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Home » Guides » Community Warfare » Scouting Mode Strategy Guide
While I have been having more fun with Scouting Mode than Invasion Mode since its release (for the most part), it is not nearly as deep or complicated and so I feel comfortable putting basically all of the styles of Guide I wrote for Invasion Mode into a single piece for Scouting. I tried to keep it all useful for both solo queue and group play, but some parts do kind of require some coordination between you and your teammates. But now, let's cover the best strats to use in this mode, and the best mechs for accomplishing these goals!
There's a lot of weird shit going down in Scouting, but if you just want to know which mech will reliably do the best job for you…
For Clans, IFR-D. For IS, BJ-1X.
Smoke Dive
This is the Scouting Mode's equivalent of an Invasion Mode light rush. Way more effective than it has any right to be, takes advantage of uncoordinated or newer teams, and really quite boring. But it is also the most important to understand, as it has the greatest impact on how you play the other strats, and in order to understand the strat you need to understand Scouting Mode's win conditions. Obviously, you're best off reading through that section of the patch notes, but I'll go over a few of the more relevant details:
The attacker's ("Secure Intel") win condition is to get picked up by the dropship.
The dropship will come when either the attacking team collects 10 intel points, the defending ("Defend Intel") team collects 11, the clock hits 3 minutes, or the defending team is all dead (that last one is kind of irrelevant when we're discussing smoke dives, unfortunately). There is first a minute-long blue countdown where the dropship is on approach, and then a red countdown while it waits for a minute and 15 seconds, with blue beams firing at any defenders.
In order for the dropship to pick up the attacking team (without the defenders being dead), at least one of the members of the attacking team must be in the "cap" underneath the dropship when the second, red timer hits exactly 0:00.
In accordance with those rules, you can take 4 lights, spread out to the four corners of the map (collecting intel along the way of course), and make a mad dash to the dropship in an attempt to arrive just before the timer runs down to 0:00. And honestly, the hardest part of the strategy is getting the timing just perfect – you ideally want to spend as little time in the open as possible, meaning that you want to arrive at the cap (ideally) right as it runs out. This will always take some feeling out, but as a good rule of thumb, a 150KPH mech can cover a grid square (end-to-end, not corner-to-corner) in about 12 seconds. You'll also have to figure things like terrain into your calculations though, so I'd recommend counting it as more like 15 to 20.
In the end, you'll want to hide a few grids away from the pick-up point, wait until the clock has ticked down to an appropriate level, and then making a mad dash for the point. Don't stop, don't let up, just do the necessary evasive maneuvers and try to survive. It is likely that a few of you will be legged and executed on approach, but only one needs to make it for the victory to be counted and the intel points awarded.
Clearly this is an issue that needs addressing, and I must implore you to not use this tactic (honestly, it's just boring and/or frustrating for both teams), but you need to at least be aware of it.
IS Mechs
You've gotta understand, probably around half of the IS light mechs are very capable of smoke diving, so I'm just going to highlight the few which I feel make the most sense in this role.
Pirates' Bane: This mech is the most popular one you'll see for this tactic – it's ridiculously fast, it has ECM, it's decently hard to hit, has 16 extra armor on each leg, and even gets a C-Bill bonus (though if you're using this strat I doubt you're in it for the C-Bills).
CDA-3M: Its tankiness and ECM help you survive on the point (and approach to the point), but it lacks some of the speed and subtlety of the Locust. Still pretty good at this though, and worth looking out for.
SDR-5D: This ticks a lot of the same boxes as the Pirates' Bane, but runs a fair bit slower. This impedes its ability to rush down points and rush to the dropship, but it's a great non-hero option and the jumpjets help.
SDR-5K: Now we're getting into mechs which could better be described as capable of smoke diving rather than limited to it. It retains all of the qualities that make the Pirates' Bane good except for the ECM, but picks up actual combat effectiveness in the process of losing that ECM.
Oxide: Yeah, I suppose this mech can smoke dive if it decides not to kill you first. Really not optimized for this style, but it's still solid at it.
Clan Mechs
The Clans are left with relatively few options, but you're still more than capable of running the strat.
Arctic Cheetah: This is the obvious choice. It has speed, ECM, good hitboxes, and is almost as powerful a mech as the Oxide. The issue is that it runs about 25 KPH slower than its IS competitors, making it a fair bit worse at this role. I'd probably place it on the same level as the SDR-5K in terms of competence in this strat.
JR7-IIC-A: This is here because it is the fastest and most maneuverable Clan mech in the game. It lacks the ECM and the hitboxes of the Arctic Cheetah, which I feel makes it less capable in this role, but it's very fast and can hold its own if it has to fight.
IFR-D: It doesn't have the ECM or hitboxes of the Arctic Cheetah, or the speed of the JR7-IIC-A, but it's still serviceable and is the most combat-ready of the bunch. I don't think it is at all optimized for the smoke dive, but it's an option.
Anti-Smoke Dive
Now that you know the strat, let's discuss how to counter it. There are actually a few ways to go about it, but the best way is to start searching for (and killing) enemy mechs ASAP. For this reason, you'll want to start wolf-packing down isolated mechs right off the bat, and your team will need fast mechs to accomplish this.
Alternatively, you could start out by capping. For this to work, you need to be confident that your team can cap 10 points and find an eleventh to camp before the enemy team. Camping this last intel point forces the enemy team to either come to you before the dropship arrives…or wait until it comes based on the game timer. If the enemy team is really dedicated to the smoke dive, they'll just wait 10 minutes until the dropship comes automatically, but if you're lucky they'll get impatient and engage on a losing fight, or sacrifice mechs to distract you. Even if you can't cap 10 and find an 11th to camp, capping points early decreases the number of points that are available for the enemy, extending the length of the match and giving your team more time to find the enemy mechs and kill them before a smoke dive even becomes an issue. And most of the time, the enemy will have an advantage in capping so you will be forced to just hunt them down while they search for intel points. The problem with this strat is that if you can't get to the first 11 points before the enemy gets to the first 10…you've failed.
Assuming you haven't managed to eliminate the entire enemy team before they trigger the dropship, you'll have to scramble to find it if they want a chance in hell of stopping the smoke dive. Fortunately, some beautiful people have done the testing and found the locations where dropships can spawn:
Caustic Valley: B5, C2, E2, E5
Forest Colony: E8, H7, H12, I10/J11
Grim Plexus: C3, E5, F9, I3
Polar Highlands: H10, J7, J10, H7(?)
River City: D5, E8, E2, H7
So, once the blue countdown starts, run to look around those rough locations and check for green smoke. Once you find the correct location, you want to spend a good amount of time searching the nearby cover for enemy mechs in an attempt to thin out their numbers a bit more before the smoke dive begins. By the time the timer hits around 20 seconds, you'll generally want to have most of your team back near the point, ready to focus down legs as soon as they're spotted. And that legs thing is vital – as long as they're a decent way from the cap, you can just leg them and leave them for later. Ideally, by this point of the match, you'll have already found and killed a couple and damaged the others so that you can do a clean sweep as they approach. If not, you're going to have quite a tough time focusing them all down in time, but it's still possible.
The problem with this is that, if you don't find the enemy mechs in time, you won't be able to kill them in time and you'll lose. And finding these mechs can be very difficult and risky because, depending on the map and location, you could have a dropship with ER Large Lasers shooting you the whole time. So, while it's certainly possible to beat a smoke dive, it's very difficult without just having better coordination than the attackers.
The IS mechs are left on the weaker side of anti-smoke diving mechs, which is fortunate for Clan vs. IS balance because they're the best at diving.
Oxide: You need a fast mech that can kill other fast mechs. While the Oxide is best known for destroying bigs, it's more than competent against light mechs thanks to its fast missiles, tight spread, and devestating DPS. Other traditional IS lights work here too (FS9-S, FS9-A, CDA-3M lol), but the Oxide does it best from what I've seen.
BJ-1X: This variant is excellent for its ability to quickly leg mechs, and if you really want to focus on that aspect you can switch to a Med Pulse build. But with the meds, you can scrape armor off at around 600 meters, scaring off enemy smoke divers. The main issue is that you won't be able to scout out enemy positions in this mech, so you'll rely on your team for that.
Comparatively, the Clan mechs are optimal for countering smoke dives, and have a few options at their disposal.
IFR-D: This mech is incredibly effective at seeking out and destroying enemy light mechs. Their beams will just tear off legs ridiculously fast, and if you can manage to get a wolf pack going, you'll be able to make short work of any enemy mechs that are trying to dive on the point.
Stormcrow: Streaks may be the most obvious solution, but I don't think they're the best. You can't kill the enemy quite quickly enough if they're running at the cap, and you definitely can't choose to leg them, which makes me lean towards a hybrid build, or even an SRM Brawler. But even then, if you're trying to hunt them before the actual smoke dive part, they may be able to simply outrun you.
Arctic Cheetah: This is the best mech you could bring if you're struggling with the "find the enemy" part – the jumpjets help, and the ECM makes your approach a bit less obvious. The JR7-IIC-A works well at this too, but is less potent in a fight against lights.
Just Fight Them! (Attack)
This is my favorite way to play, and the way I wish that everyone would embrace. There's really not much else to say about it other than playing it like a regular 4v4 fight. And the thing is…4v4 fights are a lot of fun. Like, a lot of fun. To me, having to plan around things like intel and smoke dives and all that crap just takes a bit of the magic away. Fortunately, on Attack, you don't have to worry about that! You can just play whatever mech you want in the tonnage range without worrying about the enemy running and depriving you of glorious combat. If you're interested in which mechs I think do best at this…well, as team sizes decrease, brawling tends to get stronger. And as mech tonnages decrease, brawling tends to get stronger. So take a look at the Competitive Tier List and take one of the medium mechs in the brawling section. You can make the other range brackets work too, so feel free to try out those, but brawling (with maybe a bit of mid-range) is just obviously the best.
Just Fight Them! (Defense)
On defense, you don't have the luxury of ignoring gimmicky smoke dive strats. Your mech choices don't have to revolve around this, as with the anti-smoke dive strat, but they really should take it into account. So what we're looking for are mechs that are generally strong enough to give you a fighting chance against opponents that actually want to have fun and fight, and fast enough to give you a fighting chance against smoke diving scum.
BJ-1X: This easily fulfills the requirements – it can play well against brawlers by getting early harass on them, and it can leg lights better than most mechs.
GRF-3M: The loss of hitscan can hurt your ability to kill lights, but the speed keeps you very relevant, and you can take on larger mechs pretty comfortably.
Oxide: It's really fast, and really powerful. It's not quite as valuable in a brawl as a big medium brawler, but it's much more flexible.
IFR-D: I really think this mech has found a bit of a niche in Scouting mode – it has great speed, lots of hitpoints, and some really sweet offensive and defensive quirks. It's hard to see anything but a group of 4 hardcore brawlers beating 4 of these (pilot skill and coordination being equal, obviously).
Stormcrow: It's not fast enough to chase down a light mech, but it can stay in range for a few alphas, which should suffice. Versus bigs, it can cause utter devastation, only matched by IS brawlers. And if you're particularly worried about lights, you can try the hybrid build I linked earlier. Or you can just bring 12 small pulse.
There are a lot of things I like about the Scouting mode, but the boredom and frustration of smoke dive matches are enough to put me off the mode for the most part. I would recommend that PGI make it so that the dropship doesn't have weapons, and make it so that the attackers have to be in the cap for a few seconds (5-10) before the game ends. The cap progress doesn't have to be blocked by the defenders, but they have to be given a good chance to repel a smoke dive, and the attacking time has to be incentivized to take mechs which are good at anything but that one gimmick.
I feel the need to point out that this is all based on my own experiences with the mode, and the knowledge of other that I've talked to. I've played in groups, I've played in solo queue, but there is a chance that my experience in those settings are going to be different than your experiences in those settings. If you disagree with me about some of my points, or find something that you know to be factually incorrect, please let me know on the forums – this is the first incarnation of the guide and while I expect it to be good, I don't expect it to be flawless.
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text:
Coniopteryx obtusa är en insektsart som beskrevs av Withycombe 1925. Coniopteryx obtusa ingår i släktet Coniopteryx och familjen vaxsländor. Inga underarter finns listade i Catalogue of Life.

Källor

Vaxsländor
obtusa

redpajama_set_name: RedPajamaWikipedia


text:
Бладшот () — вигаданий супергерой, персонаж коміксів видавництва Valiant Comics. Створений Кевіном Вангоком, Доном Перліном і Бобом Лейтоном.

Вигадана біографія
Рей Гаррісон, ідеальний солдат, Псі-вбивця, жива зброя, створена організацією Проєкт «Відродження Душі». Його організм був модифікований введенням мільярдів нанітів, мікроскопічних роботів, що дало йому надлюдські можливості.

У початковій версії біографії, Бладшот від початку виступав мафіозним кілером на ім'я Анджело Морталлі, якого піддали нанотехнологічної експериментів вчені проекту Сонце,що сходить. У сучасній версії біографії він є колишнім солдатом і секретним агентом на ім'я Реймонд Гаррісон, який загинув на війні і воскрес за допомогою нанотехнологій, що дали йому надздібності, але при цьому втратив пам'ять,яку наповнили фальшивими спогадами. Певний час вчені використовували його в своїх цілях, але потім Рей почав згадувати фрагменти свого минулого і втік від Сонця,що сходить,ставши супергероєм.

Історія публікацій
Бладшот був створений у 1992 році. Ім'я було вигадано Девідом Члістеком, коли комікс Valiant Universe був на хвилі популярності. Дебютував Бладшот на сторінках коміксів у листопаді 1992 року. Як один з самих популярних персонажів Valiant, Бладшот підсилював свій успіх, продаючи з кожним місяцем все більше копій коміксів, поки видавництво Valiant не викупили за 65 мільйонів доларів Acclaim Entertainment. Комікси були перекладені більш ніж 15 мовами, включаючи французьку, німецьку, італійську, іспанську, норвезьку, філіпінську, китайську, турецьку та інші. У 1996 році Бладшот і більшість других персонажів всесвіту Valiant були перевипущені під стягом Acclaim Comics. Повторний запуск означав, що комікси рухаються у новому направленні, яке згодом буде легше адаптувати до відеогри. Valiant Entertainment й зараз є власником каталогу персонажів Valiant.

Новий том «Бладшота» був випущений у липні 2012 року, написаний , після перезавантаження Valiant Comics. Ще один новий том був випущений 9 вересня 2015 року під назвою «Бладшот: Відродження».

Критика
Комікси про Бладшота стали найдорожчими з серії  Valiant. Спільний обсяг продажу досяг семи мільйонів копій. Незадовго до свого дебюту, Бладшот з'явився в ще одних відомих серіях про супергероїв: «Рай» і «Eternal Warrior». Саме через це, компанії довелось створити  повноцінний комікс «Bloodshot» #1 у лютому 1993 році. Сольник Бладшота був дуже  очікуваним серед фанатів,  тому було продано більш ніж мільйон копій. Оригінальна серія була написана Кевіном Вангоком і намальована Доном Перліном. У прем'єрі з'явилась перша обкладинка до коміксу «Chromium».

«Bloodshot» #1 випущений у липні 2012 року був нагороджений «Найкращим коміксом» за версією  Diamond Comic Distributors (кращий дистриб'ютор американської комікс-індустрії)  й  отримала гран-прі за найкращу обкладинку. «Бладшот» був названий одним з десяти найкращих коміксів 2012 року за версією Nerdage.

Поза коміксом

Фільм
У березні 2012 року  Columbia Pictures придбала права на екранізацію коміксу «Бладшот» від Valiant Comics. В квітні 2015 року Valiant, Sony і Original Film оголосили про спільне створення серії з п'ятьох фільмів, щоб перенести всіх супергероїв всесвіту Valiant Comics на великий екран. Перші два фільму будуть про Бладшота, наступні два --  про «Віщуна»,а останні два -- кросовери між двома супергероями. Головну роль у фільмі виконає Він Дізель.

Відеогра

 Бладшот є секретним персонажем гри Shadow Man, якого потрібно розблокувати як персонажа у версіях для Nintendo 64 і Dreamcast.
 Про Бладшота повинна була вийти окрема комп'ютерна гра, розробкою якої повинні були займатися Iguana Entertainment UK для PlayStation і Microsoft Windows, але гра була призупинена на деякий час  видавцем Acclaim Entertainment, щоб зосередитися на інших іграх.

Вебсеріал
Бладшот з'являється у вебсеріалі «Ninjak vs. Valiant Universe» у виконанні .

Примітки

Посилання

 Бладшот на Valiant Comics вики
 Бладшот Фан-сайт
 "Valiant Days, Valiant Nights - A Look Back at the Rise and Fall of Valiant, Newsarama

Супергерої
Вигадані солдати
Valiant Comics
Вигадані вбивці
Персонажі коміксів з прискореним зціленням
Персонажі коміксів з надлюдською швидкістю
__ІНДЕКС__
__ПОСИЛАННЯ_НА_НОВИЙ_РОЗДІЛ__


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The 2000 Masters Tournament was the 64th Masters Tournament, held April 6–9 at Augusta National Golf Club in Augusta, Georgia. Vijay Singh won his only Masters, three strokes ahead of runner-up Ernie Els. It was the second of Singh's three major titles.

Course

Field
Each player is classified according to the first category by which he qualified, with other categories in which he qualified shown in parentheses.

1. Masters champions
Tommy Aaron, Seve Ballesteros, Gay Brewer, Billy Casper, Charles Coody, Fred Couples (16,17), Ben Crenshaw, Nick Faldo, Raymond Floyd, Doug Ford, Bernhard Langer (10), Sandy Lyle, Larry Mize, Jack Nicklaus, José María Olazábal (16,17), Mark O'Meara (3,16,17), Arnold Palmer, Gary Player, Craig Stadler, Tom Watson, Tiger Woods (4,11,14,15,16,17), Ian Woosnam (10), Fuzzy Zoeller
George Archer, Jack Burke Jr., Bob Goalby, Herman Keiser, Byron Nelson, Sam Snead, and Art Wall Jr. did not play.

2. U.S. Open champions (last five years)
Ernie Els (14,16,17), Lee Janzen (10,16,17), Steve Jones, Corey Pavin
Payne Stewart, the 1999 U.S. Open champion, died in a plane crash in October 1999.

3. The Open champions (last five years)
John Daly, Paul Lawrie (16,17), Tom Lehman (14,16,17), Justin Leonard (5,13,14,16,17)

4. PGA champions (last five years)
Mark Brooks, Steve Elkington (10,14,16,17), Davis Love III (10,14,16,17), Vijay Singh (11,14,16,17)

5. The Players Championship winners (last three years)
David Duval (10,11,14,16,17), Hal Sutton (11,14,16,17)

6. U.S. Amateur champion and runner-up
David Gossett (a), Kim Sung-yoon (a)

7. The Amateur champion
Graeme Storm (a)

8. U.S. Amateur Public Links champion
Hunter Haas (a)

9. U.S. Mid-Amateur champion
Danny Green (a)

10. Top 16 players and ties from the 1999 Masters
Bob Estes (14,16,17), Carlos Franco (14,16,17), Jim Furyk (14,16,17), Brandt Jobe, Phil Mickelson (11,14,16,17), Colin Montgomerie (16,17), Greg Norman (16), Steve Pate (14,16,17), Nick Price (14,16,17), Lee Westwood (16,17)

11. Top eight players and ties from the 1999 U.S. Open
Tim Herron (14,16,17), Jeff Maggert (14,16,17), Steve Stricker (16,17)

12. Top four players and ties from 1999 PGA Championship
Stewart Cink (14,16,17), Sergio García (16,17), Jay Haas

13. Top four players and ties from the 1999 Open Championship
Ángel Cabrera, Craig Parry (14,16,17), Jean van de Velde

14. Top 40 players from the 1999 PGA Tour money list
Stuart Appleby (16,17), Notah Begay III, Glen Day (16,17), Fred Funk (16), Brent Geiberger (16,17), Scott Gump, Dudley Hart (16,17), Gabriel Hjertstedt, Scott Hoch (16,17), John Huston (16,17), Skip Kendall, Rocco Mediate, Jesper Parnevik (15,16,17), Dennis Paulson, Chris Perry (16,17), Loren Roberts (16), Jeff Sluman (16,17), David Toms (16,17), Ted Tryba, Duffy Waldorf, Mike Weir (17)
Since Payne Stewart finished in the top 40 of the money list, an invitation was given to Hjertstedt, the 41st-place finisher.

15. Top 3 players from the 2000 PGA Tour money list on March 5
Kirk Triplett (17)

16. Top 50 players from the final 1999 world ranking
Thomas Bjørn (17), Darren Clarke (17), Retief Goosen (17), Pádraig Harrington, Miguel Ángel Jiménez (17), Masashi Ozaki (17), Naomichi Ozaki (17), Bob Tway (17), Brian Watts (17)

17. Top 50 players from world ranking published March 5
Paul Azinger, Shigeki Maruyama

18. Special foreign invitation
Aaron Baddeley (a)

All the amateurs except Danny Green were playing in their first Masters, as were Notah Begay III, Ángel Cabrera, Brent Geiberger, Pádraig Harrington, Skip Kendall, Paul Lawrie, Dennis Paulson, Jean van de Velde, and Mike Weir. Sergio García made his first appearance as a professional.

Round summaries

First round
Thursday, April 6, 2000

Second round
Friday, April 7, 2000

Amateurs: Gossett (+2), Baddeley (+5), Green (+5), Kim (+6), Haas (+9), Storm (+15).

Third round
Saturday, April 8, 2000
& Sunday, April 9, 2000

The third round was suspended by darkness due to two-hour rain delay and completed on Sunday morning.

Final round
Sunday, April 9, 2000

Final leaderboard

Sources:

Scorecard

Cumulative tournament scores, relative to par
{|class="wikitable" span = 50 style="font-size:85%;
|-
|style="background: Pink;" width=10|
|Birdie
|style="background: PaleGreen;" width=10|
|Bogey
|}
Source:

References

External links
Masters.com – past winners
Coverage on the European Tour's official site
Augusta.com – 2000 Masters leaderboard and scorecards

2000
2000 in golf
2000 in American sports
2000 in sports in Georgia (U.S. state)
April 2000 sports events in the United States


text:
package hr.droidcon.conference.utils;

import android.content.Context;
import android.os.Build;
import android.util.DisplayMetrics;

/**
 * Utility class
 * @author Arnaud Camus
 */
public class Utils {

    public static int dpToPx(int dp, final Context ctx) {
        if (ctx==null || ctx.getResources() == null) {
            return 0;
        }
        DisplayMetrics displayMetrics = ctx.getResources().getDisplayMetrics();
        return (int)(dp * (displayMetrics.densityDpi / 160f));
    }

    public static int pxToDp(int px, final Context ctx) {
        if (ctx==null || ctx.getResources() == null) {
            return 0;
        }
        DisplayMetrics displayMetrics = ctx.getResources().getDisplayMetrics();
        return (int)(px / (displayMetrics.densityDpi / 160f));
    }

    public static boolean isLollipop() {
        return Build.VERSION.SDK_INT >= Build.VERSION_CODES.LOLLIPOP;
    }
}

redpajama_set_name: RedPajamaGithub


text:
Have we reached the end of globalization?
For more What in the World watch Sundays at 10 a.m. & 1 p.m. ET on CNN
By Global Public Square staff
At the start of 2014, let's take a look at one of the great trends of the last century. You could be sitting in Chicago, Illinois right now, but your TV was probably made in Japan, your sneakers were likely manufactured in China and your coffee might be from Kenya. Globalization impacts every single thing around us. So here's the big question: have we reached the end of globalization?
For much of the last thirty years there has been a steady trend in commerce: global trade has expanded at about twice the pace of the global economy. For example, between 1988 and 2007, global trade grew on average by 6.2 percent a year according to the World Trade Organization. During the same period, the world's GDP was growing at nearly half that pace: 3.7 percent.
But a strange thing has taken place in the last two years. Growth in global trade has dropped dramatically, to even less than GDP growth. The change leaves one wondering: has the incredible transfer of goods around the world reached some sort of pinnacle? Have we exhausted the drive toward ever-more-globalization?
It's a fascinating thesis. The world has seen historic developments in the last few decades: the internet, China's opening up, the rise of emerging markets, fast and cheap travel…all of these trends led to a massive acceleration in global trade.
But have those trends peaked? Could the next big invention, say, 3-D printers, end the need for more and more trade? Imagine a world where you need a new faucet in your restroom. Instead of going to the local store that sells faucets made in China (which contributes to global trade) now you just print out your own faucet, sitting at home or at a local store. Are people also getting more interested in local products compared to global brands.
Joshua Cooper Ramo points out in an essay in Fortune that localism is on the rise – local banking, local manufacturing, and even local sourcing for food and restaurants. Is this simply a pause or could it be more than that? The answer will depend on politics.
The last time the world saw a consistent period where the growth of global trade lagged behind global growth was in the 1920s, 30s, and 40s. One factor was the rise in protectionist policies - as a response in many cases to the Great Depression and the disruption of the gold standard. At one point, under what was known as the Smoot-Hawley tariff, the United States government began imposing import duties of around 60 percent. The move was aimed at protecting domestic farmers, but instead, it exacerbated the depression. It led to a steep drop in trade, and a wave of counter protectionist measures by other countries.
The world has learned its lessons from the Great Depression. But perhaps not as well as it should have.
According to the independent think tank Global Trade Alert, we're in the midst of a great rise in protectionism. In the 12 months preceding May 2013, governments around the world imposed three times as many protectionist measures than moves to open up. Anti-trade policies are at their highest point since the 2008 financial crisis. According to the Petersen Institute, the rise of these measures cost global trade 93 billion dollars in 2010.
There might be some good news on this front. Last month, the World Trade Organization passed a deal to cut red tape in customs. It's a small start, and there is a lot more to accomplish. Globalization and trade have produced huge benefits for people, especially the poor, who have been able to make their way out of poverty in a faster growing and more connected global economy. But globalization won't continue by accident or stealth – politicians will have to help make it happen.
Topics: Economy • Global • What in the World?
Next entry »Can China reform in time?
« Previous entryOn GPS Sunday: What will 2014 bring? Plus, Bono and Elon Musk on creativity
It's the over consumption by the people in the first world, rather than an over populated world
Travis B
I don't think that trade will ever completely stop. In America we look for the cheapest goods,so that why we wouldn't stop trading.Also when you are in business you look for the cheapest way to make your good,so if you let the Chinese make your good and get it for 50 cent a piece it's better than if you stay local and pay the American works 75 cent to a dollar piece.one thing that concerned me is when it said "the last time the world saw consistent period were the 1920,30,and 40s." I don't know a lot about globalization but I know a lot about history and in history those years were the years of the Great Depression.
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redpajama_set_name: RedPajamaCommonCrawl


text:
module Tunnel
  class Configfile
    class << self

      def configs
        @configs ||= ( load_from_file || [] )
      end

      def load_from_file
        return false unless config_exists?

        if result = YAML.load_file(configfile)
          result.map { |c| Config.new(c) }
        else
          puts "Your tunnel config (~/.tunnel) is not valid yaml"
        end
      end

      def add(config)
        configs.push(config)
        save
      end

      def save
        File.open(configfile, "w+") do |f|
          f.puts YAML.dump( configs.sort_by { |c| c.name } )
        end
      end

      def config_exists?
        File.exist?(configfile)
      end

      def configfile
        File.expand_path("~/.tunnel")
      end
    end
  end
end


I ran my first 10K today.
It was hard, but good.
I was passed, and I passed others.
The tips of my toes hurt and my legs are tired, but I wanna get up and go do something.
I ran/walked 6.2 miles in 1 hour 16 minutes (according to the running app on my phone).
I jogged the entire first mile! Then I walked and lost that momentum.
I'm really hungry now. Time for some protein and to relax for a bit.
OMG - I went 6.2 miles! That's the farthest I've ever gone! Tee hee!
Great job on your run! I hope to be there next year!


Many of Southern California's rentals are single family homes, but multifamily properties are also quite common. These properties can include duplexes with multiple tenants, apartments in a large building, condominiums with shared common spaces, and homes with multiple levels. Whether you're responsible for a single unit or every tenant in the building, it's important to thoroughly address all of the responsibilities on your plate.
At Real Property Management, we work with multifamily property owners across North San Diego County, both on the coast and inland. We've cemented ourselves as a pioneer in the property management industry over the course of our 40-year history in San Diego. Our team works diligently to provide services that keep our clients profitable, without sacrificing the satisfaction of tenants. From finding the right renters to handling maintenance and accounting needs, our team has you covered. We'll even address specific challenges like evictions and late rent payment collection.
The wrong tenant could cost you thousands of dollars in lost revenue and damages. Don't be blindsided by someone who doesn't respect your investment. RPM's marketing team works diligently to locate the best tenants in our area. We use high-quality photographs to catch the eye of interested applicants, and we schedule showings quickly.
RPM renters must meet our strict standards to be considered for one of our homes. Our financial requirements help ensure tenants will make rent each month. We also verify criminal background and rental history information, which helps us to make the right decision for your home. Finally, we'll handle the lease drafting and signing for you.
Nobody wants to interrupt dinner or wake up to an emergency maintenance call, but repairs are part of life for most landlords. By entrusting your property to our team at RPM, you won't deal with the hassle of maintenance calls ever again. We provide 24/7 emergency support for our tenants, so you never have to be on call. Going on vacation or simply want to enjoy your weekend in peace? We've got you covered.
We don't only answer maintenance calls quickly, but we also save you money. We've negotiated preferential rates with our trusted network of licensed vendors, and we pass along the savings to you. All of the work we perform meets local building codes and ensures your property will remain healthy for years to come.
Never sort through endless piles of bills and financial statements again. RPM will work to address all of the monthly accounting needs of your multifamily property. We handle rent collection and allow tenants to pay us directly online, which helps expedite the process. All earnings are disbursed quickly via direct deposit, which helps protect your cash flow.
Best of all, you can easily access your account information around the clock by logging in to our convenient owner portal. Review your financial statements in just a few clicks—it's the easiest way to monitor your account, even when you're traveling out of state. You can also use the portal to update your information, review inspection notes, or get in touch with our team.


According to the researchers at Rocky Mountain Institute, there are a variety of strategies -- from better utility and stakeholder collaboration to a focus on new technology that can scale -- that could help with the problem. RMI recently published a report that digs into a handful of possible solutions that utilities, regulators, tech companies, customers and environmentalists can use to try to get the energy sector to evolve more quickly and effectively.
RMI decided to tackle the topic in a report after working with New York utility Con Edison, which was looking to launch some demonstration projects with new technology, explains RMI's electricity practice manager, Mike Henchen. "A lot of utility projects are not that effective, and a lot of projects are just pilots, and a lot don't lead to full-scale deployments," he said.
1) Change is coming, so deal with it intelligently: With the introduction of distributed energy technologies -- solar panels, batteries, electric car chargers and smart thermostats -- the power grid is already transforming. Utilities need to fully embrace and plan for this change, and need to develop road maps and support from leaders for how to navigate these changes.
2) Pilots and demos need to be designed to scale: One of the biggest takeaways from the report is that many times, utilities' pilot and demonstration projects don't lead to useful conclusions and are largely ineffective. RMI says if utilities focused on making the end goal to scale effective technology to their entire network, then their trial runs would be more productive.
Utilities should test out newer technology in small pilot projects that can determine if the tech is useful or not. If it isn't, utilities can shut down those projects and learn from the deployment. "Failure consists of running a pilot or demonstration project and coming away with inconclusive results, or failing to identify and capture important lessons," states RMI in the report.
If technology is found to be useful, utilities can use larger demo projects to deploy proven tech and experiment with business models and strategies. "Learnings need to lead to decisions," the report states.
If pilot and demo projects don't lead to decisions, it can lead to fatigue on the part of the tech vendors participating, the regulators overseeing the projects, and the staff at the utilities working on the projects. Plus, it's just a waste of time and money.
3) Better leadership: Utilities should have company leaders participate in and oversee innovation projects. The RMI report found that often interesting innovation takes place at utilities, but it's siloed within small groups.
For innovation to be effective across the company, it needs to be supported by leaders of the company, and it needs to involve a variety of business groups early on to ensure the change sticks. Utilities should also find ways to engage new and young employees and not only task the old guard with managing innovative projects.
4) Engage with stakeholders early: When utilities are building pilot and demo projects, they need to work collaboratively with the variety of stakeholders that will be affected by the initiative. That includes regulators, customers, environmentalists and technology providers.
If utilities don't take these actions, certain stakeholders that feel excluded can block aspects of a project. Regulators and customers can be unnerved if rates rise, and advocates can push back if environmentally sensitive regions are used without agreeing on common ground.
The RMI report also advises that when utilities are looking for new pilots and demos that they design their requests for information or requests for proposals to be neither too prescriptive nor too vague. To get the best results, project solicitations should be clear and but not so detailed that they arbitrarily limit the solutions offered.
5) Collaborate with other utilities: The utility industry is in the unusual position of not having to compete with other utilities in most scenarios. Thus, it should be natural that utilities share lessons learned with each other and use case studies to evolve more efficiently. However, utility collaboration is relatively rare.
Third-party researchers and regulators can help spur this process by seeking out information and synthesizing the most important learnings. RMI's Henchen said that in some ways, there's energy information overload with so many conferences and reports, and it can be difficult to break through the noise and find what's truly useful. Researchers have an important role to play in curating the information provided by utilities to highlight major takeaways and key metrics, targeted at specific concepts and business models.


text:
Molecular Researchers Investigate Cellular Stress to Combat Diseases
Research Findings Published in Scientific Reports
Nikolas Nikolaidis, center, associate professor of biological science, and student researchers Peter Nguyen, left, and Ryan Oliverio investigate cellular stress response in his molecular biology lab on campus.
Discovering Research
Students in the lab of Nikolas Nikolaidis, associate professor of biological science, discuss the benefits of doing research.
Kyle Hess: "Conducting research as an undergraduate puts you in the driver's seat of scientific discovery and teaches you to apply concepts from classes to new situations. The research environment at CSUF fosters creativity and critical thinking, both of which are valuable skills that help in academics and in today's workforce."
Ryan Oliverio: "By observing and working with Dr. Nikolaidis, I learned essential skills that you cannot learn in a classroom, such as how to lead a diverse group of individuals, how to effectively troubleshoot a problem, how not to sell yourself short — and so much more."
Peter Nguyen: "The benefits are incalculable. To be able to work on a research project allows an individual to develop in-depth thinking processes. Dr. Nikolaidis has been very patient with me since day one, and has spent endless hours going over experiments — until I am confident enough to perform them on my own."
In everyday life, people are bombarded by stressful factors from the environment: radiation from the sun, a fever caused by viral infections or carcinogens that cause cancer.
"Without intervention, these factors can disrupt cellular processes, and eventually lead to a host of different diseases," said Ryan Oliverio, who earned his master's degree in biology this year.
Under the mentorship of Cal State Fullerton molecular biologist Nikolas Nikolaidis, Oliverio and fellow student researchers are investigating a particular molecule found in stressed cells known as "heat shock protein." Their research focuses on finding out how these cells respond to environmental stress due to heat, toxins and even cancer.
"This heat shock protein plays a critical role in the ability of our cells to resist, adapt and survive stress," explained Nikolaidis, associate professor of biological science. "However, this particular protein can be a friend or a foe. It can help you recover from a fever, but it can also help to keep cancer cells alive."
Using bioinformatics tools and biochemical experiments, the researchers discovered how these crucial abilities of this heat shock protein were retained in humans.
"Our findings reveal the genetic mechanisms and evolutionary forces that preserve one of the most critical components of our ability to survive stress — and thrive," continued Nikolaidis, who was awarded a $417,300 National Institutes of Health grant last year for his research.
This breakthrough by Nikolaidis and his team of student researchers was published in Scientific Reports, an online multidisciplinary, open access journal from the publishers of Nature. In addition to Nikolaidis, the paper includes seven CSUF student co-authors and Dimitra Chalkia, a biostatistician and visiting scientist last year in Nikolaidis' lab from the UCLA Center for Systems Biomedicine.
Oliverio, one of the paper's student co-authors, became interested in the research to learn more about the biological mechanisms behind conditions such as Alzheimer's disease, which afflicts his grandparents.
"By understanding why we have so many stress-related proteins and how genetic variation, both natural and clinical, affect the function of these proteins will help us learn more about genetic predispositions to a wide variety of diseases, the role cellular stress proteins play on these diseases, and the importance of cellular stress proteins for an organism," said Oliverio, who starts osteopathic medical school in the fall at Touro University Nevada to pursue a career in family medicine.
Kyle Hess, another student co-author, was drawn to the research because of his interest in human evolution.
"I like the idea of combining computational research with experimental biology to understand more about our history as a species," said Hess, who earned his bachelor's degree in biological science in 2016 and is a doctoral candidate in molecular and cellular biology at the University of Washington.
"Before our project, no one had systematically looked at how this heat shock protein has changed within the human population.
"Heat shock proteins are crucial for human survival. By uncovering the evolutionary history of these proteins in humans, we are able to better understand how they may shape both human health and disease in modern times. This type of information may help future scientists and clinicians delineate the complex relationships between heat shock proteins, human health and disease."
Peter Nguyen, who earned his bachelor's degree in biological science in 2015, began doing research in Nikolaidis' lab six years ago as an undergraduate.
"Through our research, we can potentially prolong the survival of our human race," said Nguyen, also a co-author of the paper who is on track to earn his master's degree in biology next year. He plans to pursue a research career in the U.S. Army, focusing on limb regeneration.
"I hope that one day I will be able to use my knowledge and experience to combat against the diseases that contribute to the failure of cellular stress," Nguyen added.
Celebrated Reputation College of Natural Sciences and Mathematics Titan Alumni


text:
Roelens Insights
SPONSOR LICENCES: PRE-LICENCE PRIORITY SERVICES
There is some light at the end of the tunnel...
The hard-pressed Pre-Licence Priority Service purports to cut the UKVI's standard sponsor licence application processing times from 8 weeks down to 10 working days.
An accumulation of factors, notably the Pandemic, Brexit and the knock-on effects of the war in Ukraine had made it a near impossibility to obtain a slot on these priority services which were limited to 10 per day, nationwide. Many a bleary-eyed Cinderella immigration lawyer stayed up late to press "Send" as the clock struck midnight to fight for one of these precious slots for their clients, in the past. We will henceforth have access to 30 slots per day from 9am. There is hope...
Essentially, since Brexit, there has been an exponential increase in the demand for sponsor licences as these are needed to recruit migrant workers from abroad. As the nationals of 27 new countries now require visas to come to the UK to work and yet more categories have been brought within the "sponsorship regime" by the introduction of the Global Business Mobility route in April 2022, the pressure on the priority services will have multiplied manifold. However, it has taken much time for the Home Office to respond to this increase in demand.
We have shared the frustrations of other immigration lawyers as we watched the Home Office divert valuable experienced and trained staff and other resources away from the business immigration teams to deal with the Ukraine schemes and the Rwanda arrangement.
To avoid any misunderstandings: those schemes made life a misery for unfortunate and distressed Ukrainians fleeing the bombings by adding red-tape to their flight to safety and inflicted serious harm on those desperately risking their lives to cross the Channel in small dinghies. If obstacles such as the Ukraine visa schemes were really necessary, it may have been sensible, when also trying to recover from the reverberations of the Pandemic, to hire new staff and to provide intensive training to deal with such visas which are "relatively" simpler to process than divert resources away from the sponsorship licensing regime, which requires a great deal more knowledge, skill and experience.
Of course, we recognise there are far more complexities than meet the eye for those managing staff and other resources at UKVI…
Nevertheless, priorities for the UK economy need to be balanced against an inappropriate "visa" regime for those fleeing war-torn Ukraine and deploying gun boats to push back Afghans, Syrians, Iranians, south-Sudanese etc risking their lives on small boats. Most other European nations welcomed Ukraine refugees without imposing visa requirements.
In short the funds diverted to setting up the controversial and abhorrent Rwanda scheme might have been better used in supporting the business immigration teams at UKVI as a part of the measures to enable the country to get back on its feet again following the triple whammy of Pandemic, Ukraine and, Brexit…
So, what does having 30 slots mean for employers desperate to recruit skilled staff from overseas with crippling staff shortages? It may mean that there is a fighting chance of getting your sponsor licence application looked at within 10 days if you pay the additional fee of £500 for swifter processing.
The priority, however, really ought to be to channel far more resources to the Sponsor Licence teams at the Home Office to meet demand and to avoid having to need a Pre-Licence Priority Service at all. The bottle necks, delays and backlogs in business immigration and EUSS may be avoidable, if the pre-occupation with Rwanda deals and the harrowing Ukraine visa schemes are eased.
30 slots for the pre-licence priority service is still not good enough…
Author: Nilmini Roelens
FRENCH BREAKFAST: Roelens Solicitors immigration projects 2023
GRADUATE VISA OPTIONS FOR THE UK
THREE LIONS POISED TO TACKLE FRANCE: POLITICS OF SPORT


text:
Unusual manifestations of visceral leishmaniasis in children: a case series and its spatial dispersion in the western region of São Paulo state, Brazil
Luiz Euribel Prestes-Carneiro ORCID: orcid.org/0000-0002-4577-15251,3,
Patricia Rodrigues Naufal Spir2,3,
Mateus Fontanesi3,
Karen Gabriella Pereira Garcia3,
Francisco Assis da Silva1,
Edilson Ferreira Flores4 &
Dewton de Moraes Vasconcelos5
BMC Infectious Diseases volume 19, Article number: 70 (2019) Cite this article
Visceral leishmaniasis (VL) is becoming endemic in São Paulo state, in the southeastern region of Brazil. Unusual manifestations with non-specific signs and symptoms may make diagnosis difficult and delay treatment, increasing the risk of severity and death, particularly in new endemic areas. There are few studies on patients with these characteristics in Brazil. We describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state.
Cases presentation
From 2009 to 2014, five clinical cases involving children treated in the Regional Hospital of Presidente Prudente (RH) were selected. Two patients had multiple relapses requiring liposomal amphotericin B; one patient had VL-cytomegalovirus-dengue co-infection and liver injury; one patient was diagnosed with X-linked agammaglobulinemia, a primary immunodeficiency; and one patient was diagnosed with VL-human immunodeficiency virus/acquired immunodeficiency syndrome (VL-HIV/AIDS) co-infection. Primary or secondary immunodeficiencies were found in four children, and associated viral infections were found in three children. Three patients were referred from other hospitals to RH. With regard to the geographic spread of VL, more cases were found in the northern area, in the epicenter of the infection where the first cases were registered, flowing south; a spatial-temporal occurrence was found.
Primary and secondary immunodeficiencies and viral co-infectious should be considered among unusual manifestations of VL, especially in those with multiple relapses. Spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.
VL is considered a neglected disease, with a higher prevalence in subtropical and tropical regions. In 2013, in Latin America, Brazil harbored 96% of cases, with most of the infected individuals living in the northeast region. In recent years, the disease has been spreading fast and has been reported in humans or dogs in 26 Brazilian states, with 19 states reporting cases of autochthonous human VL [1]. In 1996, infected dogs and humans were found in Araçatuba in the northwest of São Paulo state, and in 2006 the disease reached the western region, with 45 municipalities and about 900,000 inhabitants [2, 3]. These municipalities comprise the Regional Health Assistance Network11 (RRAS11), located in Presidente Prudente's mesoregion. In this region, from 2006, when the first human case was reported in Dracena, a city with high transmission rates, to 2017, 18 of the 45 municipalities reported 492 human cases and 27 deaths, a lethality rate of 5.5% [4, 5]. The vector of VL, Lutzomyia longipalpis was found in 34 municipalities and canine VL was found in 28 municipalities [5].
In endemic areas of developing countries, about 50% of individuals treated for VL may be children [6]. VL is a long-term febrile disease and the clinical signs are non-specific and characterized by fever, paleness, weight loss, increased abdominal volume, hepatosplenomegaly, and edema. In new endemic areas, because of the non-specific signs and symptoms, VL can be misdiagnosed with delay in treatment, increasing the severity of the disease [4]. There are few studies on patients with these characteristics in Brazil. In this scenario, tertiary public hospitals play a key role in the Unified Public Health System throughout Brazil. They support smaller hospitals and more complex treatment procedures are performed [4]. Spatial analytic techniques have been used as valuable tools in epidemiologic studies, particularly for infectious diseases, including leishmaniasis. They can denote the points of occurrence and the intensity of certain phenomenon, helping public health authorities in their strategies for control and preventive measures. Furthermore, they can predict the dispersion of parasites and vectors and the influence of the neighborhood in the spread of the disease [2, 3, 7]. Here, we describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state, considered a new focus of VL in Brazil. Cases were selected based on unusual manifestations in the emergency room, unexpected evolution on treatment, or rare co-morbidities/co-infections.
Case series presentation
On February 22, 2014, a 24-month-old girl referred from Dracena's municipal hospital (Fig. 1, number 1) was admitted to RH and her parents related that she had had a fever for 10 days. In the previous 3 days, her health had worsened significantly with adynamia, pallor, inappetence, oliguria, and choluria. On systematic examination, she was lethargic, her skin was discolored (4+/4+), and hypoactive. A radiographic image on admission suggested pneumonia. Complete blood count showed marked anemia, thrombocytopenia, and a significant increase in hepatic enzymes (Table 1, column 1). Abdominal ultrasonography showed pronounced hepatosplenomegaly. Supported by her health status, laboratory and image examinations, and the fact that she lived in an endemic region, VL was suspected. The laboratory diagnostics (Table 1, column 1) recommended mainly by the Manual of Surveillance and Control of Visceral Leishmaniasis of São Paulo state [8,9,10,11] included direct parasitology consisting of the presence of amastigotes of Leishmania in bone marrow aspirate stained by Giemsa stain; a serological titer ≥1:80 in an indirect fluorescent antibody test (IFAT; Bio-Manguinhos/FIOCRUZ, Rio de Janeiro, Brazil); and in 2010, the rK39 rapid diagnostic test (Kalazar Detect, InBios, Seattle, Washington, USA) was implemented. She was sent to the pediatric intensive care unit (ICU) from the emergency department and treated with liposomal amphotericin B (5 mg/kg/day) for 5 days. Serology screening showed that she was positive for cytomegalovirus (CMV) antibodies IgG and IgM. At the end of VL treatment, she had severe liver injury, presenting hyperbilirubinemia, hypoalbuminemia, and increased liver and canalicular enzymes: alanine transaminase (ALT) 354 IU/mL; aspartate transaminase (AST) 401 IU/mL; alkaline phosphatase 993 mg/dL; γ-glutamyl transferase 1048 mg/dL; total bilirubin 5.77 mg/dL, leading to fecal acholia, jaundice, and hypoalbuminemia (2.7 g/dL). Because there was an outbreak of dengue fever in her home region, dengue was suspected and IgM serology was positive in two different samples. She remained in the pediatric ICU for 12 days and was discharged after 24 days. At discharge, the case was diagnosed as VL-CMV-dengue virus co-infection and liver injury, and she was followed for 1 year as an ambulatory patient with pediatric infectious diseases. In March, 2017, she was hospitalized with severe respiratory distress and renal failure, remaining in the pediatric ICU; she died 2 days later with a diagnosis of Brazilian spotted fever transmitted by ticks for which the causative agent is Rickettsia rickettsii.
The flow and spatial dispersion of human visceral leishmaniasis from 2005 to 2015 in the RRAS11 mesoregion. The colors represent the year in which the first case of VL was detected and the numbers represent the municipality where the patients live or have been referred from. The lines represent the flow of the disease
Table 1 Laboratory parameters at presentation, clinical profile, and findings
On May 28, 2009, a 13-month-old boy residing in Tupi Paulista municipality (Fig. 1, number 2) was admitted with fever, inappetence, and splenomegaly. On systematic examination, he was pale and febrile with a distended abdomen and hepatosplenomegaly. Because he lives in an endemic area, VL was suspected and bone marrow aspirate examinations were conducted according to the laboratory diagnostics recommended by the Manual of Surveillance and Control of Visceral Leishmaniasis of São Paulo state [8] (Table 1, column 2). At diagnosis, his laboratory results were as follows: total protein 6.8 g/dL, albumin 3.6 g/dL, globulin 3.2 g/dL, and A:G ratio of 1.1 with a 2-fold increase and 12-fold increase in IgG and IgE immunoglobulin levels, respectively. Serum protein electrophoresis revealed polyclonal hypergammaglobulinemia: total protein 7.3 g/dL, albumin 3.95 g/dL, alpha1-globulin 0.41 g/dL, alpha2-globulin 0.76 g/dL, beta1-globulin 0.43 g/dL, beta2-globulin 0.23 g/dL, gamma-globulin 1.53 g/dL (20.9%; reference 10.6%–18.8%). He was treated with liposomal amphotericin B (5 mg/kg/day) for 5 days with improvement in the symptoms and 50% reduction of splenomegaly. CMV IgG and IgM antibodies were detected in the serology screening. After 8 days, he was discharged with a diagnosis of VL-CMV co-infection. However, the patient had a relapse several times at 59 days, 79 days, and 156 days after discharge. On each recurrence, he was admitted to the pediatric ward and underwent the standard treatment for 5 days. After the last infection, he was treated with an HIV-positive immunosuppressed regimen (liposomal amphotericin B, 5 mg/kg/day, 1 day per month for 6 months). A primary immunodeficiency was investigated and immunophenotyping and lymphocyte proliferation were at normal levels (Table 2, column 1). At discharge, he was diagnosed as VL-CMV co-infection and treated with an immunosuppressed regimen. After treatment, immunoglobulin and serum protein electrophoresis showed normal levels. After this protocol, he did not relapse and was followed for 1 year as an ambulatory patient with pediatric infectious diseases.
Table 2 Immunological markers of the patients at presentation and at follow-up
On November 13, 2014, a 14-month-old girl residing in Ouro Verde municipality (Fig. 1, number 3) was referred from Dracena's municipal hospital; her parents related that she had been vomiting and had had a fever for 9 days. VL was suspected and bone marrow aspirates, IFAT and rK39 were conducted according to the laboratory diagnostics recommended by the Manual of Surveillance and Control of Visceral Leishmaniasis of São Paulo state [8] (Table 1, column 3). On systematic examination, her health status was regular, but she was pale (1+/4+), with a distended abdomen and hepatosplenomegaly (Table 1, column 3). She was treated with liposomal amphotericin B (5 mg/kg/day) for 5 days and was found to have severe anemia. Red blood cells (15 mL/kg/day) were transfused twice, and the patient was discharged 15 days later with a diagnosis of VL. However, the patient had a relapse several times at 98 days, 131 days, 156 days, and 171 days, with the same symptoms at different time intervals. On each recurrence, she was admitted to the pediatric ward and underwent the standard treatment for 5 days. After the last hospitalization (at 171 days), she was treated with an HIV-positive immunosuppressed regimen (liposomal amphotericin B, 5 mg/kg/day, 1 day per month for 6 months). A primary immunodeficiency was investigated and immunophenotyping showed normal levels, however a decrease in lymphoproliferation against mitogens and CMV antigen was found (Table 2, column 2). In the course of the relapse treatment, she had multiple upper airway infections (community-acquired pneumonia, tonsillitis, and sinusitis). Specific antibody responses to pneumococcal polysaccharide vaccine (representing a T cell- independent response) and tetanus, diphtheria, and hepatitis B virus after vaccination (representing a T cell-dependent response) were investigated. The concentration of antibodies was below protective levels after vaccination. Furthermore, the patient showed a poor polysaccharide antibody response to a 23-valent pneumococcal vaccine. After completing the immunosuppressed regimen, she did not relapse, and she is being followed as an ambulatory patient with pediatric infectious diseases and immunodeficiencies.
On November 23, 2010, a 8-month-old boy referred from Dracena's municipal hospital (Fig. 3, number 4) was admitted to RH with fever, cough, and vomiting for the previous 5 days. On systematic examination, he was pale, febrile, dehydrated with tachydyspnea, distended abdomen, and hepatosplenomegaly. He was sent to the pediatric ICU and treated for community-acquired pneumonia. Because he lives in an endemic area, VL was suspected and bone marrow aspirate examinations were conducted according to the laboratory diagnostics recommended by the Manual of Surveillance and Control of Visceral Leishmaniasis of São Paulo state [8]. (Table 1, column 4). He was treated with liposomal amphotericin B (5 mg/kg/day) for 5 days. Immunoglobulin levels were determined, resulting in pan-hypogammaglobulinemia. Immunophenotyping and lymphocyte proliferation were investigated, and he was diagnosed as X-linked agammaglobulinemia (XLA). Patients with XLA have absent or reduced number of peripheral B cells and a profound deficiency in all immunoglobulin isotypes (Table 2, column 3). He was discharged after 20 days, and he is being followed as an ambulatory patient with immunodeficiencies with human IgG immunoglobulin (400 mg/kg) replacement at intervals of 28 days.
In 2011, a 11-year-old girl, residing in Paulicéia municipality (Fig. 3, number 5), was admitted to RH (personal data [12]). She was AIDS-C3 with low levels of CD4, high viral load, severe diarrhea, oral and perineal candidiasis, severe thrombocytopenia, and protein-caloric malnourishment. She had sepsis and renal and cardiac failure. She was sent to the pediatric ICU, and because she lives in an endemic region, VL was suspected. Bone marrow aspirate examinations according to the laboratory tests recommended by the Manual of Surveillance and Control of Visceral Leishmaniasis of São Paulo state were conducted [8] (Table 1, column 5). Her symptoms improved significantly after administration of liposomal amphotericin B. However, on the 47th day of hospitalization, she had a relapse with thrombocytopenia and retreatment with liposomal amphotericin B and intravenous human IgG immunoglobulin was given. She was discharged after 71 days, diagnosed as VL-HIV/AIDS co-infection. The patient was lost to follow-up.
Discussion and conclusions
American Tegumentar Leishmaniasis (AT) and VL are found in all regions of Brazil. The main causative agents of AT are Leishmania (Leishmania) amazonensis, Leishmania (Viannia) guyanensis, and Leishmania (Viannia) braziliensis which is responsible for the muco-cutaneous form in São Paulo state. Countrywide, Leishmania infantum (syn. Leishmania chagasi) is the causative agent of VL, and it is found especially in dogs (the main domestic reservoir), in cats and in humans [9,10,11]. Using different independent molecular methods, the genetic diversity of L. infantum isolates obtained from different endemic areas in Brazil revealed 18 very similar genotypes [11].
Despite the measures adopted by public authorities to control VL throughout São Paulo state, there is evidence that the disease is spreading at an alarming rate throughout the western region [4, 12, 13]. Since 2009, RH has been a reference center for the diagnosis and treatment of children thought to be infected with VL in the RRAS11 region. From January 2005 to December 2017, 157 children have been diagnosed and treated.
VL is an immune-mediated disease affecting mostly children because of their immature cell-mediated immune system, the cornerstone effector mechanism in VL infection, and older people as a result of senescence [4,5,6,7,8,9,10,11,12]. Among the patients selected for this study, four (80%) showed immune deregulation at diagnosis or during follow-up.
Case 1 involved co-infection with VL and dengue virus, both blood-borne diseases with a biological cycle in the liver and liver dysfunction. In patients infected with VL, a good prognosis is associated with reduction in the effects on the liver and spleen by 50% from onset to discharge and a decrease or normalization of the hepatic enzymes at the end of treatment [14, 15]. The cells of the reticuloendothelial system in the liver harbor VL parasites, and hepatomegaly is common. In India, functional derangement of the liver in individuals infected with VL was found to be common [16]. Surprisingly, in our patient, at the end of treatment for VL, she had severe liver injury, and dengue IgM serology confirmed VL-dengue virus co-infection. Liver involvement in acute dengue infection is frequently observed, leading to liver dysfunction. The severity depends on hypoxic injury as a result of decreased perfusion, the degree of viral load, and the deregulated immunologic lesions triggered by inflammatory immune mediators [17]. The spectrum of involvement ranges from asymptomatic increased levels of hepatic enzymes to acute liver failure. As in our patient, in children infected with dengue, increased AST/ALT levels, hepatomegaly, jaundice, and hypoalbuminemia are the main features. In Thailand and in Northern India, dengue was the major cause of acute liver failure in children with rates of 18.5 and 34%, respectively [17, 18]. However, to our knowledge, a VL-dengue co-infection has not been described previously.
Cases 2 and 3 were characterized by relapses with repeated treatments with liposomal amphotericin B. Following the Manual of Surveillance and Control of American Visceral Leishmaniasis of the State of São Paulo [8], the use of amphotericin B is restricted to a few special conditions. In 2006, in an effort to lower death rates from VL, especially in children, attributed to the use of pentavalent antimony as first-line therapy, São Paulo state recommended liposomal amphotericin B therapy for all children up to 10 years of age [19]. Relapse after treatment with liposomal amphotericin B is associated with increased lethality rates, poor prognosis, and disease severity among children [14, 20]. Little is known regarding the characteristics of apparently immunocompetent patients with VL who relapsed among different regions, treatment regimens, and study populations. In the Brazilian guidelines, there are no instructions on how to manage these patients. In Sudan, relapsed patients showed splenomegaly at diagnosis and at discharge [15, 21]; in Georgia, delay in the diagnosis for > 90 days, low levels of hemoglobin, and age < 1 year [22]; in India, male sex, aged 5–45 years, a smaller decrease in splenomegaly at discharge, and a shorter duration of symptoms before seeking treatment were strongly associated with relapse [14]. In patients with acquired immunodeficiency, mostly patients with HIV infection, the burden of VL infection and relapse is aggravated by impaired T cell number and function and, consequently, decreased T and B cell interaction [23, 24]. In an attempt to find the primary immunodeficiency that explained the increased number of relapses in our patients, immunophenotyping, lymphocyte proliferation, and humoral response against vaccines were conducted. A normal range of peripheral immune cells was found in both patients, however, patient 3 (Table 2, column 2) showed a decrease in lymphoproliferation against OKT3 (anti-CD3) mitogen and CMV antigen. Furthermore, she did not respond to T cell-dependent vaccines, anti-HBS and anti-tetanus, or to T cell-independent pneumo-23 polysaccharide vaccines. These results explain in part the repeated upper airways infections that affected the patient during treatment with liposomal amphotericin B in the relapsing period. Conversely, at onset of diagnosis of VL, patient 2 (Table 2, column 1) showed polyclonal gammopathy with increased levels of IgG and IgE and a slight hypergammaglobulinemia that quickly decreased to normal levels after treatment. Both patients recovered when the protocol for secondary prophylaxis to immunosuppressed patients was applied. Patients 2 and 3 required great effort from our team who contacted many other hospitals and doctors to discuss the drug and the duration of treatment to be adopted. Currently, a new protocol addressing these issues is being proposed in the state of São Paulo. Increasing rates of relapse against liposomal amphotericin B, the standard treatment for children, are occurring in our region. Of 157 children treated, 15 have relapsed (9.5%).
Case 4 arrived in the emergency room with fever, tachydyspnea, and cough, and community-acquired pneumonia associated with VL was diagnosed. Certainly, the undiagnosed primary immunodeficiency contributed to the severity of his condition. XLA deficiency is caused by mutations of the Bruton tyrosine kinase gene and is the most common form of severe inherited antibody deficiency. It is characterized by a fully penetrant X-linked recessive disorder with recurrent bacterial infections, including upper and lower airways infections, profound hypogammaglobulinemia, and marked decrease or absence of peripheral mature B cells [25]. As shown in Table 2, column 3, he exhibited normal levels of T cell subsets and lymphocyte proliferation against mitogens. However, total depletion of CD19+ B cells, no antibody response to vaccine antigens, representing a decrease in a B and T cell-dependent response, and hypogammaglobulinemia were found. He was not receiving intravenous immunoglobulin replacement therapy at the diagnosis of VL. To our knowledge, this is the first report of VL-XLA infection worldwide.
Case 5 represents an unwelcome synergy and was the first case of a child co-infected with HIV/AIDS and VL described in the western region of São Paulo state [12]. In Brazil, from January 1980 to June 2016, 842,710 cases of AIDS were reported, and the rate of detection of AIDS in children < 5 years of age has been used as a proxy indicator for monitoring the vertical transmission of HIV, with a local and countrywide reduction [26,27,28]. HIV-VL co-infection is considered an emerging disease in some developed and developing countries, with increasing rates since the beginning of the 1990s. The burden of the disease is fueled by geographic superposition of the two infections as a consequence of the urbanization of VL and the internalization of HIV infection [28, 29]. Previously, VL was restricted to rural areas in the northeastern region, responsible for 70–90% of cases, but since the 1980s, the formation of shantytowns with very poor living conditions favored important outbreaks in large Brazilian cities. Conversely, as a result of the countrywide spread of HIV infection in all social classes, outbreaks have moved from large urban centers to the smaller towns [28,29,30]. This new scenario represents a challenge for the control of HIV-VL co-infection [23]. In Brazil, HIV-VL co-infection has increased from 0.7% in 2001 to 8.5% in 2012 [23, 24]. HIV/AIDS is burdensome for children co-infected with VL, with decreasing anti-leishmania antibodies titers and therapeutic response, increasing susceptibility to severe hospital-acquired infections, greatly increased probability of relapse, and high mortality rates [12, 23, 24, 30]. The onset of clinical manifestations, diagnosis, and treatment of VL and discharge of the patient at 71 days was longer than usual in children treated in RH. In new endemic areas, lack of awareness of the occurrence of unusual manifestations may cause considerable difficulties in establishing the diagnosis [4, 12], and should be considered the reason for the delay in the diagnosis of VL in this case report.
In these selected case reports, 50% were associated with viral infections: CMV, dengue, and HIV. Co-infection of CMV with leishmaniasis produces a diagnostic dilemma because of the similarity of some clinical features and hematologic parameters, including fever, leukopenia, and thrombocytopenia [31]. Moreover, CMV infection has an immunomodulating and immunosuppressant effect on humoral and cellular immune responses, predisposing the patient to other infections. CMV may also be part of the super-infections reported in patients with VL [32].
Three (60%) of our patients were referred from other hospitals, and three (50%) were sent from the emergency room to the ICU because of worsening of their clinical status, reinforcing the role of tertiary hospitals in the Brazilian public health system and fueled by the severity of unusual manifestations of VL.
São Paulo state has experienced a rapid spread of the vector and canine and human VL over the last two decades, and some regions, including the western region, are becoming new endemic areas in Brazil [4, 13]. In this region, the epicenter of the infection was in the northern part, with clusters of municipalities harboring higher numbers of cases (48–153), bordered by municipalities with a medium (14–36) and low number of cases (1–4), in 2005–2015 (Fig. 2). These municipalities, are linked by contiguity to the municipality of Andradina, outside RRAS11 and considered endemic by the Brazilian Ministry of Health since 2005 [4, 12, 13] (Fig. 3). All children in this report lived in municipalities in which the disease was first described in 2005–2006. Cases 1 and 4 lived in Dracena, case 2 in Tupi Paulista, case 3 in Ouro Verde, and case 5 in Paulicéia (Figs. 1 and 2). With the exception of Paulicéia, the other municipalities registered medium or high number of cases in 2005–2015 (Fig. 2). From Dracena, the disease spread toward the north and then toward the municipalities of Pontal of Paranapanema, the poorest and most undeveloped region of São Paulo, and toward Paraná state in the south (Figs. 1 and 3). Considering these results, a spatial-temporal geographic occurrence in the spread of VL was found in the western region of São Paulo state.
Geographical distribution of human visceral leishmaniasis in the RRAS11 mesoregion, between 2005 and 2015. The colors represent the accumulative numbers of cases
Geographic location of São Paulo state, Brazil, and the study area. The mesoregion of Presidente Prudente, within RRAS11, and the neighboring states of Mato Grosso do Sul (MS), and Paraná (PR) and the network of highways linking different municipalities. The 33 municipalities of Pontal of Paranapanema are in RRAS11. Paraná River on the border of MS and Paranapanema River on the border of PR with lakes supporting hydroelectric plants and bridges. Data were obtained from the Brazilian Institute of Geography and Statistics
The reasons why VL is spreading in such a fast and alarming way in this region are not well understood. A complex array of factors may be fueling the epidemic and sustaining endemic transmission [4]. In São Paulo state, the association of the spread of VL throughout the area around the Marechal Candido Rondon Highway, the Bolivia-Brazil railway, and the gas pipeline construction (GASBOL), linking the endemic region of Mato Grosso state in direction of São Paulo, is overwhelming [3] (Fig. 3). Similarly, we suggest that in RRAS11, the dispersion of canine VL and human VL vectors is associated with the Euclides Figueiredo Highway as the primary axis, and the Julio Budinsky Highway as the secondary axis. Nevertheless, dissemination of the vectors of VL could be aggravated by the extensive watershed flowing into the three biggest rivers of southwestern and southern Brazil, with nine large lakes and a flooded area of 2384 mile2, supporting hydroelectric plants and bridges. These bridges link dozens of small towns and villages connected by a large number of highways (1480 miles). They support a daily flow of people, cars, animals, and goods linking endemic regions to VL-free areas (Fig. 3).
Some shortcomings should be mentioned when interpreting our data. This is a retrospective study over 10 years with selection bias as a result of different investigators. The protocol for VL diagnosis changed during the study period and immunophenotyping and lymphocyte proliferation were not available for all patients.
Primary and secondary immunodeficiencies and viral co-infections should be considered among unusual manifestations of VL, especially in those with multiple relapses. In this scenario, tertiary reference hospitals have a key role in the Brazilian public health system. In the geographic spread of VL, a higher number of cases were demonstrated in the northern part, in the epicenter of the area where the first cases were registered, flowing to the south and a spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.
ALT:
AST:
Aspartate transaminase
CMV:
HIV/AIDS:
Human immunodeficiency virus/acquired immunodeficiency syndrome
ICU:
RH:
Regional Hospital of Presidente Prudente
RRAS11:
Regional Health Assistance Network11
VL:
Visceral leishmaniasis
XLA:
X-linked agammaglobulinemia
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No funding support was received.
All data generated or analyzed during this study are included in this article.
Infectious Diseases and Immunology Department, Oeste Paulista University, Presidente Prudente, São Paulo, Brazil
Luiz Euribel Prestes-Carneiro & Francisco Assis da Silva
Pediatrics Department, Oeste Paulista University, Presidente Prudente, São Paulo, Brazil
Patricia Rodrigues Naufal Spir
Imunodeficiencies Outpatient Clinic, Pediatrics Outpatient Clinic, Regional Hospital of Presidente Prudente, Presidente Prudente, São Paulo, Brazil
Luiz Euribel Prestes-Carneiro, Patricia Rodrigues Naufal Spir, Mateus Fontanesi & Karen Gabriella Pereira Garcia
Statistics Department, Paulista State University, Presidente Prudente, São Paulo, Brazil
Edilson Ferreira Flores
Laboratory of Medical Investigation Unit 56, Hospital das Clınicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
Dewton de Moraes Vasconcelos
Luiz Euribel Prestes-Carneiro
Mateus Fontanesi
Karen Gabriella Pereira Garcia
Francisco Assis da Silva
LEPC, PRNS, and DMV designed the study. LEPC wrote the paper. PRNS, MF, and KGPG evaluated and treated the patients. PRNS and LEPC undertook follow-up of the patients and supplied the clinical data, LEPC, FA, and EFF conducted the statistical analysis and constructed the maps. All authors reviewed and approved the final version of the paper submitted to the journal.
Correspondence to Luiz Euribel Prestes-Carneiro.
The study was approved by the research ethics committee at Universidade do Oeste Paulista and Plataforma Brasil (certificate of ethical approval protocol number 2.127.403). Written informed consent was obtained from the parents of the reported cases for this paper to be published.
Written informed consent was obtained from the guardians of patients described in these case reports. A copy of the written consent is available for review by the Editor of this journal.
Prestes-Carneiro, L.E., Spir, P.R.N., Fontanesi, M. et al. Unusual manifestations of visceral leishmaniasis in children: a case series and its spatial dispersion in the western region of São Paulo state, Brazil. BMC Infect Dis 19, 70 (2019). https://doi.org/10.1186/s12879-018-3652-1
Unusual manifestations, spatial dispersion
Parasitological diseases


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Example of an easy jewelry box woodworking plan.
This is one the classic, simple and elegant piece of jewelry boxes that you can find. Hand cut mitered dovetails are used here which gives the design its subtlety. Check this this plan which comes from none other than the prestigious woodworking magazine here.
If you want a sophisticatedly designed jewelry box, this piece is definitely going to catch your fancy. The best thing about this plan is that with just a table saw you can carry out most of the joinery tasks. And we need not say that the end result is beautiful. Get the plan here.
If you would like a jewelry box that comes with drawers, this is the one to go for. The plan gives the details of how much material you will need, the tools you will need along with all the necessary instructions and step by step pictures.
This is a bit of an advanced jewelry box plan that has its share of twist – it boasts of a shelf that rises with the lid. If you think that a removable shelf makes the task of taking out jewelry cumbersome, this box will suit your needs most. When you open the lid of this box, the shelf does not just rise up on its own, it also serves as a means to hold the lid. It is definitely one ingenious piece of woodwork. Check out the details of the project here.
Whenever you set out to make a jewelry box, make sure that you make more than one. They are ideal to gift to your mother on her birthday or to your spouse on Valentine's Day – of course you might need to gift her some jewelry as well.