 148,800 ? LKR 18,625,738Program fees are indicative only. Speak to your IDP study counsellor to get up-to-date course prices.


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Shannon Storms Beador
Gina Kirschenheiter
Emily Simpson
Returning for Season 14 are Housewives: Tamra Judge, Shannon Storms Beador, Kelly Dodd, Gina Kirschenheiter, and Emily Simpson. The ladies are joined by new housewife Braunwyn Windham-Burke. The tres amigas are back with their número uno, the OG of the OC, Vicki Gunvalson, who appears throughout the season. Tamra is moving on up, as she settles into her new home behind the gates of the neighborhood that started it all, Coto de Caza. With Eddie's heart condition on the mend, she finds herself nursing the relationships around her as she is caught in the middle, not only at home with her two sons Ryan and Spencer arguing over their beliefs, but also with Vicki and Kelly, who both refuse to back down. Having shed over 40 pounds and the baggage of her marriage, Shannon is back on the fun bus as she juggles her many suitors. It's her year of transformation, as she tightens and lightens and does her best to avoid the negativity around her. After enjoying her short stint of the single life, Kelly has ditched her "bench" in favor of her new boyfriend, Dr. Brian, a plastic surgeon. Still reeling from the accusations at last year's reunion, more shocking allegations are spread about Kelly causing her to reassess how she deals with anger. Powering her way through a difficult year, Gina leans on the ladies more than ever as she opens up about her heartache and mistakes. She finds an unlikely ally in the group as her other friendships are put to the test. With Shane busy studying for the California Bar exam, Emily carries the full load of her home life, functioning as a single mother to her three young kids and step kids. As Emily and her husband approach their 10 years of marriage, his absence weighs on her, overshadowing their landmark anniversary. Brought into the group through Kelly, new housewife Braunwyn is a mother of seven with a full house including a baby, toddler, twin kindergarteners, and three teenagers. When she is not escaping to her love shack with husband Sean, Braunwyn is always ready for a mom's night out as she gets to know these OC ladies in more ways than one. Vicki finds herself in the hot seat once again after hopping on the rumor mill train. But she doesn't let that detour her way to happiness as her love tank is full when Steve finally pops the question that she has been eager to hear.


We're on the look out for an awesome web developer who would like to join the Puddle ranks. You will have 5+ years in the industry. You'll love working in PHP, MySQL, CSS and HTML, and you'll also be a demon on WordPress, Joomla, Magento and Shopify. You'll also live fairly close to the office, we're not a fan of big commutes. Interested? drop us an email at [email protected].


As tomorrow is Halloween, this week's blog is exploring Charlotte Perkins Gilman's short story "The Yellow Wallpaper," the horrifying tale of a woman who slowly goes insane under the "rest cure" prescribed by her doctor and enforced by her husband. As a short story that I love to teach, I wanted to examine if digital tools allow us to interpret the text in different ways, and whether or not that interpretation added to our understanding of the story and its context.
omitted. As with most stories, the ending is, well, kind of important, so that was unfortunate. Using the text available, though, I pasted the plain text version into Voyant Tools, a "web-based reading and analysis environment for digital texts" that allows the user to view a word cloud of the most frequently used terms, average words per sentence, most-used words in context, and the relative frequency of words in different document segments. So, how would this be useful, you ask? Well, because while we often focus on the "close read" of documents in our classrooms, we also know the importance of looking at texts in their larger historical context. Voyant allows us to analyze these larger historical trends through the frequency of certain words used and comparing them across texts.
Maupassant's French classic. Even for non-French-speakers, one could define the few words that show up in the word cloud and compare them against others works from the same time. While this tool certainly has the potential to open up digital texts for study and comparison, there didn't seem to be a way to filter your search, and knowing that "said" or "he" were the most frequently used words may not be particularly useful in every textual analysis. In "The Yellow Wallpaper," though, an early feminist work, it is quite important that this story, told from the point of view of a woman, is dominated with "John said"s, so, in that way, it could be a helpful teaching tool.
French). If one of the goals of such tools is to provide a broader view of the language in digital texts, this seems like it would have been a useful feature.


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Orlistat, Alli and Xenical
The only over-the-counter drug for weight loss that has been approved by the FDA is being
reviewed by the agency after reports suggested the drug, orlistat, may cause liver damage. [1]
More than 30 reports to FDA said that patients taking Alli and Xenical. Xenical is the
prescription form of the pill. Many wound up hospitalized for their condition, while six patients
were treated for liver failure. [1]
Glaxo sells the nonprescription version under the brand name alli. The company said in a
statement "there is no evidence that alli causes liver damage," which can stem from many
causes. People who are overweight or obese are predisposed to liver-related disorders, the
company said. [2]
Alli (Orlistat 60 mg Capsules)
Claim: Weight Loss Aid
Typically, enzymes in your intestines break down fat from food so your body can absorb the fat.
But the active ingredient in alli attacks to some of these enzymes and prevents them from
digesting about a quarter of the fat you eat. Because undigested fat can't be absorbed, it
passes out of your body instead of turning into calories.
Common Side Effects: The oily stuff sticks to your toilet; it is hard to clean. In addition, if you
intake a lot of grease food, you may experience an urgent need to go to bathroom. It can prove
potentially embarrassing and uncomfortable; some oily bowel may leak out. Even though Alli is
specifically structured to take out the fatty content of dietary intake, It may also prevent the
absorption of fat-soluble vitamins.
Good thing is.. because of the embarrassing situation and the urgent needs to go to bathroom,
most of the users become self-motivated to cut out the fatty diets.
Patients should not use alli if they are pregnant or breast-feeding, have had an organ transplant
or taking medicines to prevent rejections, have problems absorbing food, or are not overweight.
[1] Health Buzz: Weight-Loss Drug Faces FDA Review and Other Health News U.S. News
[2] U.S. Probes Roche, Glaxo Diet Drug Over Liver Injury ABC News, August 24, 3009.


There are a number of top attorneys on our free Springfield bankruptcy lawyers list who will help consumers to put a stop to creditor harassment and so they can get on with their lives.
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Pornhub has revealed the most popular search terms of the region.
Pornhub has revealed what Mancunian's like to search on their site, and their results might surprise you.
According to the Manchester Evening News, the adult website released exclusive data which showed people in Manchester used search terms which included Liverpool more than anywhere else in the UK.
"Liverpool girls" was searched for 120 per cent more on average than the rest of the UK, while other Merseyside-based terms popular among Mancunians were "Scally" with 113 per cent more searches, "Scouse," with 105 percent more searches and "Liverpool" with 97 percent more searches.
According to their data, people from Birmingham spent the most time watching videos, followed by Sheffield and Leeds.
Pornhub also found that people in Manchester lasted seven seconds longer on the site than the UK average of nine minutes and 18 seconds.