_:b416004037 . _:b416004017 . _:b6199388 . _:b416003965 "5"^^ . _:b416004072 . _:b416004113 . _:b416003964 "7"^^ . _:b416004112 . _:b6199390 . _:b416003967 "5"^^ . _:b416004057 . _:b416004115 . _:b416003966 "5"^^ . . _:b416004114 . _:b416003962 "10"^^ . . _:b416003963 "7"^^ . . . . . _:b416003961 "10"^^ . _:b416004050 . _:b416003997 . _:b416003960 "10"^^ . _:b6199382 "For many cancer types, there has been a parallel improvement in prognosis (Lin and Winer, 2007; Vora and Reckamp, >>2008<<), likely in part because of the earlier detection of indolent tumours (Cancer Incidence in Sweden, 2007), but also because of the introduction of more effective treatment." . _:b416003973 "4"^^ . _:b416003972 "4"^^ . . . . _:b416003975 "4"^^ . _:b416003974 "4"^^ . _:b416003969 "4"^^ . _:b416004054 . _:b416003968 "4"^^ . _:b416003971 "4"^^ . . _:b416003962 . _:b416003970 "4"^^ . . _:b416003981 "3"^^ . _:b416003980 "3"^^ . _:b416003983 "3"^^ . _:b416004030 . . _:b416003982 "3"^^ . _:b416004079 . _:b416003996 . . _:b416003977 "4"^^ . _:b416004059 . _:b416003976 "4"^^ . . _:b416004099 . _:b416003979 "3"^^ . _:b416003967 . _:b416004067 . _:b416003978 "4"^^ . _:b416003989 "3"^^ . _:b416004026 . _:b416003988 "3"^^ . _:b416003994 . _:b416003991 "3"^^ . . _:b416003981 . _:b416003990 "3"^^ . _:b416003985 "3"^^ . _:b416003984 "3"^^ . _:b416004074 . _:b416004009 . _:b416003987 "3"^^ . _:b416003986 "3"^^ . . _:b416004024 . _:b416003997 "3"^^ . . _:b416003996 "3"^^ . _:b6199385 . _:b416003999 "3"^^ . _:b416004093 . _:b416004068 . _:b416003998 "3"^^ . _:b416003973 . _:b416003993 "3"^^ . _:b416004106 . _:b416003992 "3"^^ . . _:b416004116 . _:b416003995 "3"^^ . . _:b416003994 "3"^^ . _:b416004005 "2"^^ . . _:b416004004 "2"^^ . . . _:b416004007 "2"^^ . _:b416004006 "2"^^ . . . _:b416004001 "3"^^ . . _:b416004000 "3"^^ . . _:b416003977 . _:b416004003 "3"^^ . . _:b416004002 "3"^^ . _:b416004110 . _:b416004013 "2"^^ . _:b416004056 . _:b416004012 "2"^^ . . _:b6199389 "A reported improvement in the short-term survival (Slotman et al, 2007; Vora and Reckamp, >>2008<<) may therefore, together with a presumed inefficiency of systemic therapy beyond the blood\u2013brain barrier (Slotman et al, 2007), constitute important prerequisites for the increased numbers of lung cancer patients admitted with BM of both" . _:b6199392 "The reported incidence of BM among women diagnosed with breast cancer ranges from 5 to 20% (Schouten et al, >>2002<<; Barnholtz-Sloan et al, 2004)." . _:b416004015 "2"^^ . . _:b416004014 "2"^^ . _:b416004009 "2"^^ . . _:b416004008 "2"^^ . _:b416004027 . _:b416004011 "2"^^ . _:b416004015 . _:b416004103 . _:b416004010 "2"^^ . _:b416004021 "2"^^ . . _:b416004020 "2"^^ . _:b416004007 . _:b416004086 . _:b416004023 "2"^^ . . _:b416003983 . _:b416004022 "2"^^ . _:b416004017 "2"^^ . _:b416004016 "2"^^ . _:b416004107 . . _:b6199384 "Brain metastases are a common event in lung cancer, observed in 10\u201320% of patients screened at diagnosis of a non-small-cell lung cancer (Gavrilovic and Posner, >>2005<<), and even more frequently in small-cell lung cancer patients (Castrucci and Knisely, 2008)." . _:b416003984 . _:b416004019 "2"^^ . . _:b416004083 . _:b416004018 "2"^^ . _:b416004091 . . . _:b416004046 . _:b6199404 "In a US study of patients with BM from renal cell carcinoma (Shuch et al, >>2008<<), 1-year survival was, however, 48%." . _:b416003988 . _:b416004029 "2"^^ . _:b416003972 . _:b416004028 "2"^^ . _:b416004111 . _:b416003999 . _:b416004031 "2"^^ . _:b416004030 "2"^^ . _:b416004013 . _:b416004025 "2"^^ . _:b416004087 . _:b416004024 "2"^^ . _:b416004108 . . _:b416004027 "2"^^ . _:b416004026 "2"^^ . _:b416004023 . _:b416004037 "2"^^ . . _:b6199403 . _:b416004036 "2"^^ . _:b416004094 . _:b416004039 "2"^^ . _:b416004010 . _:b416004038 "2"^^ . . _:b416004033 "2"^^ . _:b6199387 "With time from lung cancer diagnosis, the proportion of patients developing BM increases rapidly (Mujoomdar et al, 2007; Slotman et al, >>2007<<). A reported improvement in the short-term survival (Slotman et al, 2007; Vora and Reckamp, 2008) may therefore, together with a presumed inefficiency of systemic therapy beyond the blood\u2013brain barrier (Slotman et al, 2007), constitute" . . . . _:b416004113 . _:b416004032 "2"^^ . _:b416004035 "2"^^ . _:b416004034 "2"^^ . _:b416004080 . _:b6199401 . _:b416004045 "2"^^ . _:b416003985 . _:b416004044 "2"^^ . . _:b416004047 "2"^^ . _:b6199385 "are a common event in lung cancer, observed in 10\u201320% of patients screened at diagnosis of a non-small-cell lung cancer (Gavrilovic and Posner, 2005), and even more frequently in small-cell lung cancer patients (Castrucci and Knisely, >>2008<<). With time from lung cancer diagnosis, the proportion of patients developing BM increases rapidly (Mujoomdar et al, 2007; Slotman et al, 2007)." . . _:b6199402 . _:b416004046 "2"^^ . . _:b416004069 . . _:b416004041 "2"^^ . . . _:b416004102 . _:b416004040 "2"^^ . . . . _:b416004043 "2"^^ . . _:b416004042 "2"^^ . "PMC0" . . . _:b6199393 . _:b416004053 "2"^^ . _:b6199402 "The highest 1-year survival proportions, around 20%, were observed for patients with kidney, breast or prostate cancer, which is in line with previous reports for breast cancer (Palmieri et al, >>2006<<; Altundag et al, 2007), whereas studies for prostate cancer are scarce." . _:b416004052 "2"^^ . . _:b416004065 . . _:b416004055 "2"^^ . _:b416004078 . _:b6199394 . _:b416004054 "2"^^ . _:b6199383 "incidence rates of lung cancer in many Western countries, including Sweden, have stabilized and even decreased in recent years among men, whereas an increasing trend is still evident among women (Cancer Incidence in Sweden, 2007; Toh, >>2009<<). Brain metastases are a common event in lung cancer, observed in 10\u201320% of patients screened at diagnosis of a non-small-cell lung cancer (Gavrilovic and Posner, 2005), and even more frequently in small-cell lung cancer patients" . _:b416004049 "2"^^ . . . _:b416004048 "2"^^ . _:b416004051 "2"^^ . _:b416004050 "2"^^ . _:b416004061 "2"^^ . _:b416003980 . _:b6199396 . _:b416004060 "2"^^ . . _:b416004063 "2"^^ . _:b416004115 . _:b416004062 "2"^^ . _:b416003965 . _:b416004057 "2"^^ . . . _:b416004000 . _:b416003964 . _:b416004056 "2"^^ . _:b416004076 . _:b416003967 . _:b416004059 "2"^^ . . . _:b416003966 . _:b416004058 "2"^^ . _:b416004039 . _:b6199380 . _:b416003961 . _:b416004069 "2"^^ . _:b416003960 . _:b416004068 "2"^^ . _:b416003963 . _:b416004071 "2"^^ . _:b416003962 . . _:b416004070 "2"^^ . . _:b416003973 . _:b416004065 "2"^^ . . _:b416003972 . _:b6199393 "The reported incidence of BM among women diagnosed with breast cancer ranges from 5 to 20% (Schouten et al, 2002; Barnholtz-Sloan et al, >>2004<<). Characteristics repeatedly associated with an increased BM risk include young age, oestrogen receptor-negative tumours and advanced stage at primary diagnosis (Palmieri et al, 2006; Lin and Winer, 2007), whereas the potential predictive" . _:b416004064 "2"^^ . . _:b416003975 . _:b416004067 "2"^^ . . _:b416003974 . . _:b416004066 "2"^^ . _:b416003969 . _:b6199386 . _:b416004077 "2"^^ . _:b416003968 . _:b416004076 "2"^^ . _:b416003971 . _:b416004096 . _:b416003995 . _:b416003992 . _:b416004079 "2"^^ . . _:b416003970 . _:b416004078 "2"^^ . . _:b416003981 . _:b416004073 "2"^^ . _:b416003980 . _:b416004072 "2"^^ . _:b416003983 . _:b416004075 "2"^^ . _:b416003982 . . _:b416004074 "2"^^ . _:b416003977 . _:b416004085 "2"^^ . _:b416004058 . _:b416003976 . _:b416004084 "2"^^ . _:b6199405 "Our data give important information about an expanding group of patients with a significant need for supportive care and thus generating high health-care costs (Taillibert and Delattre, >>2005<<). The study was, however, limited to patients hospitalised with BM. Although it is feasible to believe that the majority of patients diagnosed with BM are hospitalised at some point during the disease course, our cohort most likely" . . _:b416003979 . _:b416004087 "2"^^ . . . _:b416003978 . _:b416004086 "2"^^ . _:b416003989 . _:b416004081 "2"^^ . . _:b416003988 . _:b416004080 "2"^^ . _:b416004112 . _:b416004040 . _:b416003991 . _:b416004083 "2"^^ . . . _:b416003990 . _:b416004082 "2"^^ . _:b416004084 . . _:b416003985 . _:b416004018 . _:b416004093 "2"^^ . . _:b416003984 . _:b6199378 "The NCR was established in 1958 and is estimated to be >95% complete overall, with some variation by primary cancer type (Barlow et al, >>2009<<). We initially identified 16\u2009175 patients admitted with BM in the NPR. However, following matching with the NCR, we excluded 445 patients who were concomitantly registered with a primary brain tumour. We also excluded 213 individuals with" . _:b416004092 "2"^^ . _:b416004082 . _:b416003987 . _:b6199380 . _:b416004095 "2"^^ . _:b416004101 . _:b416003986 . _:b6199381 . _:b416004094 "2"^^ . _:b6199404 . _:b416003991 . . _:b6199382 . _:b416003997 . _:b416004089 "2"^^ . _:b6199377 "materials and methods" . _:b6199383 . _:b416003996 . _:b416004088 "2"^^ . _:b416004044 . . _:b416003999 . _:b416004091 "2"^^ . _:b416003998 . _:b416004085 . _:b416004055 . _:b416004090 "2"^^ . _:b6199377 . _:b6199388 "With time from lung cancer diagnosis, the proportion of patients developing BM increases rapidly (Mujoomdar et al, 2007; Slotman et al, 2007). A reported improvement in the short-term survival (Slotman et al, >>2007<<; Vora and Reckamp, 2008) may therefore, together with a presumed inefficiency of systemic therapy beyond the blood\u2013brain barrier (Slotman et al, 2007), constitute important prerequisites for the increased numbers of lung cancer patients" . _:b416003993 . _:b6199378 . _:b416003989 . _:b416003992 . _:b6199379 . . _:b6199388 . _:b416003995 . _:b416003978 . . _:b416003994 . _:b6199389 . _:b416004089 . _:b6199400 . . . _:b6199390 . _:b416004005 . _:b416004051 . _:b416004004 . _:b6199391 . . _:b416004021 . _:b416004007 . _:b6199384 . . _:b416004014 . _:b6199385 . _:b416004006 . _:b416004001 . _:b6199386 . . _:b416004092 . . _:b416004000 . _:b6199387 . _:b416004003 . _:b6199396 . _:b416004002 . _:b6199397 . _:b6199392 . . _:b416004013 . _:b6199398 . . _:b416004033 . _:b6199397 . _:b416004012 . _:b6199399 . _:b416004015 . _:b6199392 . . . _:b6199393 . _:b416004014 . _:b416004061 . . _:b6199398 . _:b416004009 . _:b6199394 . . _:b6199395 . _:b416004008 . _:b6199380 "In a study from the Netherlands, including 1700 lung or breast cancer patients with BM diagnosed from 1986 to 1998 (Schouten et al, >>2002<<), no similar increase in the incidence of BM was noted." . _:b6199378 . _:b416004011 . _:b6199404 . . _:b6199395 . _:b416004036 . _:b6199405 . _:b416004010 . _:b416004005 . _:b416003987 . _:b416004021 . . . _:b416004020 . _:b416004023 . _:b6199400 . _:b416004022 . _:b6199401 . _:b416004017 . _:b6199402 . _:b416004028 . . _:b6199403 . _:b416004016 . _:b6199379 "discussion" . _:b6199398 "This \u2018HER-2 paradigm\u2019 may also be relevant for other breast cancer patients in whom successful control of the disease outside of the CNS is achieved with adjuvant or palliative chemo- and radiotherapy (Lin and Winer, >>2007<<)." . _:b416004022 . _:b416004019 . . . _:b416004018 . . _:b416004038 . _:b416004029 . . _:b416004028 . . _:b416004031 . . . _:b416004030 . _:b416004100 . . _:b416004025 . . _:b416004024 . _:b6199401 "Patients with BM attributed to prostate cancer have not been included in previous studies of BM patients, which limits the possibilities of comparison (Schouten et al, 2002; Barnholtz-Sloan et al, >>2004<<)." . _:b416004027 . _:b416004026 . . _:b416004037 . . _:b416004036 . . . _:b416004039 . _:b416004002 . _:b6199396 "receptor-negative tumours and advanced stage at primary diagnosis (Palmieri et al, 2006; Lin and Winer, 2007), whereas the potential predictive value of HER-2 (expressed in 20\u201330% of breast tumours) is more uncertain (Palmieri et al, >>2006<<). The introduction of adjuvant anti-HER-2 antibody treatment, trastuzumab, with low presumed efficiency in the CNS, may have altered the natural history of patients with HER-2-positive breast cancer and unmasked CNS as a potential" . . _:b416004038 . . _:b416003998 . . _:b416004033 . _:b416004032 . _:b416004035 . . . _:b416004098 . _:b416004034 . _:b416003966 . _:b416004031 . _:b416004045 . _:b416004071 . . _:b416004029 . _:b416004044 . _:b416004047 . . _:b416004046 . _:b6199377 . _:b416004104 . _:b6199379 . _:b416004105 . _:b416004041 . _:b416004106 . _:b416004107 . _:b416004108 . _:b416004109 . _:b416004040 . _:b6199381 "For many cancer types, there has been a parallel improvement in prognosis (Lin and Winer, >>2007<<; Vora and Reckamp, 2008), likely in part because of the earlier detection of indolent tumours (Cancer Incidence in Sweden, 2007), but also because of the introduction of more effective treatment." . _:b416004052 . _:b416004110 . _:b416004111 . . _:b416004096 . _:b416004063 . _:b416004097 . _:b416004043 . _:b416004098 . _:b416004001 . _:b416004099 . _:b416004100 . _:b416004101 . _:b416004042 . . _:b416004102 . _:b416004103 . . . _:b416004053 . . _:b416004052 . _:b416004112 . _:b416004113 . _:b416004055 . _:b416004114 . _:b416004008 . _:b416004115 . _:b416004116 . _:b416004077 . _:b6199391 . _:b416004054 . . _:b416004049 . . _:b416004016 . . _:b416004066 . . _:b416004048 . _:b416004051 . . _:b416004050 . _:b416004061 . _:b6199394 "Characteristics repeatedly associated with an increased BM risk include young age, oestrogen receptor-negative tumours and advanced stage at primary diagnosis (Palmieri et al, >>2006<<; Lin and Winer, 2007), whereas the potential predictive value of HER-2 (expressed in 20\u201330% of breast tumours) is more uncertain (Palmieri et al, 2006)." . . _:b6199381 . _:b416004060 . _:b416004035 . . _:b416004063 . _:b416004062 . _:b416004034 . _:b6199400 "Patients with BM attributed to prostate cancer have not been included in previous studies of BM patients, which limits the possibilities of comparison (Schouten et al, >>2002<<; Barnholtz-Sloan et al, 2004)." . _:b416004057 . _:b416004056 . . _:b416004059 . . _:b416004058 . _:b416004004 . _:b416004069 . _:b416004068 . _:b416004060 . . _:b416004045 . _:b416004071 . . . _:b416004070 . . _:b416004065 . _:b416004088 . . _:b416004064 . _:b6199399 . _:b6199383 . . _:b416004067 . _:b416004066 . _:b416004047 . _:b416003968 . _:b416004077 . . _:b416004076 . _:b6199379 _:b6199400 . _:b416004079 . . _:b6199379 _:b6199401 . _:b416004049 . _:b6199379 _:b6199402 . _:b6199379 _:b6199403 . _:b6199379 _:b6199404 . _:b416004078 . _:b416004011 . _:b6199379 _:b6199405 . . _:b416003986 . _:b416004073 . . _:b6199379 _:b6199392 . _:b6199379 _:b6199393 . . _:b6199379 _:b6199394 . _:b6199379 _:b6199395 . _:b416003979 . _:b416004072 . _:b6199379 _:b6199396 . _:b6199379 _:b6199397 . _:b6199379 _:b6199398 . _:b6199379 _:b6199399 . _:b416004075 . _:b416004070 . _:b416004105 . _:b416004074 . _:b416004095 . _:b416004062 . . _:b416004085 . _:b416004084 . _:b6199391 "These changes, as well as a general improvement in the prognosis of breast cancer (Cancer Incidence in Sweden, 1999; 2007; Lin and Winer, >>2007<<), provide a basis for the substantial increase observed in breast cancer patients hospitalised with BM." . _:b416004087 . _:b416004114 . . . _:b416004086 . _:b416004025 . _:b416004081 . . . _:b416003982 . _:b416003971 . . _:b416004080 . . . _:b416003976 . _:b416003977 . _:b416004083 . _:b6199379 _:b6199384 . _:b416003978 . _:b6199379 _:b6199385 . _:b416003979 . _:b6199379 _:b6199386 . _:b6199377 _:b6199378 . _:b416003980 . _:b6199379 _:b6199387 . _:b416003981 . _:b416004082 . _:b6199379 _:b6199388 . _:b416003982 . _:b6199379 _:b6199389 . _:b416003983 . _:b6199379 _:b6199390 . _:b416003968 . _:b6199379 _:b6199391 . _:b416003969 . _:b416004093 . _:b416003970 . _:b416003971 . _:b416004053 . _:b416003972 . _:b416003973 . _:b416004092 . _:b6199379 _:b6199380 . _:b416003974 . _:b6199379 _:b6199381 . _:b416003975 . _:b6199379 _:b6199382 . . _:b416003992 . _:b6199379 _:b6199383 . _:b416003993 . _:b416004095 . _:b416003994 . . _:b416003995 . _:b6199395 "Characteristics repeatedly associated with an increased BM risk include young age, oestrogen receptor-negative tumours and advanced stage at primary diagnosis (Palmieri et al, 2006; Lin and Winer, >>2007<<), whereas the potential predictive value of HER-2 (expressed in 20\u201330% of breast tumours) is more uncertain (Palmieri et al, 2006)." . _:b416004048 . _:b416003996 . _:b416003997 . _:b416004094 . _:b416003998 . _:b416003999 . _:b416003984 . _:b416003985 . _:b416004089 . . _:b416003986 . _:b416004081 . _:b416003987 . . _:b416003988 . _:b416004109 . _:b416003989 . _:b416004088 . _:b416003990 . _:b416003991 . _:b416004008 . _:b416004009 . _:b416004091 . _:b416004010 . _:b416003960 . _:b416004011 . _:b416004012 . _:b416004013 . _:b416004090 . _:b416004014 . _:b416004015 . . _:b416004000 . _:b416004001 . _:b6199397 "anti-HER-2 antibody treatment, trastuzumab, with low presumed efficiency in the CNS, may have altered the natural history of patients with HER-2-positive breast cancer and unmasked CNS as a potential sanctuary site (Lin and Winer, >>2007<<). This \u2018HER-2 paradigm\u2019 may also be relevant for other breast cancer patients in whom successful control of the disease outside of the CNS is achieved with adjuvant or palliative chemo- and radiotherapy (Lin and Winer, 2007)." . _:b416004002 . _:b416004003 . _:b416004004 . _:b416004005 . _:b416004006 . _:b416004007 . . _:b416004024 . _:b416004025 . _:b416004026 . _:b416004027 . _:b416003961 . _:b416004028 . _:b416004029 . _:b416004030 . _:b416004031 . _:b416004016 . _:b416004017 . . _:b416004018 . _:b416004020 . _:b416004019 . _:b416004020 . . _:b416004021 . _:b416004022 . _:b416004023 . _:b416003990 . _:b416004040 . _:b416004041 . _:b416004042 . _:b416004043 . . _:b416004044 . _:b416004045 . _:b416004046 . _:b416004047 . _:b416004032 . _:b416004033 . _:b416004034 . _:b416004035 . _:b416004036 . _:b416004075 . _:b416004037 . _:b416004064 . . _:b416004038 . _:b416004039 . _:b416004056 . _:b416004057 . _:b416004058 . _:b416004059 . _:b416004060 . _:b416004061 . _:b416004062 . _:b416003970 . _:b416004063 . _:b416004048 . _:b416004049 . . _:b416004050 . _:b416004051 . . _:b416004052 . _:b416004053 . _:b416004054 . . _:b416004055 . _:b416004043 . _:b416004072 . _:b416004073 . _:b416004074 . _:b416004006 . _:b416004075 . _:b416004076 . _:b416004077 . _:b416004078 . _:b416004012 . _:b416004079 . _:b416004064 . . _:b416004065 . _:b416004066 . _:b6199389 . _:b416004067 . _:b416004068 . _:b416004069 . _:b416004070 . _:b416004071 . _:b416004088 . _:b416004089 . _:b416004090 . _:b416004091 . _:b416004092 . _:b416004093 . _:b416004073 . _:b416004041 . _:b416004094 . _:b416004095 . _:b416004042 . _:b416004080 . _:b416004101 "2"^^ . _:b416004081 . _:b416004082 . _:b416004083 . . _:b416004100 "2"^^ . _:b416004084 . _:b416004085 . _:b416004086 . _:b416004087 . _:b6199384 . _:b416004103 "2"^^ . . _:b416004102 "2"^^ . _:b416004097 "2"^^ . _:b6199386 "With time from lung cancer diagnosis, the proportion of patients developing BM increases rapidly (Mujoomdar et al, >>2007<<; Slotman et al, 2007)." . _:b416003976 . . _:b416004096 "2"^^ . . _:b416004097 . _:b416003974 . _:b416004099 "2"^^ . _:b416004090 . _:b416004098 "2"^^ . _:b6199382 . _:b416004109 "2"^^ . _:b416004108 "2"^^ . . _:b416004111 "2"^^ . . _:b416004110 "2"^^ . _:b416004105 "2"^^ . _:b6199405 . _:b416003964 . _:b416004104 "2"^^ . _:b416004032 . _:b416004107 "2"^^ . _:b416004106 "2"^^ . _:b416003975 . _:b6199399 "As the increase in primary melanoma incidence may be largely confined to early-stage tumours with very low, if any, metastatic potential (Rees, >>2008<<), the pool of prevalent patients truly at risk of metastatic disease may have increased much less." . _:b416004116 "2"^^ . _:b6199390 "A reported improvement in the short-term survival (Slotman et al, 2007; Vora and Reckamp, 2008) may therefore, together with a presumed inefficiency of systemic therapy beyond the blood\u2013brain barrier (Slotman et al, >>2007<<), constitute important prerequisites for the increased numbers of lung cancer patients admitted with BM of both sexes in our study." . _:b416004113 "2"^^ . _:b6199403 "The highest 1-year survival proportions, around 20%, were observed for patients with kidney, breast or prostate cancer, which is in line with previous reports for breast cancer (Palmieri et al, 2006; Altundag et al, >>2007<<), whereas studies for prostate cancer are scarce." . _:b416004112 "2"^^ . _:b416004101 . "10.1038%2Fsj.bjc.6605373" . . _:b416004115 "2"^^ . . _:b416004100 . . _:b416004114 "2"^^ . _:b416004103 . _:b416004102 . _:b416004097 . _:b416004096 . _:b416003969 . _:b416004099 . _:b416004098 . _:b416004109 . _:b416003960 . _:b416003961 . _:b416004108 . _:b416003965 . _:b416003962 . _:b416003963 . _:b416003993 . _:b416003964 . _:b416003965 . _:b416004111 . _:b416003966 . _:b416003967 . _:b416004104 . _:b416004110 . _:b416004105 . . _:b416004104 . _:b416004107 . _:b416004019 . _:b416004106 . . _:b416004003 . _:b6199387 . _:b416004116 . . _:b416003963 .