- 追加された行はこの色です。
- 削除された行はこの色です。
[[Act.14 “TOKYO JUNGLE”]]
-「いいえ」を選択した最後、切ないですね…(ノ_・,)泣いてしまった… -- [[ARA]] &new{2012-06-09 (土) 21:31:02};
-メカわんこにも人類にも救いがねぇw -- &new{2012-06-11 (月) 00:03:24};
--メカワンコはオオカミとして生涯を終えたんだ。あれは彼の本懐だよ。えぐっ(つωT) -- &new{2012-06-12 (火) 08:02:10};
-最終戦だけ別ゲー過ぎわろたww -- &new{2012-06-11 (月) 08:39:07};
--まさか動物サバイバルアクションでメカ犬どうしがビーム縄跳びするハメになるとはなぁ、、、その後感動するからさらに訳がわからなくなる(笑 -- &new{2012-06-12 (火) 07:57:24};
-そうか···施設で見たあの犬は··· -- [[車]] &new{2012-06-11 (月) 19:56:08};
-「最後の場所」に最後のアーカイブを置いたのは、実に良い演出だな・・・ -- &new{2012-06-11 (月) 23:53:45};
--あそこ行くたび切なくなるわw -- &new{2012-06-12 (火) 00:22:17};
--サバイバルモードはメカわんこのおかげで脈々と続いているんだなぁ。なんだかんだで最後は感動した。 -- &new{2012-06-12 (火) 21:13:39};
---動物を守るために人間に反抗したのにその後のサバイバルモードで最終的に全ての動物が北京原人に狩り尽くされるのは切ないな… -- &new{2012-06-17 (日) 02:00:23};
-なんか14話クリアしたあとポメラニアンでサバイバル50年以上経過で終わったら「ストーリーが追加されました」の文字が、ゲーム止めてやり直しても出現、しかし見ると14話で終わってる、まぎらわしいわw -- &new{2012-06-12 (火) 06:13:46};
--アーカイブ全部読むとそのバグ直るぞ -- &new{2012-06-15 (金) 19:04:10};
-エンディングはなんか物足りないな~ 鹿がどうなったか気になる 14話はいといいえの両方みてないと新しいストーリーが追加されましたってバグあるみたいですね -- &new{2012-06-13 (水) 05:51:42};
-エンディングはなんか物足りないな~ 鹿がどうなったか気になる 14話はいといいえの両方みてないと新しいストーリーが追加されましたってバグあるみたいですね -- &new{2012-06-13 (水) 05:51:43};
--最後に生涯を終えたメカわんこの側にやってきた二匹の鹿は、妹鹿が無事に母鹿と再開できたってことだったんじゃないかな。ヒヨコとニワトリが一緒、つまり親子ってことを表してる…と予想 -- &new{2012-06-16 (土) 09:51:42};
-サバイバルで最後の場所にいくと必ずオオカミがいるよね、良い演出だわ -- &new{2012-06-14 (木) 03:01:14};
--あの狼はERC-003の父親か母親だと思って手出ししてないわ。 -- &new{2012-06-21 (木) 20:37:12};
-まだクリアしてないけど公園に狼いるのか 恐竜と虎&牙しか出てこない -- &new{2012-06-15 (金) 22:43:59};
-実に最後の部分がよかった。 -- &new{2012-06-16 (土) 18:55:28};
-ストーリーの最後がクリアできん・・・・ -- [[けもりん]] &new{2012-06-16 (土) 23:04:30};
--ここ何回もやりなおしたw -- &new{2012-06-16 (土) 23:47:23};
-ネコの死体?がいぬの奥にあったと思うんだが、あれはなんだ? -- [[アイドルG]] &new{2012-06-16 (土) 23:49:53};
-14話のアーカイブを取得するまでのちか施設に壁があって通れません。二つはとれましたが、残りの一つはどうやって行くのですか?教えてくださぃ。 -- [[質問アーカイブ]] &new{2012-06-18 (月) 16:37:15};
--公園地下→研究施設だぞ -- &new{2012-06-19 (火) 19:19:38};
-サバイバルモードをやり込まないとアーカイブ集まらないし、やり込むからこそTOKYOJUNGLEに愛着湧いて、あの最後の場面ですよ。ゲームで泣いたのは大神以来だわ。 -- &new{2012-06-19 (火) 01:22:22};
-とりあえずストーリーモードのラストまでやってみたけど、つまらなくもなかったし、面白くもなかった。 人間は早く全滅したほうがいいよねって話でOKなのかな? それならまあ、わからないでもない。 ただ全体的に、もったいないなぁ・・・と思った。 もっと面白く出来そうなのに・・ -- &new{2012-06-20 (水) 02:10:06};
--どんなふうに -- &new{2012-06-21 (木) 09:47:26};
--人間は早く絶滅はちょっと違う気がするな。単にトーキョージャングルって設定にする為の設定で深い意味はない気がする。 -- &new{2012-06-22 (金) 00:03:33};
--ストーリーエンディングの -- &new{2012-07-08 (日) 16:49:02};
---失礼、エンディングの -- &new{2012-07-08 (日) 16:49:42};
-ラストシーンの場所の真上、地上にあるのは、忠犬ハチ公像 -- &new{2012-06-21 (木) 00:38:56};
-なぬ?そうなんか? -- &new{2012-06-21 (木) 17:39:33};
-という夢を見ました -- &new{2012-06-21 (木) 20:39:28};
-山手線の子ライオンに親よばれてやられました -- [[ポメラニアン]] &new{2012-06-21 (木) 20:56:00};
-アーカイブ最初のほうのペットの凶暴化って結局なんだったんだろう -- &new{2012-06-24 (日) 02:09:29};
--電磁波で頭がおかしくなったんじゃないか? -- &new{2012-06-26 (火) 00:32:47};
-たしかにね -- [[to-kyo-jannguru]] &new{2012-06-24 (日) 10:43:46};
-サバイバル
の研究所最後苔むした、
ビーグルかと思ってたけど、そう言う事か笑 -- &new{2012-06-27 (水) 15:45:35};
-ボス戦で負けてリトライすると、使わずに所持していた回復アイテムまで全部消えるのは仕様?バグ? -- &new{2012-06-28 (木) 01:01:15};
--仕様.状態を保存してるわけじゃなく,設定されたリスタート地点に変わるだけなんだから当たり前. -- &new{2012-06-28 (木) 20:48:18};
-アーカイブの回収自体ダルい…… -- &new{2012-07-03 (火) 18:50:10};
-動画見たおかげで一発クリア!!! -- &new{2012-07-07 (土) 14:08:37};
- 最後に逃げるところで失敗するとラスボス前からやり直しなのか…キツいわ -- &new{2012-07-07 (土) 18:46:37};
-一週目かなり死んだが、二週目一回も死なず行けてしまったww -- &new{2012-07-07 (土) 19:25:11};
-リトライしたのは初っ端のとこだけ 変に当てられるの嫌ってヒット&アウェイでいこうとしたのが失敗のもとだった -- &new{2012-07-08 (日) 03:04:13};
-アーカイブ集めるの疲れた…ブタでやるもんじゃない(笑) -- &new{2012-07-08 (日) 13:37:53};
-ストーリーの14TOKYOJYANGURUっていいえを選択したらだめですか? -- &new{2012-07-14 (土) 19:36:49};
-最後のアーカイブ取るとき瀕死の状態で突っ走って死んだからストーリーと似ててワロタ -- &new{2012-07-14 (土) 20:39:14};
-ジェット体当たりだけでなくビーム攻撃も直前にR1攻撃するとキャンセルされるような。 -- &new{2012-07-16 (月) 00:29:03};
-ローリングバスターライフル使ってきて吹いたwwwww 知ってる人いるかな? -- &new{2012-07-21 (土) 15:33:21};
-いいえにしてエンディングをみないとロボ犬手に入らないのですか? -- &new{2012-07-22 (日) 11:51:19};
-一回目でいけた -- &new{2012-07-22 (日) 15:03:22};
-W0ワロタwww -- &new{2012-07-22 (日) 16:45:14};
-切ない -- &new{2012-07-24 (火) 18:47:13};
-イイエだと手に入らないわ -- [[キルバーン]] &new{2012-07-24 (火) 23:56:29};
-アーカイブ取りに行った時、一番奥の日が差しこんでるエリアに狼が一匹寝てたんだがアイツは・・・ -- &new{2012-07-30 (月) 17:21:34};
-目頭が熱い… -- &new{2012-08-11 (土) 19:05:58};
-なんかセツナイ -- &new{2012-08-12 (日) 22:51:38};
-いいえ=死 はい=ロボ犬入手不可能 -- [[ワロスワロスわらびもち]] &new{2012-08-15 (水) 21:48:44};
-いいえ=死 はい=ロボ犬入手不可能 -- [[ワロスワロスわらびもち]] &new{2012-08-15 (水) 21:48:45};
--イイエはラスボス無視して突っ走れ!!!! -- &new{2012-11-05 (月) 18:36:06};
-まじで! -- &new{2012-08-23 (木) 16:30:21};
-ラスボスゲットできないの? -- [[神]] &new{2012-08-23 (木) 16:32:57};
--jungle無双になるじゃないか -- &new{2012-08-25 (土) 20:52:28};
--マジ泣けるわー -- [[うんこ]] &new{2013-03-18 (月) 21:26:01};
-むずい -- [[結果]] &new{2012-09-19 (水) 15:01:55};
-最後のシーンで気付いたら涙が… -- &new{2012-09-23 (日) 20:37:40};
-最後ほんと泣くね -- &new{2012-10-22 (月) 06:38:30};
-ラスボスは恐竜出てきたとこに登れば楽勝 知ってた? -- &new{2012-10-27 (土) 22:44:55};
-(ー_ー)!! 書いてたね -- &new{2012-10-27 (土) 22:50:10};
-難しいー(泣) -- &new{2012-11-17 (土) 02:23:16};
-え?エンディングどんなの??クリアむずい…… -- &new{2012-11-18 (日) 01:24:39};
-死んだ -- [[きさだ]] &new{2012-12-31 (月) 12:38:16};
-いい話だけど人類的にはBAD ENDだよなこれw -- &new{2013-01-12 (土) 15:19:31};
-www 最後はかなしぃ -- &new{2013-01-19 (土) 23:26:13};
-な、なける -- &new{2013-01-26 (土) 12:25:51};
-イイハナシダナー でも最後あのまま力尽きるなら脱出する意味がn(ry -- &new{2013-02-16 (土) 00:32:09};
--オオカミとして生きたんだろ -- &new{2013-03-10 (日) 05:55:26};
-に、逃げながら体力減ってっちゃったんだよう -- &new{2013-02-19 (火) 12:05:55};
-う~……必ずあのラスボスで行き詰まってましたー… でも、クリアしてあのERC-なんとかが壊れて草食動物が集まってくるところ感動しました~ -- [[雲雷]] &new{2013-03-03 (日) 13:47:49};
-最後の逃げる所で死んだ! -- &new{2013-04-09 (火) 18:44:47};
-サバイバルモードだと最後力尽きた所にオオカミがいるのがまた泣ける -- &new{2013-04-13 (土) 05:52:49};
-今更クリア。ラスボス慣れると楽。倒すと何故か制限時間減らされるし脱出の方が難しいw -- &new{2013-08-20 (火) 02:53:19};
-むずっ -- &new{2013-08-21 (水) 21:25:01};
-初めまして。攻略本を手に入れる前に活用するために来ました。が、どうやらここのコメント部分に、誤りがあります。今後のためにも、訂正入れさせていただきます。最初のコメントですかね、ラスボス楽勝で勝てると書かれてますが、恐竜のでてきた所に行っても、制限時間が切れるだけで、絶対勝てませんよ。おまけに、ここで紹介されてる物のことですが、飛び込み(?)したり、攻撃うけるとなかなか動かないため、大きな隙ができて攻撃されまくりになるので、ここで紹介されてる方法も、あまりおすすめとは言えません。そもそもラスボス前の2戦が時間かかる上、絶対1発で倒すことができないため、普通にやったらクリアは不可能です。秘技コードも使わない限りは・・・ネットという性質上、情報は正しく伝えて下さい。どうしても自分達の言い分が正しいというのでしたら、証拠の動画でも載せて下さい。まぁ、秘技コードを使えば、確かに楽勝でしょうけど・・・ましてや、慣れたら楽なんて事はないでしょう・・・今更なはなしですが、コメントさせていただきました。 -- [[今更男]] &new{2013-09-27 (金) 21:33:36};
-そうそう、ビームの回避方法ですが、まずジャンプなんてしてる間もなければ、遠くへ逃げてる余裕なんてありませんよ。そもそも、間に合わなかったらもうその時点で、逃げようとしたって無駄ですよ・・・ -- [[今更男]] &new{2013-09-27 (金) 21:39:02};
-ブームが終わったゲームにマジレス乙wwwwww -- &new{2013-10-04 (金) 16:46:38};
--お前もマジレス乙 -- &new{2014-02-28 (金) 09:10:04};
-攻略本を手に入れる前に活用するために来ました←国語力ゼロ -- &new{2013-10-04 (金) 16:51:23};
-さすがに下手すぎ -- &new{2013-10-07 (月) 18:15:28};
-クリアしたのにデータ消えた(泣) -- &new{2013-10-31 (木) 15:45:47};
-ここまで来られたのにラスボス勝てないの?釣られたら負けってゲームなの? -- &new{2013-11-05 (火) 01:12:26};
-ラスボス普通に勝てたけど…。サバイバルでオオカミあたりで80年くらい生き残れる実力を持ってるなら初プレイでも勝てると思います(関係ないかな?)。私は普通にやって楽勝でしたよーん。 -- &new{2013-11-16 (土) 02:25:47};
-ラスボスはコードなんて使わなくたって楽に勝てるぞwww -- &new{2013-12-01 (日) 15:57:53};
-どいつもこいつも後ろから攻撃したらちょー楽に倒せるぜオーやり方は敵が攻撃する瞬間に後ろに回る敵は1.2回攻撃してくるからそこを狙えでもラスボスには気お付けるように慣れればもうこっちの物 -- [[GGG]] &new{2014-02-15 (土) 23:03:53};
-らすぼ -- &new{2014-02-20 (木) 02:49:19};
-ラスボスは初見でも倒せますよアイテムを駆使しつつラスボスだけ狙っていけば、ザコ敵も回避からの噛みつきとラスボスの攻撃でいつの間にか打ち止めになりましたし、ビームからの光弾は少しキツいですが問題ないと思います。 -- &new{2014-02-20 (木) 02:57:43};
-18日に買ったけど次の日にはラスボス倒したな ビームもジャンプで回避できるし回復薬なんつ余るほど落ちてる -- &new{2014-03-23 (日) 14:19:55};
-回復薬なんて ですね^_^; 土佐犬で戦うサーベルタイガーの方がよっぽど苦戦しました -- &new{2014-03-23 (日) 14:30:12};
-秘技コードなんて恥ずかしい事言ってる時点でお察し -- &new{2014-04-07 (月) 13:51:50};
-まぁ、あんなの一回でクリアできるっしょ、できないやつ引くわー^_^ -- [[歯ブラシマン]] &new{2014-04-21 (月) 17:19:15};
-おいお前ら俺が弱いと言いたいのか!!!!とくにハブラシマン!!!俺にもう一度挑んでみろ!!! -- [[ラスボス]] &new{2014-05-06 (火) 17:07:45};
-あのビーム近距離でダメージデカくなるのな、舐めプしてたら3ケタくらい喰らって焦ったわ -- &new{2014-06-08 (日) 18:28:25};
-ラストステージに相応しい難易度ですね!ラスボス開始まで6分以上は欲しいです。回復大は惜しみなく使ってもいいと思いますよ。 -- &new{2014-06-10 (火) 20:23:03};
-兄が最後ボス、あの後ろからついてきたおともの子で終わりだと思っててびっくりした -- [[魔理沙LOVE]] &new{2014-08-17 (日) 08:50:32};
-鹿の3代目で40年ほどしか生きることの出来ない人でも初見で勝てる -- [[Soumu0101]] &new{2014-08-25 (月) 17:28:47};
-初見でも勝てないし攻略法とか見ても勝てないしで涙目 -- [[すぅい]] &new{2014-12-27 (土) 18:32:40};
-道中の雑魚は相手にしないでアイテムだけを取ってラスボスの前に集まったのを一層したほうが時間がかなり残ります。
&br;ディノニクスとサーベルタイガーは回避して噛みつきで削ればあっさり倒せます。
&br;ラスボスは最初は雑魚の噛みつきを回避しながらボスを攻撃してボスの体力が半分くらいなるとレーザーがきますので気をつけて下さい。
&br;レーザー回避したら2、3発攻撃離れるてレーザー回避しての繰り返しでコツコツダメージを与えると倒せます。
&br;ボスに攻撃に夢中になって雑魚の噛みつきを食らわないで下さい。 -- &color(gray){ミニチュアドーベル}; &new{2015-06-17 (水) 14:44:36};
-装置起動したら出てくる雑魚は倒して進めるようになったら後はラスボスの手間でまとめて倒して下さい。
&br;ラスボスは体力半分になると
&br;光弾、突進往復の後にレーザーきますので回避して下さい。
&br;疲れて止まった後レーザーくる時があるので離れながら回避して下さい。
&br;体力が0にならなければ回復使えるのですぐ使って立て直して下さい。 -- &new{2015-06-17 (水) 15:53:20};
-Varje dag, vecka, månad träffar våra vassa reportrar tunga personer inom näringslivet, intervjuar dem och sammanfattar höjdpunkterna i artiklar. Genom Neuraths toppmöte får läsarna och tittarna vara med och resultatet är riktigt bra tv.Neurodevelopmental Disease Models and Synapse Biology -- &color(gray){Retro 72-10 11s For Sale}; &new{2015-11-06 (金) 05:55:06};
-O art. 179 assim reza: " A Uni, os Estados, o Distrito Federal e os Municios dispensar microempresas e empresas de pequeno porte, assim definidas em lei, tratamento jurico diferenciado, visando a incentiv?las pela simplificao de suas obrigaes administrativas, tributias, previdenciias e creditias, ou pela eliminao ou reduo destas por meio de lei."Comentio:A lei fixa os pressupostos qualitativos para o enquadramento da empresa como microempresa. Tupinamb?Miguel Castro do Nascimento alerta que ser microempresa ?um direito facultado ueles que se encontrarem dentro do modelo da lei. Sem a manifestao do interessado, n h?o enquadramento. A lei n obriga a categorizao. Tudo funciona como um benefio que se propic a algu ou a uma empresa, desde que se manifestem favoravelmente, pedindo o registro especial como microempresa. Deste modo, satisfazer o critio qualitativo ?insuficiente. Tal critio ?fundamental no sentido de, inexistindo, impedir se categorizar como microempresa. Tem for de excludcia. O pedido de registro, assim, tem a natureza jurica de eficaciedade dos benefios, sendo deles fator constitutivo. 44. disp que" O registro declarar?a denominao, os fins, a sede, o tempo de durao e o fundo social, quando houver;o nome e a individualizao dos fundadores ou instituidores, e dos diretores;o modo por que se administra e representa, ativa e passivamente, judicial e extrajudicialmente;se o ato constitutivo ?reformel o tocante ?administrao, e de que modo;se os membros respondem, ou n, subsidiariamente, pelas obrigaes sociais;as condies de extino da pessoa jurica e o destino do seu patrimio, nesse caso."O artigo 47, diz: "Obrigam a pessoa jurica os atos dos seus administradores, exercidos nos limites de seus poderes definidos no ato constitutivo."E quanto deciss a serem tomadas pela pessoa jurica, como se dar?O Art. E em casos de abuso de personalidade jurica?No caso de abuso da personalidade jurica, caracterizado pelo desvio de finalidade, ou pela confus patrimonial, pode o ju decidir, a requerimento da parte, ou do Ministio Plico quando lhe couber intervir no processo, que os efeitos de certas e determinadas relaes de obrigaes sejam estendidos aos bens particulares dos administradores ou sios da pessoa jurica. (De acordo com o art. E em caso de dissoluo da pessoa jurica? Nesse caso, o art. 51 ?que responde. Leia se. "Nos casos de dissoluo da pessoa jurica ou cassada a autorizao para seu funcionamento, ela subsistir?para os fins de liquidao, at?que esta se conclua." 6. O Cigo Civil de 2002 aboliu a "sociedade de capital e indtria" como um tipo de sociedade empresia. Nestas sociedades cada sio conhece e escolhe seus companheiros. Ningu nelas ingressa ou delas se retira sem concordcia dos demais, importando o ingresso ou a retirada em modificao do contrato social. O mais importante neste tipo de sociedade ?o capital do sio acionista e n a sua pessoa. Por isso, nenhuma alterao ser?feita no contrato social em raz do ingresso ou retirada deste ou daquele sio. Desta maneira, o sio acionista ingressa na sociedade ou dela se retira, sem dar ateno aos demais, pela simples aquisio ou venda de suas aes. Ex.: sociedade anima, sociedade em comandita por aes. Frer, in "Resumo de Direito Comercial"."Neste tipo de sociedade todos os sios respondem ilimitadamente com os seus bens particulares pelas didas sociais. Se a sociedade n saldar seus compromissos, os sios poder ser chamados a faz?lo. O nome s?pode ter a forma de firma ou raz social.?a primeira modalidade de sociedade conhecida, e costuma ser chamada tamb de sociedade geral, sociedade solidia ilimitada. Frer, in "Resumo de Direito Comercial","Nesta sociedade existem dois tipos de sios. Se, por distrao, o nome de um sio comanditio figurar na raz social, este se tornar? para todos os efeitos, um sio comanditado. Referem os autores que a sociedade em comandita teve origem na comanda marima, em que o proprietio de um navio se lanva em negios al mares, aplicando capital de outrem."Em stese, na sociedade em comandita simples, a figura do comerciante aparece nos sios comanditados. S eles que: praticam os atos de comcio; gerenciam a sociedade; t seus nomes compondo a firma ou raz social; respondem ilimitadamente pelas obrigaes da sociedade.9. subscrio de todo o capital social, por duas pessoas, no mimo;2. realizao como entrada de pelo menos 10% do pre de emiss das aes subscritas em dinheiro;3. 3?e seus parrafos, da Lei n?6.404/76, "a sociedade ser?designada por denominao acompanhada da express "companhia" ou "sociedade anima", expressa por extenso ou abreviadamente, mas vedada a utilizao da primeira ao final. O nome do fundador, acionista, ou pessoa que, por qualquer outro modo, tenha concorrido para o ito da empresa, poder?figurar na denominao."Exemplos: Cia. Existe uma barreira separando as duas coisas, chamada "autonomia patrimonial" da pessoa jurica. Salomon era sio de uma empresa com mais outros tantos sios, a Salomon Company, que tornou se insolvente. Os credores questionaram o disfarce da Salomon Company, alegando que esta era uma extens da personalidade do Sr. Salomon, pois este, atrav da companhia, fraudava mais facilmente, praticando atos que n poderia praticar enquanto pessoa natural. O juiz de primeira instcia deu ganho de causa aos credores e disse que o Sr. Salomon de fato era sinimo da Salomon Company. Mesmo com a reforma da senten em instcia superior, com o tribunal dizendo que o Sr.Sodium Chloride Injection 23 -- &color(gray){toms shoes}; &new{2015-11-07 (土) 08:31:51};
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-AbstractObjective To examine whether high milk consumption is associated with mortality and fractures in women and men.Participants Two large Swedish cohorts, one with 61433 women (39 74 years at baseline 1987 90) and one with 45339 men (45 79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.Results During a mean follow up of 20.1 years, 15541 women died and 17252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow up of 11.2 years, 10112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8 iso PGF2 (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.IntroductionA diet rich in milk products is promoted to reduce the likelihood of osteoporotic fractures. Milk contains 18 of 22 essential nutrients, including calcium, phosphorus, and vitamin D of especial importance for the skeleton. Intestinal uptake of these nutrients is enhanced by the enzymatic capacity to digest lactose into D glucose and D galactose by mutation in the lactase gene, a variant common in those with northern European ancestry.1 2 An intake of dairy foods corresponding to three or four glasses of milk a day has been suggested to save at least 20% of healthcare costs related to osteoporosis.3A high intake of milk might, however, have undesirable effects, because milk is the main dietary source of D galactose. Experimental evidence in several animal species indicates that chronic exposure to D galactose is deleterious to health and the addition of D galactose by injections or in the diet is an established animal model of aging.4 5 6 7 Even a low dose of D galactose induces changes that resemble natural aging in animals, including shortened life span caused by oxidative stress damage, chronic inflammation, neurodegeneration, decreased immune response, and gene transcriptional changes.5 7 A subcutaneous dose of 100 mg/kg D galactose accelerates senescence in mice.5 This is equivalent to 6 10 g in humans, corresponding to 1 2 glasses of milk. Based on a concentration of lactose in cow's milk of approximately 5%, one glass of milk comprises about 5 g of D galactose. The increase of oxidative stress with aging and chronic low grade inflammation is not only a pathogenetic mechanism of cardiovascular disease and cancer in humans8 9 but also a mechanism of age related bone loss and sarcopenia.9 10 The high amount of lactose and therefore D galactose in milk with theoretical influences on processes such as oxidative stress and inflammation makes the recommendations to increase milk intake for prevention of fractures a conceivable contradiction.Because of the high content of lactose in milk, we hypothesised that high consumption of milk may increase oxidative stress, which in turn affects the risk of mortality and fracture. Meta analyses of cohort studies for the association between dairy and milk intake in relation to mortality11 and fractures12 13 have displayed no clear pattern of risk, and evidence from randomised trials are lacking. Separating milk intake from the consumption of other dairy products may be of importance since a less pronounced induction of oxidative stress and inflammation in humans is expected with cheese and fermented dairy products (for example, soured milk and yogurt) because of their lower or non existent lactose and galactose content,14 15 possible probiotic antioxidant and anti inflammatory effects,16 17 18 and effects on gut microbiota.19 20 21 Indeed, a high intake of fermented milk products has been associated with a decreased risk of cardiovascular diseases,18 22 23 24 whereas a high milk intake is related to a tendency of an unfavourable risk profile for the development of diabetes and cardiovascular disease.18 23 24 We therefore assessed the relation between high milk intake with risk of death and fractures in women and men. We also studied biological markers of oxidative stress and inflammation in relation to milk intake in humans.MethodsWe used two community based cohorts, the Swedish Mammography Cohort25 26 and the Cohort of Swedish Men,27 to analyse the association of milk consumption and mortality and fracture rates. Figure 1 shows the study sample. In 1987 90, all 90303 women aged 39 74 years residing in two Swedish counties (Uppsala and Västmanland, both in central Sweden) received a postal invitation to a routine mammography screening. Enclosed with this invitation was a questionnaire covering both diet (food frequency questionnaire) and lifestyle, which was completed by 74% of the women. In 1997, a subsequent, expanded questionnaire was sent to those who were still living in the study area (response rate 70%). In the present study 61433 women in the Swedish Mammography Cohort with baseline data from 1987 90 and 38984 with updated information from 1997 were available for analysis.The Cohort of Swedish Men was created in the autumn of 1997. All men, aged 45 79 years, residing in Örebro and Västmanland counties in central Sweden were invited to participate in the study (n=100303). Enclosed with this invitation was a questionnaire covering both diet (food frequency questionnaire) and lifestyle, which was completed by 48850 men. Despite the response rate of 49%, the Cohort of Swedish Men is considered representative of Swedish men in this age range in terms of age distribution, educational level, and prevalence of being overweight.27 After exclusions, the final sample included 45339 men (fig 1).Flow chart of study samplesFig 1 Flow chart of study samplesOpen in new tabFood frequency questionnairesThe participants reported their average frequency of consumption of up to 96 foods and beverages during the past year,25 27 28 that is, how many servings, a day or a week, they consumed of common foods, including milk, fermented milk, yogurt, and cheese. Instructions were given that one serving of milk corresponded to one glass of 200 mL. In the first questionnaire in the Swedish Mammography Cohort the categories were prespecified, but in the second questionnaire and the one used in the Cohort of Swedish Men, participants could fill in the exact number of servings of the dairy products (milk, fermented milk, yogurt, and cheese) they consumed a day or a week. Milk intake was specified according to fat content, and we summed intake into a single measure representing total milk intake on a continuous scale. We estimated nutrient intakes by multiplying the consumption frequency of each food item by the nutrient content of age specific portion sizes and reference data obtained from the Swedish National Food Agency database.29 The residual method was used to adjust all nutrient intakes for total energy intake.30 According to validation studies of milk intake, the correlation between the food frequency questionnaire and four, seven day food records every third month, a gold standard reference, has been approximately 0.7.31 Furthermore, in both sexes we have found a positive association between reported intake of milk and the fat tissue content of pentadecanoic acid, a biological marker reflecting average long term intake of milk fat that is, present in both milk and fermented milk products.32 33OutcomesWe considered outcomes registered between study entry (date of mammography screening in 1987 90 for the Swedish Mammography Cohort and 1 January 1998 for the Cohort of Swedish Men) and 31 December 2010. Follow up until death was through the Swedish cause of death registry. Complete linkage with the register is possible by the personal identity number provided to all Swedish residents. We used the underlying cause of death from the Swedish cause of death registry to define mortality from all causes, cardiovascular diseases (international classification of diseases, 10th revision; ICD 10 codes I00 I99), and cancer (ICD 10 C codes). For 1987 to 1996, we used corresponding ICD 9 codes. Accuracy of classification of causes of death in the Swedish registry is high.34We collated fracture events through linkage with the Swedish national patient registry. We defined any fracture event as a hospital admission or an outpatient visit with ICD 10 codes S12 S92. Hip fracture cases were defined by the codes S720 S722. Using a previously validated and accurate method, we separated admissions for incident fracture from readmissions for a previous fracture event.25 35 In analyses we used only the first fracture event. We retained cases of fractures due to suspected high impact trauma in the analysis since there are indications of comparable increases in the risks of low impact and high impact trauma fractures in association with decreasing bone density in elderly people (60 years).36 37 Pathologic fractures as a consequence of a tumour were not included as an outcome.Comorbidity and other additional informationFrom the questionnaires we obtained information on lifestyle, weight, and height. For the Swedish Mammography Cohort the questionnaires also covered information on use of postmenopausal oestrogen therapy, menopausal status, and parity. In the 1997 questionnaires for both cohorts, information was collected on smoking status, ever use of cortisone, and leisure time physical activity during the past year, with five predefined categories ranging from one hour a week to more than five hours a week. This physical activity assessment is valid compared with activity records and accelerometer data.38 We divided educational level into four categories: 12 years, and other (such as vocational). Living alone was categorised based on marital status (yes: unmarried, divorced, widow/widower; no: married, cohabiting). To calculate Charlson's comorbidity index we collated diagnosis codes from the national patient registry.39 40BiomarkersD galactose supplementation in animals has been shown to increase oxidative stress and inflammation.4 5 6 7 To assess the association between milk intake and biological markers of oxidative stress and inflammation (fig 1), we additionally analysed a clinical subcohort of the Swedish Mammography Cohort25 and the previously described Uppsala Longitudinal Study of Adult Men cohort.41 We assessed food intake by a third food frequency questionnaire in the Swedish Mammography Cohort Clinical (n=5022; mean age 70 years) and by recording diet for one week at age 71 years in the Uppsala Longitudinal Study of Adult Men (n=1138). In 892 women (mean age 70 years) and 633 men (urine collected at age 77) we analysed the urine oxidative stress marker 8 iso PGF2, a dominant F2 isoprostane and an ideal standard biomarker of oxidative stress in vivo.42 We used serum from the same age group in the Uppsala Longitudinal Study of Adult Men to analyse interleukin 6 (a main inflammatory biomarker, n=700).Statistical analysisFor each participant we calculated time at risk until date of each outcome, date of emigration, or the end of the study period (31 December 2010), whichever occurred first. We used Cox proportional hazards regression for estimation of age adjusted and multivariable adjusted hazard ratios and their 95% confidence intervals for prespecified categories of milk intake (18 23 we additionally studied intake of fermented milk and cheese as exposures. The proportional hazard assumptions were confirmed graphically by log log plots. We assessed non linear trends of risk using restricted cubic spline Cox regression with three knots placed at centiles 10, 50, and 90 of the milk product intake.43We used the directed acyclic graph approach44 to select suitable covariates for the multivariable model (see supplementary appendix figure A). The model included age, total energy intake, body mass index, height (all continuous), educational level (9, 10 12, >12 years, other), living alone (yes/no), calcium supplementation (yes/no), vitamin D supplementation (yes/no), ever use of cortisone (yes/no), a healthy dietary pattern, as previously described45 (continuous), physical activity (five categories), smoking status (never, former, current), and the Charlson comorbidity index (continuous, 1 16). We included other potential covariates such as menopausal status; hormone replacement therapy; intakes of calcium, vitamin D, total fat, saturated fat, retinol, alcohol, potassium, phosphorus, and protein; parity; and previous fracture of any type (the last when analysing hip fracture as an outcome, in a second multivariable model to assess whether these covariates confounded or mediated potential associations). In the Swedish Mammography Cohort, of which we had access to information from repeat questionnaires, we time updated exposures and covariates, theoretically yielding stronger outcome associations.46 The analysis in the Cohort of Swedish Men was based on a single exposure assessment. Using the Markov chain Monte Carlo multiple imputation methods, we imputed covariates not assessed in the baseline questionnaire of the Swedish Mammography Cohort in 1987 90 but assessed in the second questionnaire in 1997 (for example, smoking status and physical activity). We performed sensitivity analysis limiting the analysis to baseline data at 1987 90 and 1997 using ordinary Cox's regression without time updated information. In an additional sensitivity analysis, we adjusted our estimates for milk intake by fermented milk and cheese intakes, and vice versa. We also adjusted our second multivariable model for additional nutrients (except lactose) known to be constituents of milk. Accordingly, we therefore evaluated the change of our hazard ratios after adjustment for intakes of riboflavin, thiamine, niacin, vitamin B6, vitamin B12, folate, carotene, iron, magnesium, sodium, selenium, and zinc.To assess the influence of competing events, we compared cumulative incidence curves for hip fracture, treating death from all causes as competing event, with the Kaplan Meier curves for hip fracture by categories of milk intake.47 Even though competing risk analysis is not considered appropriate for causal analysis, which was the purpose of our study, it can provide additional valuable information for risk prediction.48 We undertook a further sensitivity analysis with any type of vehicle related non fracture incident as an outcome (identified by ICD 10 codes V01 99 excluding simultaneous fracture), which should theoretically be unrelated to consumption of milk. We evaluated whether a history of fracture was associated with milk consumption in the Uppsala Longitudinal Study of Adult Men cohort and whether experiencing a fracture or comorbidity between the first and second food frequency questionnaires was associated with changed milk consumption in the Swedish Mammography Cohort.Finally, we used cubic spline regression analysis to assess the relation between intake of milk, fermented milk, or yogurt, cheese, the urine oxidative stress marker 8 iso PGF2, and serum interleukin 6. Before analysis we log transformed both biomarkers because of their skewed distributions. We adjusted the estimates for age, body mass index, energy intake, education (four categories), smoking status (never, former, current), and physical activity (four categories). The statistical analyses were performed with STATA 11.2 (StataCorp, College Station, TX) and SAS, version 9.3 (SAS Institute, Cary, NC).ResultsTable 1 lists the characteristics of the study participants by categories of milk intake. Mean intake of milk at baseline in the Swedish Mammography Cohort was 240 g a day and in the Cohort of Swedish Men was 290 g a day. With increasing categories of milk intake the reported intake for most other nutrients, including energy intake, also increased, although alcohol intake tended to decrease. There were generally small differences between categories of milk intake in body stature, nutritional supplement use, marital status, comorbidity, educational level, smoking status, and physical activity level.Table 1 Baseline characteristics of women in Swedish Mammography Cohort (1987 90) and men in Cohort of Swedish Men (1997) by categories of milk intake. 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