Long-term survival after an aggressive surgical resection and chemotherapy for stage IV pulmonary giant cell carcinoma

BACKGROUND: Pulmonary giant cell carcinoma is one of the rare histological subtypes with pleomorphic, sarcomatoid or sarcomatous elements. The prognosis of patients with this tumor tends to be poor, because surgery, irradiation and chemotherapy are not usually effective. CASE PRESENTATION: We herein report a patient with pulmonary giant cell carcinoma with stage IV disease in whom aggressive multi-modality therapy resulted in a long-term survival. A 51-year-old male underwent an emergent operation with a partial resection of small intestinal metastases due to bleeding from the tumor. The patient also underwent a left pneumonectomy due to hemothorax as a result of the rapid growth of the primary tumor. Thereafter, two different regimens of chemotherapy and a partial resection for other site of small intestinal metastases and a splenectomy for splenic metastases were performed. The patient is presently doing well without any evidence of recurrence for 3 years after the initial operation. CONCLUSION: This is a first report of a rare case with stage IV pulmonary giant cell carcinoma who has survived long-term after undergoing aggressive surgical treatment and chemotherapy

Toxic Substances in the Flowers pf Pieris japonica

It has been reported that several toxic diterpenoids, Pieristoxins and Asebotoxins, were isolated from the flowers of Pieris japonica D. Don (Ericaceae). The structures of Asebotoxin-I, II, III, IV, V and VII are known, but those of Pieristoxin A, B, C and D are unknown. We isolated five diterpenoids, compound-I, II, III, IV and V, from the same flowers. The structures of these compounds were investigated. From the comparison of the spectral data and the chemical facts, compound-I, mp 190-191°, and compound-II were found to be identical with Asebotoxin-I C23H38O7, mp 196-198°, and Asebotoxin-VII C25H38O10, respectively. The IR spectrum of compound-III (mp 257-260°) was identical with that of Pieristoxin-B (mp 257°). Compound-ID: was hydrolysed to give lactic acid and desacyl Pieristoxin-B (Pieristoxin-E, mp 280-282°), which showed the same IR spectrum with compound-IV (mp 260-276°). The analysis of the NMR spectrurm of Pieristoxin-E showed the presence of the same functional groups to those of Rhodojaponin-III C20H32O6 (desacyl Asebotoxin-III, mp 285-287°). The melting point of Pieristoxin-E is close to that of Rhodojaponin-III, but those of monoacetyl Pieristoxin-E (mp 280-283°) and diacetyl Pieristoxin-E (mp 236-238°) differ from those of monoacetyl Rhodojaponin-III (Rhodojaponin-II mp 294.5-296°) and diacetyl Rhodojaponin-III(Rhodojaponin-I, mp 248.5-250°), respectively. The C-14 hydrogen signal (6.18 ppm) in the NMR spectrum of Pieristoxin-B indicates that Pieristoxin-B is 14-lactoyl Pieristoxin-E. The NMR spectrum of Pieristoxin-B is similar to that of Rhodojaponin-V (14-acetyl Rhodojaponin-III except that the signals due to the O-acetyl group in the latter is replaced by the signals due to the O-lactoyl group in the former. It is likely that Pieristoxin-B and E are identical with Asebotoxin-III and Rhodojaponin-III, respectively. The structure of compound-V C25H40O9, mp 203-205°, was shown by the chemical and spectral characteristics to be 7-acetoxy-14-propionyl Grayanotoxin-III or 7-propionyloxy-14-acetyl Grayanotoxin-III

Prognostic value of visceral pleural invasion in resected non–small cell lung cancer diagnosed by using a jet stream of saline solution

AbstractObjectiveVisceral pleural invasion caused by non–small cell lung cancer is a factor in the poor prognosis of patients with that disease. We investigated the relationship between the diagnosis of visceral pleural invasion by using a jet stream of saline solution, which was previously reported as a new cytologic method to more accurately detect the presence of visceral pleural invasion, and prognosis.MethodsFrom January 1992 through December 1998, 143 consecutive patients with peripheral non–small cell lung cancer that appeared to reach the visceral pleura underwent a surgical resection at the Department of Thoracic Oncology, National Kyushu Cancer Center. The surface of the visceral pleura in patients undergoing lung cancer resection was irrigated with a jet stream of saline solution. The diagnosis of visceral pleural invasion was determined by means of either a pathologic examination or by means of a jet stream of saline solution. In addition, a cytologic examination of the pleural lavage fluid obtained immediately after a thoracotomy was evaluated.ResultsForty-nine (34%) resected tumors were identified as having visceral pleural invasion. The diagnosis of visceral pleural invasion in 31, 6, and 12 patients was determined by using a jet stream of saline solution alone, pathologic examination alone, or both, respectively. The visceral pleural invasion and positive findings of intrapleural lavage cytology were linked. Although there was no significant difference between the incidence of distant metastases in the patients with visceral pleural invasion and those without visceral pleural invasion, the incidence of local recurrence, especially regarding carcinomatous pleuritis (malignant pleural effusion, pleural dissemination, or both), in the patients with visceral pleural invasion was significantly higher than in those without visceral pleural invasion. The recurrence-free survival of patients with visceral pleural invasion was significantly shorter than that of patients without visceral pleural invasion (P = .004), even patients with stage I disease (P = .02). There was also a significant difference between the patients with or without visceral pleural invasion in the overall survival (P = .02). Visceral pleural invasion was independently associated with a poor recurrence-free survival on the basis of multivariate analyses (P = .03), as were sex (P = .03), age (P = 002), and the stage of the disease (P < .0001).ConclusionsThis study confirmed that the jet stream of saline solution method in addition to ordinary pathologic examination was useful for detecting visceral pleural invasion, which is considered to be one of the causes of local recurrence, especially in carcinomatous pleuritis

ブンプ ホクゲンイキ イリオモテジマ ノ マヤプシキ ニ オケル ホウカ ドウブツシュ ト ホウカ ジカンタイ ノ キセツ ヘンカ

マングローブ植物のマヤプシキは，夜間に開花するコウモリ媒花であり，熱帯ではオオコウモリ科の果実・花蜜食性の小型コウモリが花粉媒介者となっている。分布北限域である西表島のマングローブ林には，オオコウモリ科のコウモリはほとんど分布せず，ヤエヤマオオコウモリ1種のみが分布するが，マヤプシキへの訪花は確認されていない。そこで，分布北限域の西表島において，マヤプシキはどのような動物種により代替的に送粉されているのかを明らかにするため，マヤプシキへ訪花する動物種とその訪花頻度の日・季節変動を調べた。マヤプシキ13個体に訪花する動物を，4季節にわたり夜間を含むのべ225時間9分記録した。その結果，鳥類，膜翅目，双翅目，鱗翅目，およびカニ類が訪花動物種として観察された。観察時間内の訪花回数は764回を数えたが，ヤエヤマオオコウモリの訪花は確認されなかった。それらのうち鱗翅目のガ類のみがマヤプシキの開花時間に対応した夜間に訪花したが，送粉よりも盗蜜者的な行動を示した。ガは主に秋季に訪花した。リュウキュウメジロなどの鳥類とスズメガ科のホウジャクの一種は，葯と柱頭の両方に接触するとともに次々と花を移動したため，有効な送粉者と考えられた。しかし，花が満開の夜間には訪花せず，昼間の訪花頻度も小さかった。ニホンミツバチは4季節を通じて訪花が観察されたが，体サイズが花に対して小さく，送粉に関わりなく花粉や蜜のみを選択的に集めることが可能だった。以上のように，分布北限域の西表島では，マヤプシキに対して効率よく送粉を行う訪花者が少なく，花粉制限が存在する可能性が示唆された。Mangrove apple (Sonneratia alba) has nocturnal and chiropterophilous flowers. Abundance of flying foxes, the potential pollinator of S. alba in the tropics, is known to be negligible in mangrove forests in Iriomote Island, which is the northern range limit of S. alba. Unless alternative pollinator community without flying fox functions as an effective pollinator of the S. alba population of Iriomote Island, S. alba population may receive pollen limitation. The aim of this study is to examine the seasonal changes of pollinator species and their visiting time to S. alba in Iriomote Island. We recorded the pollinator species and their behavior on 13 S. alba trees during all day including night for four seasons (totally 229h 9 m). We found a total of 764 visitations of birds, Hymenoptera, Diptera, Lepidoptera and crabs as flower visitors, while flying fox could not be found. Moths only visited the flowers at night, when S. alba’s flowers bloom. But moths visited flowers only in autumn, and behaved like nectar robber. Birds and hawk moths touched both of anther and stigma, and then, visited flowers one after another, indicating potential as effective pollinators. However, they usually did not visit the flowers at night when they bloom, and their visitation frequency was relatively low. Honeybees visited to flowers irrespective of seasons. However, their body size is too small relative to the flower, and they can directly obtain pollens and nectar without pollination. Accordingly, because of a limited number of effective pollinators, S. alba may receive pollen limitation in their northern range limit

タマガワゲンリュウイキ ノ チュウオオガタホニュウルイソウ ショクガイヨボウ ノ タメ ノ センサーカメラ ニ ヨル ジゼンチョウサ

多摩川源流域山梨県小菅村の奥山2地域と里山2地域の計4地域において,2008年4月から12月までの9ケ月間,6台のセンサーカメラによって,げっ歯目と翼手目を除く中大型哺乳類相の調査を実施した(1,130カメラ日)。その結果,11種の中大型哺乳類が確認され,撮影頻度(100カメラ日あたりの撮影枚数)が高い種は,上位からニホンジカ(Cervus nippon ; 12.9),イノシシ(Sus scrofa ; 5.4),テン(Martes melampus ; 4.5),ニホンザル(Macaca fuscata ; 3.3),そしてタヌキ(Nyctereutes procyonoides ; 3.1)であった。1位のニホンジカの撮影頻度の割合(32.7%)は,2位のイノシシ(13.7%)に比べ2.4倍高く,4地域すべてにおいて相対的に高い値を示した。また,調査4地域において,対象種の撮影頻度の合計が最も高い傾向を示したのは,湧水域を対象とした奥山地域B(120.2 ; 8種)で,続いて里山地域A(46.0 ; 9種),里山地域B(44.5 ; 10種),奥山地域A(17.3 ; 10種)の順であった。湧水域の撮影頻度の高さは,この地域の個体数あるいは利用頻度の高さを反映したものであり,この地域が野生生物管理にとって鍵となる環境であることが示唆された。Census of the middle to large mammalian species except for rodents and Chiroptera was conducted by 6 camera-traps at 2 areas of a secluded mountain and 2 areas near villages in a total of 4 areas of Kosuge, Yamanashi, central Japan for 9 months from April to December 2008 (1,130 camera-day). The 11 species were photographed and compared with the photographed frequency (number of photographs per 100 days). The top five species were the sika deer (Cervus nippon ; 12.9), followed by the wild boar (Sus scrofa ; 5.4), the Japanese martin (Martes melampus ; 4.5), the Japanese macaque (Macaca fuscata ; 3.2), and the raccoon dog (Nyctereutes procyonoides ; 3.1). The rate of photographed frequency of the sika deer (32.7%) was 2.4 times higher than that of the wild boar (13.7%). Between 4 areas the sum of photographed frequency of focal species was the highest in the area of secluded mountain A containing spring water (120.2 ; 8 species), followed by the area near the villages A (46.0 ; 9 species), B (44.5 ; 10 species), and the area of secluded mountain B (17.3 ; 10 species). The photographed frequency at the spring water may reflect population density and/or visitation frequency of the animals, and suggests that the area is one of the important habitats for wildlife management

ブンプジョウゲン ニ オケル アカガシ ノ トウキ ノ コウゴウセイトクセイ

本研究は,暖温帯常緑広葉樹の分布上限決定機構を検討するために,暖温帯常緑広葉樹林と冷温帯落葉広葉樹林の植生帯境界域において,アカガシの冬季の光合成速度および光阻害を受ける度合いが,標高の上昇による気温の低下や光環境の変化によって,どのように変化するのかを明らかにした。分布の中心である標高600mの常緑広葉樹林,分布上限の標高1000mの落葉広葉樹林およびその中間の標高800mの3標高において,それぞれ林内と林外にポットを設置し,そこで発芽したアカガシの当年生実生を用いて測定を行った。冬季(1月)の最大光合成速度(Amax)は,全標高の林外と標高1000mの林内ではほぼ0となった。それに対し,標高600mの林内では,冬季のAmaxは秋季(10～12月)と同程度に維持されていた。結果として,林内についてみてみると,冬季のAmaxは,標高の上昇に伴い低下することになった。1月のAmaxと2月の葉内CO2-光合成曲線の結果から算出した最大炭酸同化速度(Vcmax),最大電子伝達速度(Jmax)および飽和CO2濃度時の光合成速度は,林内に比べ,林外で一様に低い値を示した。林内では,これらの値は,標高の上昇に伴い低下した。光阻害の度合いを指標する最大量子収率(Fv/Fm)は,冬季には林外と標高1000mの林内で著しく低く,冬季の光合成速度の低下は,光阻害に強く関係することが示された。ただし,標高800mの林内では,冬季にもFv/Fmは高く維持されていたことから,ここでは,冬季の気温の低下によるVcmaxやJmaxの低下が光合成速度の低下をもたらしていることが示された。以上のことから,アカガシ当年生実生の冬季の光合成の低下は,まず標高の上昇に伴う気温の低下によって,さらに分布上限では,林冠の落葉樹が冬季に落葉し,光強度が増すことによって,光阻害を受けるために,さらなる低下がもたらされていることが示唆された。Magnitude of winter depression of photosynthesis and photoinhibition were examined for current year seedlings of Quercus acuta thunb. under different light conditions (open and closed canopy) at different altitudes (600m, 800m and 1000m a.s.l.) in order to understand the determinants of upper limit of vertical distribution in warm-temperate evergreen broad-leaved trees. In winter, light saturated rate of photosynthesis (Amax) decreased to zero under the open canopy at all three altitudes and under the closed canopy at 1000m a.s.l., while Amax under the closed canopy at 600m a.s.l. was kept as that in autumn. Amax under the closed canopy decreased with increasing altitude in winter. The maximum rate of RuBP carboxylation (Vcmax), the maximum rate of electron transport (Jmax) and CO2 saturated rate of photosynthesis were significantly lower under the open canopy than under the closed canopy at all three altitudes in winter. Under the closed canopy, those values decreased with increasing altitude. The maximum photochemical efficiency (Fv/Fm) as an index of photoinhibition became less than 0.3 under the open canopy at all three altitudes and under the closed canopy at 1000m a.s.l., which indicated the effect of photoinhibition on the winter depression of photosynthetic rate. However, Fv/Fm was kept above 0.7 under the closed canopy at 800m a.s.l. in spite of the decrease in Amax in winter. It suggests that the decrease of Vcmax and Jmax due to low temperature rather than photoinhibition affects the decrease of photosynthetic rate in winter at this site. Accordingly, decrease of the photosynthetic rate at high altitude may be brought about by the decrease of Vcmax and Jmax due to decrease of temperature with increasing altitude, and further decrease of photosynthetic rate may be brought about by the photoinhibition due to the leaf fall of deciduous broad-leaved canopies at upper limit of vertical distribution in Quercus acuta

An Evaluation of Surgical Problems for Carcinoma of Esophagus in view of Autopsy Findings

By comparison of the findings in operation and those in autopsy, 9 cases of death within 30 days after esophagectomy and dissection of the lymph node for thoracic esophageal cancer were examined mainly on the influence of dissection of the lymph node. In autopsy, remained metastatic lymph node was observed in 4 of them (44,4%). Remained metastatic thoracic lymph node was to the tracheobronchial lymph node group. Metastatic abdominal lymph node was observed in many cases at the operation, but in autopsy remained cancer in this area was not observed. It is proved that remained metastatic lymph node in the abdomen at autopsy is in paraaortic lymph node in high rate. It was examined by the experiment with the dogs that frequency of pulmonary complication will be higher if extended radical mediastinal lymph node dissection is performed. In the experiment, decrease of lung surfactant, rise in pulmonary wedge pressure, trouble in perfusion of pulmonary lymph flow in the experiment by dye solution, and interstitial edema and alveolar edema in the lung in histological examination were observed. As described above, since direct operative death after esophagectomy is related to respiratory complications, treatments for this complications may be able to be improved, if the cause is made clear and pathological treatments are carried out. In order to improve surgical treatments for metastasis to the lymph node of esophageal cancer, these points should be given attention to

Vergleichende Studien des Pinus-Krummholzes in den japanischen und europäischen Alpen

Die Formation des von Nadelhölzern beherrschten Krummholzes ist sowohl in den japanischen als auch in den europäischen Alpen landschaftsprägend entwickelt; die beiden Ausbildungen werden hier vergleichend-autökologisch und vergleichend-pflanzensoziologisch betrachtet. Schlüsselart des (Nadel-) Krummholzes ist in Japan Pinus pumila (Pall.) Regel, in Europa Pinus mugo Turra. P. pumila unterscheidet sich bei an sich gleichem Wuchs durch die Fähigkeit, an älteren Ästen Nebenwurzeln und damit Polykormone zu bilden. Messungen der Nadellängen bei P. pumila zeigten: Die Nadellänge korreliert mit den Sommertemperaturen des Jahres, in dem das Streckungswachstum stattfindet, die Zahl der Nadelbüschel mit den Temperaturen des (vorhergehenden) Sommers, in dem sie angelegt wurden. Zur Bestimmung der auffallenden Biegesteifigkeit und Bruchfestigkeit der Äste wurden 2 Methoden zu deren Messung entwickelt (Abb. 2-4). Die Biegesteifigkeit ist jeweils abhängig vom Astdurchmesser und bei der baumförmigen P. cembra und bei Tieflagen-Herkünften von P. mugo geringer als bei P. pumila und Hochlagen-Herkünften von P. mugo. Ökologisch entscheidend ist die wesentlich höhere Bruchfestigkeit von P. mugo-Hochlagen-Herkünften gegenüber Tieflagen-Herkünften und P. cembra. P. mugo ist anemochor; P. pumila bildet wie ihre Elternart P. cembra geschlossen bleibende Zapfen; die Samen werden von Tieren, vor allem dem Tannenhäher, Nucifraga caryocatactes (in Asien in der ssp. macrorhynchos) ausgebreitet. Jungpflanzentrupps von 2 bis 8 Pflanzen wurden von uns im Faurio-Caricetum blepharicarpae des Naeba-Gebirges gefunden; ihr gleichmäßiges Alter von 8-9 Jahren läßt auf Verjüngung in mehrjährigen Abständen schließen. Die Einheitlichkeit des Krummholzes in beiden Gebieten wird dadurch belegt, daß es von nur je einer Assoziation gebildet wird, dem Vaccinium-Pinetum pumilae Maeda et Shimazaki 1951 bzw. dem Rhododendro-Mugetum Br.-Bl. 1939 em. Oberd. 1957. Die aktuelle Ausdehnung des Krummholzes entspricht in den Japanischen Alpen in sehr viel höherem Maße dem potentiellen Areal als in Europa, wo die Almwirtschaft direkt und indirekt zu einer Zerstückelung oder Vernichtung geführt hat. Die relativen Höhenlagen sind verschieden: die räumliche Durchdringung mit dem Nadelholz-Stammwald-Gürtel ist in Europa viel stärker; in Japan gibt es im oberen Grenzbereich bereits Frostböden. Im strukturellen Aufbau aus 3 Schichten (Pinus sp., Ericaceen, Kryptogamen) gleichen sich die beiden Assoziationen; die Artenzahlen sind jedoch im europäischen Krummholz wegen stärkerer Auflichtung höher. Das Vaccinio-Pinetum pumilae ist eine klare Vaccinio-Piceetea-Assoziation; das Rhododendro-Mugetum nimmt eine Übergangsstellung zu den Erico-Pinetea ein und wird von uns dieser Klasse zugeordnet. Hierin spiegelt sich die verschiedene Synevolution unserer Gesellschaften: Das Vaccinio-Pinetum pumilae ist aus Arten nordischer Verbreitung, vermutlich aus der arktotertiären Flora stammend, aufgebaut, lediglich seine Rhododendren könnten den Lorbeerwäldern entstammen. Das Rhododendro-Mugetum enthält dagegen zusätzlich zu den nordischen Arten wesentliche alpigene Arten. Das Vaccinio-Pinetum pumilae wird oft von "Zwergmänteln" umrandet, je nach Windexponiertheit dem Arctoo alpini-Vaccinietum uliginosi oder dem Arcterio nanae-Loiseleurietum procumbentis angehörend. In den europäischen nördlichen Kalkalpen bilden Rhododendron hirsutum bzw. ferrugineum ebenfalls Randstreifen, die sich aufnahmetechnisch und syntaxonomisch allerdings schwer aus dem Krummholz selbst herauslösen lassen. Eine "relative Ökologie" läßt sich aus den Kontaktgesellschaften ablesen (Abb. 5): Eine "mittlere" Schneebedeckung, die schätzungsweise mindestens 4 Monate Vegetationszeit erlaubt, aber auch einen gewissen Schutz gegen Frosttrocknis bietet, benötigen beide Gesellschaften. Verschieden sind die edaphischen Ansprüche: das Vaccinio-Pinetum pumilae ist eine Silikatgesteins-Gesellschaft, das Rhododendro-Mugetum stockt auf Kalkgestein, freilich oft mit autogener saurer Streudecke. Rasengesellschaften und Rasenarten kommen in den Japanischen Alpen in weit geringerer Vielfalt vor; die Gründe hierfür werden diskutiert.Conifer-dominated krummholz is characteristic of both the Japanese and the European Alps. This paper compares the autecology and plant sociology of the two formations. The key species of the coniferous krummholz is Pinus pumila (Pall.) Regel in Japan and Pinus mugo Turra in Europe. The difference between the two is the ability of P. pumila to form adventitious roots and hence polycorms. Measurements of P. pumila revealed that needle-length correlates with the summer temperature of the year of extension growth, while the number of needle fascicles correlates with the temperature of the previous summer, when the fascicles were formed. Two methods were developed to determine the flexibility and breaking strength of pine branches. Flexibility always depends on branch diameter, and is greater for arborescent P. cembra and low-altitude P. mugo than for P. pumila and high-altitude P. mugo. Ecologically crucial is the fact that the breaking strength of high-altitude P. mugo is considerably greater than that of low-altitude P. mugo and P. cembra (fig. 2-4). P. mugo is anemochorous. P. pumita, like its parent species P. cembra, forms cones which remain closed; the seeds are dispersed by animals, in particular the nutcracker, Nucifraga caryocatactes (in Asia the subspecies macrorhynchos). We found bunches of 2 to 8 young plants in the Faurio-Caricetum blepharicarpae of the Naeba Mountains. They were all 8-9 years old, with suggests regeneration in regular periods several years apart. The occurrence of krummholz in only one association in each region (Vaccinio-Pinetum pumilae Maeda et Shimazaki 1951 in Japan and Rhododendro-Mugeturn Br.-Bl. 1939 em Oberd. 1957 in Europe) testifies to its uniformity. The actual extension of krummholz is far closer to its potential in the Japanese Alps than in Europe, where alpine dairy farming has directly or indirectly worked to destroy or at least carve up much of the former cover. The relative altitudes differ: in Europe the spatial interdigitation with the coniferous trunk-wood belt is much greater; in Japan the upper reaches are in permafrost. The three-layer structure of the two associations (Pinus sp., Ericaceae, cryptogams) is similar, but species richness is greater in European krummholz because of less dense overstoreys and greater ligth penetration. The Vaccinio-Pinetum pumilae is a pure Vaccinio-Piceetea association, whereas the Rhododendro-Mugetum is transitional to the Erico-Pinetea, in which class we place it. This reflects the different synevolutionary origins of the communities concerned. The Vaccinio-Pinetum pumilae comprises species of nordic distribution, presumably descended from the Arctotertiary flora, with only rhododendron possibly descended from the subtropical "laurel forest" flora. In contrast, the Rhododendro-Mugetum contains (in addition to the nordic species) a substantial number of Alpine species. The Vaccinio-Pinetum pumilae is often bordered by lower, fringing "Zwergmantel" formations, which belong to the Arctoo alpini-Vaccinietum uliginosi or Arcterio nanae-Loiseleurietum procumbentis, depending on wind exposure. In the northern Calcareous Alps of Europe Rhododendron hirsutum or Rh. ferrugineum also form such fringe communities, but their interdigitation with the krummholz makes them difficult to distinguish for purposes of recording and syntaxonomy. One can read a "relative ecology" from the contact communities (Fig. 5): both communities appear to require a "medium" covering of snow which allows a vegetation period of, we estimate, at least four months but also offers some protection against winterdesiccation. Their edaphic demands differ: the Vaccinio-Pinetum pumilae occurs on siliceous rock and the Rhododendro-Mugetum on limestone, though often with a covering of autogenic acidic litter. The variety of grassland communities and grass species is far smaller in the Japanese Alps, as is discussed herein